The value of M&A deals in the biopharmaceutical industry increased in 2023 and that trend is anticipated to maintain its course during 2024. Higher-value transactions are expected to be targeted by big pharma players as companies look for ways to address the growth concerns ahead of them due in part to patent cliffs and the impact of the Inflation Reduction Act.
“2023 was a reasonably strong year for the pharmaceutical and life sciences sector with both deal value and volume of M&A close to pre-pandemic levels,” according to PricewaterhouseCoopers’ (PwC) “Pharmaceutical and life sciences: US Deals 2024 outlook” report. “In 2024, we expect similar levels of activity, in the $225 billion to $275 billion range across all subsectors. Executives will continue to deploy cash balances and seek out areas of innovation and clinical differentiation to help address remaining growth challenges in the latter half of the decade.”
The PwC report shows that pharmaceuticals and life sciences (PLS) deal values in 2023 increased 50 percent compared to the prior calendar term, reaching $237.6 billion. The 268 transactions in 2023 represented a year-over-year increase of 4 percent. Leading the way was Pfizer Inc.’s acquisition of Seagen Inc. for $43 billion, a deal that was completed by the biopharma behemoth in December. This was the largest transaction in the pharma space since 2019 when Abb-Vie Inc. acquired Allergan plc for $63 billion. The next largest deal in 2023 was Bristol Myers Squibb Co.’s December purchase of Karuna Therapeutics Inc. for a total equity value of $14 billion.
According to Evaluate Ltd.’s 2023 Review report, biopharma M&A deals totaled $153.4 billion last year, the largest tally since before the COVID-19 pandemic. The biopharma industry generated $239.2 billion in acquisitions during 2019, $131 billion during 2020 when the pandemic took hold, and $90-plus billion in each of 2021 and 2022. Evaluate reported that biopharma deal volume in 2023 amounted to 135 M&A pacts, up from 126 transactions during 2022.
“Despite some stabilization in the macroeconomic environment and the potential for a soft landing in sight, continued geopolitical and regulatory uncertainty seems a given in 2024,” the PwC report noted. “Against this backdrop – and coupled with the reality of higher interest rates – we expect dealmakers to increasingly focus on margin accretion in M&A, rather than relying prominently on growth-driven dealmaking. As regulators’ perspectives on key deal factors become better understood, there may be a return of larger deals, along with continued interest in the $5 billion to $15 billion deals to fill targeted strategic gaps.”
Industry trackers at PwC say the stakes for M&A for the pharma sector will be even higher in 2024. “The competition for high-quality assets will remain incredibly fierce and the regulatory landscape remains challenging. It will be critical that companies invest appropriately in a multi-pronged, technologically enabled and agile inorganic strategy. Companies taking a multi-faceted and capability-driven approach, wedding the ‘not innovated here’ and ‘innovated here’ approaches, will emerge in a stronger position. The traditional M&A approaches that got us here will not be the strategies that get us to tomorrow. We expect an increasing focus in M&A on delivering margin accretion.”
On the technology front, pharma companies are employing AI for various reasons, including finding patients for studies more quickly and to cut down on the amount of individuals necessary to test products. These actions will help speed up the development process for new medicines while offering drugmakers the potential to saves millions of dollars.
According to the U.S. Food and Drug Administration, the regulatory agency received about 300 marketing applications that incorporate AI or machine learning in drug development from 2016 through 2022. More than 90 percent of those applications were filed during the 2021-2022 period, and most were for the use of AI at some time during the drug development phase.
Model N Inc.’s sixth annual State of Revenue Report revealed life sciences and high-tech executives’ top business priorities and challenges. The 2024 report cited process efficiency and cost-saving measures as priorities for executives, with greater emphasis placed on advanced analytics and artificial intelligence (AI) to achieve these priorities. In terms of process efficiencies, three-quarters of surveyed executives said their current approach to revenue optimization needs improvement, and survey responses demonstrated plans to strengthen revenue operations by incorporating advanced analytics (68 percent), AI (59 percent), and robotic process automation (46 percent).
“AI and analytics are ushering in a new era of revenue optimization and compliance across the life sciences and high-tech industries,” stated Model N Chief Strategy and Marketing Officer Rehmann Rayani. “Outdated, manual, and/or patchwork sales and revenue processes can undermine profitability for even the most innovative companies, and new technologies will unlock data-driven insights that manufacturers need to maximize revenue and remain compliant.”
Quant Health CEO and Co-founder Orr Inbar said 2024 will be the year that AI integration will be pivotal to the continued success of those working throughout biotech and life sciences, especially for those involved in the drug discovery and regulation processes. “I anticipate we’ll begin to see a significant drop in clinical trial failure rates, a $45 billion a year issue, and this will have a duel impact of not only saving money for those looking to bring new therapies to market but also allowing these companies to take more shots on goal with the peace of mind of having a solid sense of how the clinical trials that they choose to move forward with will work out before they even get started,” Inbar told Med Ad News.
According to PwC’s analysis, differentiated science and clinical advances continue to come in waves, and the analysts anticipate seeing dealmaking in areas with meaningful incremental innovation during 2024. “Pharma and biotech dealmaking will continue to focus on precision medicine in areas such as oncology and immunology, but we also expect to see a heightened focus on weight loss and cardiovascular, a therapeutic area that went through a renaissance in 2023.”
Several companies featured in Med Ad News’ annual pipelines report have recently struck deals for clinical assets that target the anti-obesity market – looking to capitalize on the massive success generated by Novo Nordisk A/S and Eli Lilly and Co. in that category – including Pfizer, Roche and AstraZeneca plc.
ASTRAZENECA
AstraZeneca’s pipeline consisted of 167 projects as of November 2023, including 14 new molecular entities in late-stage development and three NMEs undergoing regulatory review. Among the NMEs industry analysts are excited about is datopotamab deruxtecan (Dato-DXd), an investigational TROP2-directed antibody-drug conjugate (ADC) being developed with Daiichi Sankyo Co.
Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Dato-DXd is one of six lead ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Dato-DXd is composed of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
“With the potential to become the best-in-class TROP2-targeted ADC, datopotamab deruxtecan is set to be second to market (after Gilead Sciences Inc.’s Trodelvy) for both HR-positive/HER2-negative and triple-negative breast cancer, and to enter the non-small cell lung cancer (NSCLC) market,” according to analysis from Clarivate’s 2024 Drugs to Watch report.
A comprehensive development program called TROPION with more than 12 studies worldwide is assessing the efficacy and safety of Dato-DXd across multiple tumors, including non-small cell lung cancer, triple-negative breast cancer (TNBC) and hormone receptor-positive, HER2-low or negative breast cancer. Dato-DXd is also being explored in novel combinations in several studies. AstraZeneca is additionally investigating a potential diagnostic test to help identify patients most likely to benefit from treatment with datopotamab deruxtecan.
To further build the company’s R&D coffer, AstraZeneca agreed to acquire Gracell Biotechnologies Inc. and Icosavax Inc. during December 2023. The transaction with Gracell will further AstraZeneca’s cell therapy ambition across oncology and autoimmune diseases. Building on expertise in respiratory syncytial virus (RSV) prevention, the Icosavax acquisition will accelerate AstraZeneca’s ambition to deliver a portfolio of protective interventions to address high unmet needs in infectious diseases.
The global clinical-stage biopharmaceutical company Gracell is developing innovative cell therapies for treating cancer and autoimmune diseases. The acquisition is anticipated to enrich AstraZeneca’s growing pipeline of cell therapies with GC012F, a novel, clinical-stage FasTCAR-enabled BCMA and CD19 dual-targeting autologous chimeric antigen receptor T-cell (CAR-T) therapy, a potential new treatment for multiple myeloma (MM), and other hematologic malignancies and autoimmune diseases such as systemic lupus erythematosus.
Icosavax is a U.S.-based clinical-stage biopharma company concentrated on developing differentiated, high-potential vaccines using an innovative, protein virus-like particle (VLP) platform. The acquisition will build on AstraZeneca’s expertise in RSV, bolstering the company’s Vaccines & Immune Therapies late-stage pipeline with Icosavax’s lead investigational vaccine candidate, IVX-A12. A potential first-in-class, Phase III-ready, combination protein VLP vaccine, IVX-A12 targets RSV and human metapneumovirus (hMPV), two leading causes of severe respiratory infection and hospitalization in adults 60 years of age and older and those with chronic conditions including cardiovascular, renal and respiratory disease. There are no available treatments or preventative therapies for hMPV and no RSV combination vaccines.
AstraZeneca during November 2023 received U.S. marketing clearance for a first-in-class AKT inhibitor that has the potential to reshape treatment for breast cancer patients with specific biomarker alterations (PIK3CA, AKT1 or PTEN). Truqap (capivasertib) in combination with the company’s former blockbuster product Faslodex (fulvestrant) won FDA approval for the treatment of adults with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer with one or more biomarker alterations (PIK3CA, AKT1 or PTEN).
Wainua (eplontersen) was granted the product’s first FDA approval in December for treating adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis. The U.S. marketing clearance is based on NEURO-TTRansform Phase III results demonstrating Wainua showed consistent and sustained benefit improving neuropathy impairment and quality of life.
Launched in January 2024, Wainua represents the first approved medicine for treating ATTRv-PN that can be self-administered via an auto-injector. As part of a worldwide development and commercialization agreement, AstraZeneca and Ionis Pharmaceuticals Inc. are marketing Wainua for the treatment of ATTRv-PN in the United States and seeking regulatory clearance in Europe and other regions.
Eplontersen is being investigated in the CARDIO-TTRansform Phase III study for the treatment of transthyretin-mediated amyloid cardiomyopathy (ATTR-CM), a systemic, progressive, and fatal condition that typically results in progressive heart failure and often death within three-to-five years from disease onset.
AstraZeneca reported positive results in January from the EMERALD-1 Phase III study demonstrating Imfinzi (durvalumab) in combination with TACE (transarterial chemoembolization) and bevacizumab showed a statistically significant and clinically meaningful improvement in the primary endpoint of PFS versus TACE alone in patients with hepatocellular carcinoma (HCC) eligible for embolization. EMERALD-1 marks the first worldwide Phase III study to demonstrate improved clinical outcome for systemic therapy in combination with TACE in this setting.
Positive results from the 24-week and long-term extension (LTE) period of the pivotal ALPHA Phase III study showed the investigational oral medicine danicopan as add-on to the standard-of-care C5 inhibitor therapy Ultomiris (ravulizumab) or Soliris (eculizumab) continued to demonstrate clinical benefit for patients with paroxysmal nocturnal hemoglobinuria (PNH) who experience clinically significant extravascular hemolysis (EVH). The product has been granted Breakthrough Therapy Designation and Orphan Drug Designation in the United States for treating PNH. Alexion – the group within AstraZeneca focused on rare diseases that brought to market Ultomiris and Soliris – is additionally assessing danicopan as a potential monotherapy for geographic atrophy in a Phase II study.
Enhertu (trastuzumab deruxtecan) received FDA Priority Review during the end of January for patients with metastatic HER2-positive solid tumors. If cleared for marketing, AstraZeneca and Daiichi Sankyo’s Enhertu will potentially be the first HER2-directed treatment and antibody drug conjugate to gain a tumor-agnostic indication. The specifically engineered HER2-directed ADC is being jointly developed and marketed by AstraZeneca and Daiichi Sankyo.
The blockbuster brand Enhertu is commercialized globally for treating forms of breast cancer, non-small cell lung cancer, and gastric or gastroesophageal junction (GEJ) adenocarcinoma. Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program within AstraZeneca’s ADC scientific platform. Enhertu is composed of an HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads via tetrapeptide-based cleavable linkers.
AstraZeneca presented new clinical and real-world data in multiple hematological conditions at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition in December 2023. Data from the company’s early portfolio showed how AstraZeneca is advancing multiple modalities across several scientific platforms, including immuno-oncology, immune-engagers, ADCs, and epigenetics as part of AZ’s strategy to attack cancer from multiple angles.
AstraZeneca Senior VP, Hematology R&D, Anas Younes stated: “Our data at ASH exemplify how we are advancing a range of innovative modalities including ADCs, next-generation
immunotherapies and T-cell engagers in hematology. Updated clinical data for AZD0486, our CD19/CD3 T-cell engager, reinforce our belief in this approach as a potential new treatment for lymphoma, and new Calquence data continue to demonstrate long-term efficacy and safety in chronic lymphocytic leukemia with further follow up.”
AstraZeneca reached a deal with Eccogene in November to exclusively license a novel agent for treating cardiometabolic conditions and obesity. ECC5004 is an investigational oral once-daily glucagon-like peptide 1 receptor agonist (GLP-1RA) intended as a treatment for obesity, type 2 diabetes, and other cardiometabolic conditions.
AZ’s Executive VP, BioPharmaceuticals R&D, Sharon Barr commented: “Building on the promising Phase I clinical data generated by Eccogene, we believe this oral GLP-1RA molecule could offer alternatives to current injectable therapies both as a potential monotherapy as well as in combination for cardiometabolic diseases such as type 2 diabetes, as well as for obesity. ECC5004 further strengthens our existing pipeline addressing both incretin and non-incretin pathways, including our GLP-1/glucagon dual agonist [AZD9550] and long-acting amylin analog [AZD6234].”
AstraZeneca launched during November Evinova, a health-tech business to accelerate innovation across the lifesciences sector, the delivery of clinical studies and better health outcomes. With long-term backing from AstraZeneca and strategic collaborations with Parexel and Fortrea Inc., Evinova offers worldwide-scaled digital products and services to the life sciences and healthcare arena.
Evinova will prioritize bringing to market established and scaled digital technology solutions already being used around the world by AstraZeneca to optimize clinical study design and delivery. This will cut down on the time and cost of developing new medicines, bring care closer to home for patients and reduce the burden on health systems. Evinova will also pursue opportunities in digital remote patient monitoring and digital therapeutics with a pipeline of digital innovations in these areas.
BRISTOL MYERS SQUIBB
BMS made three recent acquisitions in a two-month span totaling $22.9 billion in combined deal value that will significantly solidify and expand the New York-based biopharma company’s already-strong pipeline arsenal.
BMS has bolstered the company’s neuroscience portfolio with the acquisition of Karuna, as announced on December 22, 2023. Karuna is being purchased for $330.00 per share in cash, for a total equity value of $14.0 billion, or $12.7 billion net of estimated cash acquired.
The biopharma company Karuna is driven to discover, develop, and deliver transformative medicines for people living with psychiatric and neurological conditions. Karuna’s lead asset is the antipsychotic KarXT (xanomeline-trospium), with a novel mechanism of action (MoA) and differentiated efficacy and safety. Karuna’s New Drug Application (NDA) for KarXT for treating schizophrenia in adults was accepted for review with a Prescription Drug User Fee Act (PDUFA) date of September 26, 2024. KarXT is additionally in registrational studies for adjunctive therapy to existing standard of care agents in schizophrenia and for treating psychosis in patients with Alzheimer’s disease. Management at BMS believes that KarXT represents a significant revenue contribution opportunity, and sees potential from Karuna’s early-stage and pre-clinical pipeline.
“There are tremendous opportunities in neuroscience, and Karuna strengthens our position and accelerates the expansion and diversification of our portfolio in the space. We expect KarXT to enhance our growth through the late 2020s and into the next decade,” said BMS CEO Christopher Boerner, Ph.D. “This transaction fits squarely within our business development priorities of pursuing assets that are strategically aligned, scientifically sound, financially attractive, and have the potential to address areas of significant unmet medical need.”
According to the company, given this differentiated profile, KarXT has meaningful and expanding revenue potential in schizophrenia and with upside in additional indications and geographies. KarXT is anticipated to launch during late 2024 in the United States as a treatment for schizophrenia in adults.
BMS completed the acquisition of Mirati Therapeutics Inc. in January 2024, a transaction that will bolster and diversify the company’s oncology portfolio. Through this deal, BMS has added the commercialized lung cancer medicine Krazati (adagrasib) to the company’s oncology portfolio as well as several promising clinical assets. The assets include a potential first-in-class MTA-cooperative PRMT5 inhibitor in Phase I development, and a leading KRAS and KRAS-enabling program with two candidates in Phase I studies.
The transaction was announced during October 2023, with BMS acquiring Mirati for $58 per share in cash, for a total equity value of $4.8 billion. “The closing of the Mirati transaction is a significant milestone in our efforts to further diversify our oncology portfolio and strengthen our pipeline in the latter half of the decade and beyond,” Dr. Boerner said.
BMS announced in December on the day after Christmas a deal to acquire the clinical-stage radiopharma therapeutics RayzeBio Inc. for $62.50 per share in cash, for a total equity value of $4.1 billion, or $3.6 billion net of estimated cash acquired. RayzeBio has an innovation-leading position in actinium-based RPTs and a pipeline of potentially first-in-class and best-in-class drug development programs. The company’s pipeline programs are focusing on treating solid tumors, including gastroenteropancreatic neuroendocrine tumors (GEP-NETs), small cell lung cancer, hepatocellular carcinoma and other cancers.
“This transaction enhances our increasingly diversified oncology portfolio by bringing a differentiated platform and pipeline, and further strengthens our growth opportunities in the back half of the decade and beyond,” Dr. Boerner said. “Radiopharmaceutical therapeutics are already transforming cancer care, and RayzeBio is at the forefront of pioneering the application of this novel modality.”
RayzeBio’s portfolio includes lead program RYZ101 (225Ac-DOTATATE), targeting somatostatin receptor 2 (SSTR2), which is over-expressed in GEP-NETs and extensive stage small cell lung cancer (ES-SCLC). A Phase III study is enrolling patients to assess RYZ101 in patients with SSTR-positive GEP-NETs who have previously been treated with lutetium-177 based somatostatin therapies. RayzeBio previously reported the interim results of the Phase Ib portion of the ACTION-1 study, suggesting encouraging efficacy and tolerability. A Phase Ib trial is additionally enrolling patients to investigate RYZ101 as a first-line treatment of ES-SCLC in combination with standard-of-care therapy.
SystImmune Inc. and BMS inked a deal in December to jointly develop and co-commercialize BL-B01D1 in the United States. SystImmune retained exclusive rights in Mainland China and BMS gained an exclusive license in the rest of the world. BL-B01D1 is a potentially first-in-class bispecific EGFRxHER3 ADC with the potential to treat patients with lung and breast cancer, with opportunities to expand into other tumor types.
U.S. regulators approved BMS’ Augtyro (repotrectinib) for treating adult patients with locally advanced or metastatic ROS1-positive NSCLC during November 2023. Administered as an oral therapy, the tyrosine kinase inhibitor (TKI) targets ROS1 oncogenic fusions.
BMS announced on January 30 three regulatory acceptances from the FDA and Japan’s Ministry of Health, Labour and Welfare (MHLW) for Breyanzi (lisocabtagene maraleucel). The U.S. drug regulator accepted BMS’ two supplemental Biologics License Applications (sBLA) for Breyanzi to expand into new indications to include the treatment of adults with relapsed or refractory follicular lymphoma (FL) and relapsed or refractory mantle cell lymphoma (MCL) after a Bruton tyrosine kinase inhibitor (BTKi). The FDA granted both applications Priority Review and assigned a PDUFA goal date of May 23, 2024 for Breyanzi in relapsed or refractory FL and May 31, 2024 for Breyanzi in relapsed or refractory MCL.
In relapsed or refractory FL, the filings for Breyanzi in the United States and Japan are based on data from the TRANSCEND FL trial, which represents the largest clinical study to date assessing a CAR T cell therapy in patients with relapsed or refractory indolent B cell non-Hodgkin lymphoma (NHL), including high-risk second-line FL. In relapsed or refractory MCL, the U.S. application is based on results from the MCL cohort of the TRANSCEND NHL 001 trial, in which Breyanzi showed statistically significant and clinically meaningful responses in heavily pre-treated patients, with the majority of patients achieving a complete response.
Subcutaneous nivolumab showed noninferior pharmacokinetics (co-primary endpoints) and objective response rate (key powered secondary endpoint) versus intravenous Opdivo in advanced or metastatic clear cell renal cell carcinoma in the CheckMate -67T study, according to results reported in January. CheckMate -67T represents the first Phase III study of the subcutaneous formulation of Opdivo to assess and show noninferior pharmacokinetics, efficacy, and safety compared to the product’s intravenous formulation. Data from the Phase III CheckMate -67T study were presented in a late-breaking oral presentation at ASCO GU 2024 in the first-ever disclosure for subcutaneous formulation of Opdivo.
One of the world’s top-selling pharma products, Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, the blockbuster medicine has become a significant treatment option across multiple cancers.
Results from the Phase III CheckMate -8HW study exploring Opdivo (nivolumab) in combination with Yervoy (ipilimumab) versus investigator’s choice of chemotherapy (mFOLFOX-6 or FOLFIRI with or without bevacizumab or cetuximab) as a first-line treatment for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC) were unveiled in January. The first presentation of results from the study demonstrates statistically significant and clinically meaningful improvement in progression-free survival with Opdivo plus Yervoy versus chemotherapy as first-line treatment in this patient population. Opdivo plus Yervoy represents the first dual immunotherapy regimen to show significant efficacy benefit versus chemo as first-line treatment in MSI-H/dMMR mCRC.
The blockbuster brand Yervoy is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). The FDA approved Yervoy 3 mg/kg monotherapy on March 25, 2011, for patients with unresectable or metastatic melanoma. The medicine is marketed for unresectable or metastatic melanoma in more than 50 countries. BMS says there is a broad, continuing development program in place for Yervoy spanning multiple tumor types.
BMS data reported at ASCO GU 2024 showcased transformative research in the treatment of genitourinary (GU) cancers. The first presentation of data from the Phase III CheckMate -67T study with subcutaneous formulation of Opdivo (nivolumab and Halozyme’s proprietary recombinant human hyaluronidase) were shared in a late-breaking oral presentation. BMS said four-year data from CheckMate -9ER and unprecedented eight-year data from CheckMate -214 confirmed durable outcomes with Opdivo-based combinations for patients with advanced renal cell carcinoma.
BMS and 2seventy bio Inc. released results from the preplanned final PFS analysis of KarMMa-3, the pivotal Phase III, open-label, worldwide, randomized controlled trial assessing Abecma (idecabtagene vicleucel) versus standard comb0 regimens in adults with relapsed and refractory MM after two to four previous lines of therapy, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 monoclonal antibody (triple-class exposed), who were refractory to their last regimen.
Abecma is the first-in-class B-cell maturation antigen (BCMA)-directed CAR T cell immunotherapy cleared for U.S. marketing as a treatment for adults with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an
anti-CD38 monoclonal antibody.
BMS revealed updated results at the 2023 ASH Annual Meeting from the primary analysis of the Phase III COMMANDS study, comparing Reblozyl (luspatercept-aamt) to epoetin alfa for treating anemia in erythropoiesis stimulating agent (ESA)-naïve patients with lower-risk myelodysplastic syndromes (MDS) who may require red blood cell (RBC) transfusions. The new data confirmed findings consistent with interim analysis, reaffirming superior efficacy and significantly longer durability of response with Reblozyl versus epoetin alfa.
The first-in-class therapeutic option Reblozyl promotes late-stage red blood cell maturation in animal models. The anemia product is being developed and commercialized through a worldwide collaboration and North American joint promotion with Merck & Co. following that company’s acquisition of Acceleron Pharma Inc. in November 2021.
Johnson & Johnson
J&J hosted a meeting on December 5, 2023, with the investment community at the New York Stock Exchange to present the company’s overarching strategy, diverse and robust Innovative Medicine and MedTech pipelines, and long-term financial outlook. “Science and technology will advance human health more in the next decade than it has in the last century, leading to more effective and personalized treatment, earlier intervention, and smarter, less invasive healthcare,” stated CEO Joaquin Duato. “We are excited to share today how the breadth of our scientific capabilities, diverse portfolio and robust pipelines uniquely position Johnson & Johnson to be a leader in this next wave of innovation while delivering strong financial performance.”
Johnson & Johnson continues to concentrate on areas of high innovation and higher growth while maintaining the company’s industry-leading pipeline, which is anticipated to deliver more than 20 novel therapies and 50-plus product expansions by 2030. By 2030, Johnson & Johnson’s Innovative Medicine pipeline and portfolio are projected to generate 5-7 percent operational sales growth from 2025-2030; 10-plus assets having the potential to deliver more than $5 billion in operational peak year sales (PYS), including the five assets highlighted during the 2021 Pharmaceutical Business Review as well as Talvey, Tecvayli and JNJ-2113; 15-plus assets having the potential to generate $1-$5 billion in operational PYS, including Spravato, seltorexant, aticaprant, and JNJ-4804.
Emerging from the J&J pipeline in January 2024 was a supplemental New Drug Application (sNDA) approval for Balversa (erdafitinib) as a treatment for adults with locally advanced or metastatic urothelial carcinoma ((la/mUC) with susceptible fibroblast growth factor receptor 3 (FGFR3) genetic alterations whose disease has progressed on or after at least one line of previous systemic therapy. This U.S. regulatory action converts the April 2019 accelerated approval of Balversa to a full approval based on the clinical and overall survival benefit observed in the Phase III THOR trial. Balversa represents the first oral FGFR kinase inhibitor to be approved, and the first targeted treatment for patients with mUC and FGFR alterations.
Seeking to advance next-generation antibody drug conjugates to transform the treatment of cancer, J&J during January agreed to acquire Ambrx Inc. The clinical-stage biopharma company has a proprietary synthetic biology technology platform to design and develop next-generation ADCs. The Ambrx transaction marks an all-cash merger deal representing a total equity value of $2 billion, or $1.9 billion net of estimated cash acquired.
Ambrx has been developing a concentrated portfolio of clinical and preclinical programs designed to optimize efficacy and safety of the company’s candidate therapeutics in multiple cancer indications. This includes: ARX517, a proprietary ADC targeting PSMA for metastatic castration-resistant prostate cancer (mCRPC); ARX788, a proprietary ADC targeting human epidermal growth factor receptor 2 (HER2) for metastatic HER2+ breast cancer; and ARX305, a proprietary ADC targeting CD-70 for renal cell carcinoma.
“Ambrx’s ADC technology offers unique advantages in the conjugation of stable antibodies and cytotoxic linker payloads, which results in engineered ADCs that effectively kill cancer cells and limit toxicities,” noted Yusri Elsayed, M.D., M.H.Sc., Ph.D., global therapeutic area head, oncology, Johnson & Johnson Innovative Medicine. “The results seen to date with ARX517 in mCRPC are promising and represent a potential first- and best-in-class targeted therapy for the treatment of this aggressive disease. In addition, Ambrx’s pipeline and ADC platform present exciting future opportunities to deliver enhanced, precision biologics as we look to transform the treatment of cancer and improve patients’ lives.”
J&J is seeking clearance via an sBLA and NDA for Rybrevant (amivantamab-vmjw) in combination with lazertinib for treating patients with epidermal growth factor receptor (EGFR)-mutated NSCLC. Submitted in December 2023 and based on the Phase III MARIPOSA trial, this represents the third regulatory filing from the Rybrevant clinical development program in four months, following sBLA submissions for MARIPOSA-2 and PAPILLON. During November, J&J reported the submission of an sBLA to U.S. regulators for Rybrevant in combination with chemotherapy (carboplatin and pemetrexed) for the treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions (ex19del) or L858R substitution after disease progression on or after osimertinib (branded as Tagrisso).
“The combination of Rybrevant and lazertinib demonstrated statistically significant and clinically meaningful improvement in progression-free survival compared to osimertinib in patients with previously untreated EGFR-mutated NSCLC. This remains an area of high unmet need as patients often experience treatment resistance and disease progression on currently available therapies,” stated Kiran Patel, M.D., VP, clinical development, solid tumors, Johnson & Johnson Innovative Medicine. “We believe this targeted, chemotherapy-free regimen may have the potential to transform the treatment of EGFR-mutated NSCLC.”
Janssen Pharmaceuticals Inc. reported new data in November 2023 from the CorEvitas Psoriatic Arthritis (PsA) and Spondyloarthritis Registry that demonstrated a substantial proportion of people living with treatment-resistant active PsA and using Tremfya (guselkumab) in real-world settings reported meaningful improvements in pain, physical function, and fatigue through six months. Across the DISCOVER-1, DISCOVER-2 and COSMOS Phase III studies, treatment with the blockbuster medicine was associated with higher rates of clinically meaningful improvements in a composite assessment of patient-reported pain, fatigue, physical function, skin problems and PsA-related depression than placebo in the first assessment of the PsA 5-Thermometer Scale Domains (PsA-5T-Ds).
New data were reported by Janssen in October 2023 from the QUASAR Phase III Induction Study showing the efficacy and safety profile of Tremfya in patients with moderately to severely active ulcerative colitis (UC) through 24 weeks. Developed by Janssen, Tremfya represents the first approved fully human monoclonal antibody that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor.
The company unveiled more than 85 presentations from J&J’s robust hematology portfolio and pipeline at the 65th ASH Annual Meeting. Clinical and real-world data highlighted J&J’s differentiated portfolio and pipeline across the spectrum of hematologic malignancies, further expanding the company’s leadership in multiple myeloma and B-cell malignancies and as a pioneer in the discovery and development of new therapeutic targets.
The late-breaking abstract session included the first presentation of results from the Phase III PERSEUS trial assessing a quadruplet regimen of Darzalex Faspro (daratumumab and hyaluronidase-fihj) and doublet maintenance regimen in treating patients with newly diagnosed multiple myeloma (NDMM) who are transplant-eligible (TE). The Darzalex Faspro data demonstrated an unrivaled PFS in a Phase III trial testing TE NDMM and clinically significant improvement of rates of overall complete response (CR) or better and minimal residual disease (MRD) negativity over the comparator arm.
At ASH, J&J announced new patient-reported outcomes (PRO) from the Phase III CARTITUDE-4 study of Carvykti (ciltacabtagene autoleucel; cilta-cel) showed clinically meaningful improvements in health-related quality of life and meaningful reductions in disease-specific symptoms according to multiple PRO measures in treating adult patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy (LOT). The product was the recipient of U.S. marketing clearance in February 2022 for treating adults with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including a PI, an IMiD agent and an anti-CD38 monoclonal antibody.
J&J unveiled new clinical and real-world evidence data in 18 abstracts at ASCO GU 2024. The data highlighted J&J’s dedication to transform the science of genitourinary cancers. Key presentations included new real-world evidence data adding to the strong and differentiated clinical profile of Erleada (apalutamide) in treating various stages of prostate cancer, patient-reported outcomes data from the Phase III MAGNITUDE trial of Akeega (niraparib plus abiraterone acetate) given with prednisone, and an update on the targeted releasing system TAR-200.
The androgen receptor signaling inhibitor Erleada is indicated as a treatment for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and for treating metastatic castration-sensitive prostate cancer (mCSPC). Akeega is a dual-action tablet (DAT) consisting of the highly selective poly (ADP-ribose) polymerase (PARP) inhibitor niraparib and the CYP17 inhibitor abiraterone acetate. Akeega combined with prednisone or prednisolone was cleared for U.S. approval in August 2023 for the treatment of patients with BRCA-mutated mCRPC.
TAR-200 is designed to provide controlled release of gemcitabine (branded as Gemzar) into the bladder, sustaining local drug exposure for weeks at a time. The product candidate’s safety and efficacy are being assessed in Phase II and Phase III trials in patients with muscle-invasive bladder cancer (MIBC) in SunRISe-2 and SunRISe-4 and non-muscle-invasive bladder cancer (NMIBC) in SunRISe-1 and SunRISe-3.
J&J during early February 2024 released positive topline results for nipocalimab from a Phase III pivotal trial in generalized myasthenia gravis (gMG) and a Phase II study in Sjögren’s Disease (SjD). Nipocalimab demonstrated clinical efficacy in gMG and represents the first investigational anti-FcRn to show efficacy in SjD.
LILLY
Lilly made tidal waves in 2023 with the company’s injectable anti-obesity product Mounjaro, which contains the active chemical tirzepatide. Introduced to the U.S. market in 2022, Mounjaro generated worldwide sales of more than $5.16 billion in 2023, including over $2.2 billion in the fourth quarter. Lilly received FDA approval in November of last year for another tirzepatide injectable, branded as Zepbound. Launched in the United States during December, the new medicine generated about $176 million by year-end 2023.
Zepbound is approved as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with obesity (BMI ≥ 30 kg/m2), or overweight (BMI ≥ 27 kg/m2) with at least one weight-related comorbid condition. Zepbound marks the first FDA-approved obesity treatment that activates two incretin hormone receptors, GIP (glucose-dependent insulinotropic polypeptide) and GLP-1, to tackle an underlying cause of excess weight.
Detailed results were unveiled by Lilly in December 2023 from SURMOUNT-4, which demonstrated Zepbound achieved superior mean percent change in body weight versus placebo in adults with obesity or overweight with weight-related comorbidities, excluding type 2 diabetes. The medicine met the primary endpoint of mean percent change in body weight, and all key secondary endpoints for estimands, versus placebo 52 weeks after randomization. People who were randomized to placebo after the lead-in period experienced mean weight regain of 14.8 percent at 88 weeks, indicating use of Zepbound results in sustained weight loss compared to placebo.
Another highly anticipated Lilly medicine to gain U.S. clearance in 2023 was Omvoh (mirikizumab-mrkz). Approved in October, Omvoh infusion (300 mg/15 mL)/injection (100 mg/mL) is the first interleukin-23p19 (IL-23p19) antagonist for the treatment of moderately to severely active UC in adults. Omvoh is the only ulcerative colitis treatment that selectively targets the p19 subunit of IL-23, which plays a role in inflammation related to UC. The product is also Lilly’s first approved treatment for a type of inflammatory bowel disease.
Industry analysts generally view Omvoh as a better therapy than Johnson & Johnson’s Stelara, which is one of the top-selling brands worldwide. Omvoh selectively targets IL-23, whereas Stelara targets IL-12 and IL-23.
Positive results were reported during Q3 2023 in the mirikizumab Phase III VIVID-1 trial, which assessed safety and efficacy for the treatment of adults with moderately to severely active Crohn’s disease. The double-blind, treat-through trial included the investigational interleukin-23p19 antagonist mirikizumab, placebo and active control (ustekinumab) arms. Lilly said this successful late-stage study will from the basis of global regulatory filings for Crohn’s disease.
In addition to Omvoh, industry trackers are excited about the prospects of orforglipron as a daily oral pill for obesity and type 2 diabetes. With a net present value of $13 billion, Evaluate analysts in their 2024 preview report rated orforglipron as the No. 2 most valuable R&D project in the biopharma arena.
Lilly’s first GLP-1 receptor agonist is being evaluated for chronic weight management in participants with obesity or overweight. The company is also studying orforglipron for chronic weight management in the ATTAIN Phase III program and for type 2 diabetes in the ACHIEVE Phase III program.
The Lilly pipeline produced a new oncology medicine that reached the U.S. marketplace in 2023. Jaypirca (pirtobrutinib, 100 mg and 50 mg tablets) won FDA approval on December 1 for a new indication: for adults with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. This is the second U.S. clearance for Jaypirca after the January 2023 Accelerated Approval for treating adult patients with relapsed or refractory MCL after at least two lines of systemic therapy, including a BTK inhibitor.
Jaypirca represents the first FDA-approved non-covalent (reversible) BTK inhibitor. As a highly selective kinase inhibitor, Jaypirca can extend the benefit of targeting the BTK pathway in CLL/SLL patients previously treated with a covalent BTK inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) and a BCL-2 inhibitor. The product uses a novel binding mechanism and has the largest body of evidence of any targeted therapy in patients previously treated with a BTK inhibitor, according to Lilly.
Lilly completed the acquisition of Point Biopharma Global Inc. at the end of 2023. Point Biopharma is a radiopharmaceutical company with a pipeline of clinical and preclinical-stage radioligand therapies in development for treating cancer. Lilly commenced a tender offer to acquire all outstanding shares of Point Biopharma for a purchase price of $12.50 per share in cash (an aggregate of $1.4 billion) payable at closing.
Point Biopharma’s lead programs are in late-stage development. PNT20021 is a prostate-specific membrane antigen (PSMA) targeted radioligand therapy undergoing clinical development for patients with mCRPC after progression on hormonal treatment.
The purchase of Point Biopharma followed the completed acquisitions of Dice Therapeutics Inc., Versanis Bio Inc., Emergence Therapeutics AG, and Sigilon Therapeutics Inc. during the third quarter of 2023. “Lilly executed on business development priorities in the third quarter, including multiple acquisitions that expand our already robust pipeline. We remain focused on growth and delivering new, innovative medicines that make life better for millions of patients around the globe,” stated David A. Ricks, Lilly’s chair and CEO.
MERCK
One of the industry’s most anticipated drug launches of 2024 is Merck’s sotatercept, if the PDUFA date of March 26 results in a successful U.S. approval. Accepted for priority review via a new Biologics License Application (BLA) in September 2023, Merck’s novel investigational activin signaling inhibitor is intended for the treatment of adults with pulmonary arterial hypertension (PAH) (WHO Group 1). If cleared for marketing, sotatercept would represent the first in its class, bringing a novel approach to address a rare and progressive disease of the pulmonary arteries.
Based on a March 2024 U.S. approval, Evaluate analysts have projected sales of $2 billion in 2028 for sotatercept.
Daiichi Sankyo and Merck agreed on a worldwide development and commercialization collaboration in October 2023 for three Daiichi Sankyo DXd ADCs. The collaboration combines Daiichi Sankyo’s proven ADC expertise and DXd technology with Merck’s deep experience in oncology and clinical development capabilities to advance and expand the reach of ADCs for patients across various forms of cancer. Merck was responsible for a $4 billion upfront payment to Daiichi Sankyo in addition to $1.5 billion in continuation payments over a 24-month period, and may make other payments of up to $16.5 billion contingent upon the achievement of future sales milestones, for a total potential consideration of up to $22 billion.
Daiichi Sankyo and Merck will jointly develop and commercialize patritumab deruxtecan, ifinatamab deruxtecan and raludotatug deruxtecan around the globe except for Japan, where Daiichi Sankyo retains exclusive rights. Each of the three potentially first-in-class DXd ADCs are in various stages of clinical development for treating multiple solid tumors both as monotherapy and/or in combination with other treatments.
Patritumab deruxtecan was granted Breakthrough Therapy Designation during December 2021 as a treatment for patients with EGFR-mutated locally advanced or NSCLC with disease progression on or after treatment with a third-generation TKI and platinum-based therapies. Daiichi Sankyo and Merck received and announced the FDA’s acceptance of the product’s BLA on December 22, 2023. The PDUFA date is scheduled for June 26, 2024.
Ifinatamab deruxtecan is being developed as monotherapy in IDeate-01 (ClinicalTrials.gov; NCT05280470), a Phase II study in patients with previously treated extensive-stage small cell lung cancer (SCLC). Updated results from a subgroup analysis of a Phase I/II study of ifinatamab deruxtecan in SCLC were presented at the IASLC 2023 World Conference on Lung Cancer.
Raludotatug deruxtecan is being investigated in a first-in-human Phase I study.
Merck completed the acquisition of Prometheus Biosciences Inc. in June 2023 for $200.00 per share in cash for a total equity value of $10.8 billion. The acquisition delivers industry-leading research capability, and bolsters Merck’s pipeline with a novel candidate for ulcerative colitis, Crohn’s disease and other autoimmune conditions. MK-7240 (formerly PRA-023) is a humanized monoclonal antibody (mAb) directed to tumor necrosis factor (TNF)-like ligand 1A (TL1A), a target associated with intestinal inflammation and fibrosis. MK-7240 is being developed for treating immune-mediated diseases, including UC, Crohn’s disease (CD) and other autoimmune conditions.
Merck landed a deal to acquire Harpoon Therapeutics Inc. in January 2024. Through a subsidiary, Merck will acquire Harpoon for $23.00 per share in cash for a total equity value of $680 million. The transaction includes HPN328, an investigational delta-like ligand 3 (DLL3) targeting T-cell engager being studied in certain patients with small cell lung cancer and neuroendocrine tumors.
The lead candidate in Harpoon’s arsenal, HPN328 is an inhibitory canonical Notch ligand that is expressed at high levels in SCLC and neuroendocrine tumors. HPN328 is undergoing a Phase I/II study (NCT04471727) exploring the safety, tolerability and pharmacokinetics of HPN328 monotherapy in patients with advanced cancers associated with expression of DLL3. The clinical trial is also investigating HPN328 in combination with atezolizumab in patients with SCLC.
Merck entered into a definitive pact through a subsidiary to acquire Caraway Therapeutics Inc. for a total potential consideration of up to $610 million, including an undisclosed upfront payment as well as contingent milestone payments. The upfront payment was expensed by Merck during fourth-quarter 2023 and included in non-GAAP results. The acquisition underscores Merck’s continuing dedication to develop treatments for neurodegenerative diseases.
Caraway is a preclinical biopharma company that has been pursuing innovative approaches for treating genetically defined neurodegenerative and rare diseases. Caraway has built a pipeline of novel, small-molecule therapeutics for treating genetically defined neurodegenerative and rare diseases.
U.S. regulators gave the green light to Merck’s Welireg in December 2023 as the first hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor approved for adults with advanced renal cell carcinoma (RCC) following a PD-1 or PD-L1 inhibitor and a VEGF-TKI. The marketing clearance of Welireg represents the first time a new treatment has been approved in a novel therapeutic class in advanced RCC since 2015.
Merck continues to evolve the vast roladex of approved uses and continued development of Keytruda (pembrolizumab), the world’s top-selling medicine. An anti-programmed death receptor-1 (PD-1) therapy, Keytruda works by increasing the ability of the body’s immune system to help detect and fight tumor cells. The humanized monoclonal antibody blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes that may affect tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program, including more than 1,600 studies investigating Keytruda across a wide range of cancers and treatment settings. Keytruda’s clinical program seeks to understand the role of the medicine across cancers and the factors that may predict a patient’s likelihood of benefiting from treatment with the product, including exploring several different biomarkers.
Keytruda, in combination with chemoradiotherapy (CRT), won FDA approval in January 2024 for the treatment of patients with FIGO (International Federation of Gynecology and Obstetrics) 2014 Stage III-IVA cervical cancer. Keytruda represents the first anti-PD-1 therapy cleared for marketing in combination with chemoradiotherapy for these patients. The U.S. clearance marks the third FDA-approved indication for Keytruda in cervical cancer and the 39th indication for the blockbuster medicine in the United States.
Keytruda won FDA clearance in December 2023 in combination with Padcev (enfortumab vedotin-ejfv), an antibody-drug conjugate, for adults with locally advanced or metastatic urothelial cancer. The U.S. approval occurred nearly five months ahead of the PDUFA goal date of May 9, 2024.
Keytruda received FDA approval in combination with fluoropyrimidine- and platinum-containing chemotherapy during November 2023 for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or GEJ adenocarcinoma. The marketing clearance represents the seventh gastrointestinal cancer indication for Keytruda-based regimens in the United States.
Two weeks before that FDA approval, the U.S. regulatory agency cleared for marketing the anti-PD-1 therapy in combination with gemcitabine and cisplatin, for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer (BTC).
Teammates Merck and Moderna Inc. announced in December the start of INTerpath-002. The pivotal Phase III randomized study is assessing V940/mRNA-4157, an investigational individualized neoantigen therapy (INT), in combination with Keytruda as adjuvant treatment in patients with completely resected Stage II, IIIA or IIIB (with nodal involvement [N2]) NSCLC.
In addition to INTerpath-002, the combination of V940 and Keytruda is being studied in INTerpath-001, formerly referred to as V940-001 (NCT05933577). The global, randomized, double-blind, placebo- and active-comparator-controlled Phase III trial is testing 1,089 patients with resected high-risk (Stage IIB-IV) melanoma. Moderna and Merck intend to continue expansion of the comprehensive clinical development program for V940 to additional tumor types.
Merck’s investigational 21-valent pneumococcal conjugate vaccine V116 was accepted for priority review via a new BLA in December 202. U.S. regulators set a PDUFA date of June 17, 2024.
Merck announced Phase III study initiations for four investigational candidates from the Rahway, N.J.-based company’s promising hematology and oncology pipeline in early January. Worldwide Phase III trials were launched for bomedemstat (LSD1 inhibitor), nemtabrutinib (BTK inhibitor), MK-2870 (anti-TROP2 ADC) and MK-5684 (CYP11A1 inhibitor).
The orally available lysine-specific demethylase 1 (LSD1) inhibitor bomedemstat is being investigated for the treatment of certain patients with essential thrombocythemia (ET). The investigational oral, reversible, non-covalent BTK inhibitor emtabrutinib is being assessed as a treatment for certain patients with CLL and small lymphocytic lymphoma SLL. The investigational trophoblast cell-surface antigen 2 (TROP2)-directed ADC MK-2870 is being studied in collaboration with Kelun-Biotech Pharmaceutical Co. for certain patients with NSCLC and certain patients with previously treated endometrial carcinoma. The CYP11A1 inhibitor MK-5684 is being studied in collaboration with Orion Corp. as a treatment for certain patients with metastatic castration-resistant prostate cancer (mCRPC).
Novo Nordisk
Novo Nordisk has altered the weight-loss and diabetes marketplace with the game-changing medicines Wegovy and Ozempic. “Novo Nordisk sells Ozempic, a type 2 diabetes medicine, under other brand names: Rybelsus, and in obesity Wegovy. All contain the same active ingredient, semaglutide, a GLP-1 agonist that is forecast to generate more than $28 billion in annual sales across all its brands next year,” according to the Evaluate Preview 2024 report.
On the horizon is another potential market-altering performer in the diabetes and obesity category, CagriSema. The fixed-dose combination of the amylin analog cagrilintide and GLP-1 analog semaglutide for type 2 diabetes and obesity is on tap for a pivotal program readout from 2025.
With a new present value of $30.2 billion, CagriSema was rated No. 1 by Evaluate as biopharma’s most valuable R&D project. Novo Nordisk launched a new Phase III study comparing CagriSema against Lilly’s Zepbound in people with obesity.
Novo Nordisk shared in January the first Phase IIIa results for once-weekly IcoSema, a fixed-ratio combination of basal insulin icodec and semaglutide. The COMBINE 3 study was successfully completed and achieved the primary endpoint with IcoSema showing non-inferior reduction in HbA1c versus daily basal-bolus treatment (insulin glargine U100 and insulin aspart) in people with type 2 diabetes. IcoSema was superior versus insulin glargine U100 and insulin aspart in estimated rates of severe or clinically significant (blood glucose below 3.0 mmol/L) hypoglycemia.
Novo Nordisk stopped the kidney outcomes trial FLOW (effect of semaglutide versus placebo on the progression of renal impairment in people with type 2 diabetes and chronic kidney disease) in October 2023. The decision to stop the study is based on a recommendation from the independent Data Monitoring Committee concluding that the results from an interim analysis met certain pre-specified criteria for ending the clinical trial early for efficacy.
Novo Nordisk completed the acquisition of Inversago Pharma in September 2023 to develop new therapies for individuals living with obesity, diabetes, and other serious metabolic diseases. Inversago was a private, Montreal-based developer of CB1 receptor-based therapies for the potential treatment of obesity, diabetes and complications associated with metabolic disorders. Novo Nordisk agreed to acquire Inversago for up to $1.075 billion in cash if certain development and commercial milestones were achieved.
Inversago’s lead development asset, the oral CB1 inverse agonist INV-202, is designed to preferentially block the receptor protein CB1 in peripheral tissues including adipose tissues, the gastro-intestinal tract, the kidneys, liver, pancreas, muscles and lungs. CB1 plays a significant role in metabolism and appetite regulation.
Novo Nordisk and Valo Health Inc. reached a deal in September 2023 to discover and develop novel treatments for cardiometabolic diseases based on Valo’s large human dataset and computation powered by artificial intelligence. The collaboration will apply Valo’s Opal Computational Platform and real-world patient dataset to allow for the discovery and development of novel cardiometabolic drug programs.
Novo Nordisk is licensing three preclinical drug discovery programs in cardiovascular diseases discovered and developed by Valo using the platform. Valo agreed to receive an upfront payment and a potential near-term milestone payment, amounting to $60 million. Valo is eligible to receive milestone payments for up to 11 programs, up to $2.7 billion, plus research and development funding and potential royalty payments.
Novo Nordisk agreed to acquire ocedurenone for uncontrolled hypertension with potential application in cardiovascular and kidney disease from KBP Biosciences PTE. Ltd. for up to $1.3 billion in October 2023. The orally administered, small molecule, non-steroidal mineralocorticoid receptor antagonist is undergoing the Phase III study CLARION-CKD in patients with uncontrolled hypertension and advanced CKD.
“This deal is closely aligned with our strategic focus on expanding from our core in diabetes into other serious chronic diseases, including through novel drug modalities, to help many more patients living with unmet medical needs,” noted Camilla Sylvest, executive VP, commercial strategy and corporate affairs at Novo Nordisk.
At the beginning of 2024, Novo Nordisk entered into separate research collaborations with Omega Therapeutics Inc. and Cellarity Inc. on novel treatment approaches for cardiometabolic diseases. These mark the first two programs inked via the framework collaboration between Flagship Pioneering and Novo Nordisk to leverage Flagship’s bioplatform companies to develop novel treatment approaches for cardiometabolic diseases. Novo Nordisk will reimburse research and development costs and each company, and Flagship’s Pioneering Medicines were eligible to receive up to $532 million in upfront and milestone payments, in addition to tiered royalties.
The Omega program will leverage its proprietary platform technology to develop an epigenomic controller designed to enhance metabolic activity as a part of a potential new treatment approach for managing obesity. The Cellarity collaboration intends to unravel novel biological drivers of metabolic dysfunction-associated steatohepatitis and will leverage the company’s platform to develop a small molecule therapy against this disease.
As this magazine edition was going to press, Novo Nordisk announced on February 5 a deal to acquire three fill-finish sites from Novo Holdings A/S in connection with a transaction where Novo Holdings agreed to acquire the global contract development and manufacturing organization Catalent Inc. Novo Nordisk and Catalent have a long-standing collaboration, and Novo Nordisk will acquire the three manufacturing sites for an upfront payment of $11 billion.
PFIZER
Pfizer is undergoing a transition as sales for the company’s COVID-19 vaccine Comirnaty and oral antiviral treatment Paxlovid (nirmatrelvir tablets; ritonavir tablets) continue to decline since their boom period. “Declining demand across Pfizer’s pandemic portfolio will rob the developer of its revenue advantage over its big pharma peers next year, as well as its position as the sector’s largest maker of prescription drugs,” Evaluate analysts say.
With many billions of revenue generated by those products, Pfizer has turned back to what helped make the company an industry leader throughout the 2000s: big-time M&A deals. According to Pfizer’s Q4 2023 results announcement, last year set the stage for the company’s future growth potential: the completed Seagen acquisition, creating a world-class oncology organization; the launch of a significant amount of new products and indications; and a realigned commercial organization to improve focus, speed, and execution.
Pfizer Chairman and CEO Dr. Albert Bourla said, “We are encouraged by the strong performance of our non-Covid products in the fourth quarter of 2023, including significant contributions from new launches and robust year-over-year growth for several key in-line brands. In 2023, Pfizer received a record number of nine new molecular entity approvals by the U.S. Food and Drug Administration – medicines and vaccines that are expected to favorably impact Pfizer’s performance in the coming years.”
Dr. Bourla continued, “In addition, we completed the acquisition of Seagen in December 2023, a critical step toward our goal to achieve world-class Oncology leadership. With the combined strength of Pfizer’s and Seagen’s talent, portfolios and platforms, we believe we have the potential to transform outcomes by delivering cancer medicines that help patients live better and longer lives.”
He added, “We are entering 2024 with a solid foundation. We believe our commitment to execution, maximizing the performance of our new products, and delivering the next wave of pipeline innovation will fuel Pfizer’s growth and make a difference in the lives of patients everywhere.”
According to Fierce Pharma analysis, “The Pfizer-Seagen merger is the largest M&A deal in biopharma since AbbVie acquired Allergan for $63 billion in June of 2019. It will give Pfizer four approved products and a deep pipeline of antibody-drug conjugate candidates. Pfizer said it expects the products brought by Seagen to bring $10 billion in additional annual revenues by 2030.”
Pfizer announced changes during December in the company’s commercial organization to incorporate Seagen, effective January 1, 2024. Seagen comes to Pfizer following four acquisitions in 2022 expected to significantly strengthen Pfizer’s pipeline: Arena Pharmaceuticals Inc., Biohaven Pharmaceuticals Inc., Global Blood Therapeutics Inc., and ReViral Ltd.
With the addition of Seagen’s four approved medicines – Padcev, Adcetris (brentuximab vedotin), Tivdak (tisotumab vedotin), and Tukysa (tucatinib) – Pfizer’s industry-leading Oncology portfolio includes more than 25 approved medicines and biosimilars across more than 40 indications, including nine prescription products that are blockbuster or have the potential to be blockbuster.
Mentioned earlier in this article, FDA approval was granted during December 2023 for a combination of Padcev with the world’s No. 1-selling medicine Keytruda from Merck for treating adults with la/mUC based on the results from the Phase III EV-302 study. This drug combination represents the first such one approved to offer an alternative to platinum-containing chemo, the current standard of care in first-line la/mUC.
The U.S. drug regulator accepted the sBLA for Tivdak in January 2024 seeking to convert the accelerated approval of the ADC product to full approval, for treating patients with recurrent or metastatic cervical cancer with disease progression on or after first-line therapy. The sBLA is supported by efficacy and safety data from the worldwide, randomized, Phase III innovaTV 301 study. The marketing application was given Priority Review with a PDUFA goal date of May 9, 2024.
Xtandi (enzalutamide) was granted U.S. approval in November 2023 via an sNDA following FDA expedited development and review programs (Priority Review designation, Fast Track designation, Real-time Oncology Review). The marketing clearance is based on results from the Phase III EMBARK study. Xtandi is the first androgen receptor signaling inhibitor FDA-approved for treating patients with nonmetastatic castration-sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR).
On the clinical development front for NMEs, Pfizer’s BLA was accepted during December 2023 for the anti-tissue factor pathway inhibitor (anti-TFPI) candidate marstacimab for individuals living with hemophilia A or hemophilia B without inhibitors to Factor VIII (FVIII) or Factor IX (FIX). The U.S. regulatory agency set a PDUFA action date during fourth-quarter 2024.
Pfizer presented results during December from the pivotal Phase III BASIS study assessing marstacimab as a treatment for people with severe hemophilia A and moderately severe to severe hemophilia B without inhibitors to FVIII or FIX. Data from the BASIS study presented at ASH 2023 showed a statistically significant and clinically meaningful effect on annualized bleeding rate. The safety profile for marstacimab was consistent with Phase I/II results.
Pfizer and Valneva SE reported in December the completed recruitment for the Phase III VALOR study exploring VLA15, an investigational multivalent protein subunit vaccine for Lyme disease. The study builds on previous positive Phase I and II trial results and includes adult and pediatric participants, with the aim to confirm the efficacy, safety, lot consistency, and immunogenicity of VLA15. The VALOR study is anticipated to be concluded by year-end 2025.
Pfizer reported topline results in December from the Phase IIb study investigating the oral glucagon-like peptide-1 receptor agonist (GLP-1RA) candidate danuglipron in adults with obesity and without type 2 diabetes. The clinical trial met the primary endpoint showing statistically significant change in body weight from baseline. Pfizer says future development of danuglipron will be concentrated on a once-daily formulation, with pharmacokinetic data expected during first-half 2024, which will help to inform a potential path forward.
In another December pipeline update, Arvinas Inc. and Pfizer presented interim results from the Phase Ib study investigating vepdegestrant (ARV-471), a novel oral PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader, in combination with palbociclib (marketed as Ibrance). Data from the combination cohort showed encouraging clinical activity in heavily pre-treated patients with a median of four lines of therapy across disease settings with locally advanced or metastatic ER positive/human epidermal growth factor 2 (HER2) negative (ER+/HER2-) breast cancer.
ROCHE
“Roche’s new chief executive continued to make good on his pledge to restock the group’s pipeline, buying obesity play Carmot for $2.7 billion up front, weeks after splashing out $7.1 billion on Roivant’s inflammatory bowel disease asset,” according to the Evaluate 2024 Preview report. Roche entered into a definitive merger deal in December 2023 to acquire Carmot Therapeutics Inc., including three clinical-stage assets with best-in-class potential in obesity and diabetes. Roche will pay an upfront purchase price of $2.7 billion and additional milestone payments of up to $400 million. According to management, Carmot’s research and development portfolio of clinical-stage incretins has great potential to treat obesity, diabetes, and potentially other diseases both as standalone medicines and in combination with Roche’s in-house assets.
The acquisition provides Roche with access to a differentiated portfolio of incretins including the lead asset CT-388, a Phase II-ready, dual GLP-1/GIP receptor agonist for treating obesity in patients with and without type 2 diabetes. Injected subcutaneously once weekly, CT-388 has potential as a standalone and combination therapy to improve weight loss and to be expanded to other indications.
The existing clinical data for Carmot’s assets, particularly CT-388, suggests a best-in-class potential to achieve and maintain weight loss with differentiated efficacy. The assets provide an opportunity for combinations with existing Roche pipeline assets including ones concentrated on other benefits, including preserving muscle mass. Incretins are gut hormones secreted after food intake that play a role in modulating blood glucose by stimulating insulin secretion and suppressing appetite. The incretin-based portfolio could additionally be expanded to other indications where incretins play a role such as cardiovascular, retinal and neurodegenerative disease.
Roche agreed to acquire Telavant Holdings Inc., owned by Roivant Sciences Ltd. and Pfizer, during October 2023. Roche is responsible for an upfront purchase price of $7.1 billion and a near-term milestone payment of $150 million. Telavant was jointly formed by Roivant and Pfizer during 2022 to develop and commercialize the novel TL1A directed antibody RVT-3101 in the United States and Japan.
The transaction includes the development, manufacturing, and commercialization rights in those two countries for RVT-3101. The promising new therapy is undergoing clinical development for people suffering from inflammatory bowel disease, including ulcerative colitis and Crohn’s disease. The Phase III-ready antibody represents first-in-class and best-in-disease potential, a novel mode of action, and strong Phase IIb data in ulcerative colitis. Given the antibody’s novel mode of action targeting inflammation and fibrosis, RVT-3101 has the potential to be applied in multiple other diseases.
RVT-3101 targets inflammatory and fibrotic pathways by inhibiting TL1A. RVT-3101 has been demonstrated to modulate the severity of inflammation and fibrosis by stimulating the TH1 and TH17 pathways, in addition to activating fibroblasts. As such, RVT-3101 has the potential to allow for greater efficacy by hitting multiple inflammatory and fibrotic pathways.
“The recent Phase IIb for RVT-3101 delivered the first long-term, robust dataset demonstrating improved clinical remission in the maintenance treatment phase,” said Levi Garraway, Roche’s chief medical officer and head of global product development.“Given this promising data, we believe that RVT-3101 has the potential to be the first therapy that offers both high efficacy and safety for people with inflammatory bowel disease and the convenience of an at-home, subcutaneous administration.” As part of the deal, Roche additionally received an option to enter into a worldwide collaboration with Pfizer on a next-generation p40/TL1A directed bispecific antibody, undergoing Phase I development.
The Evaluate 2024 Preview report includes two Roche assets on its “Biopharma’s valuable R&D projects” listing. The anti-tigit mab tiragolumab for lung and other cancers has a net present value of $5.2 billion per the report (which ranks fourth-highest on the list), with pivotal readouts due from first-quarter 2024. The oral SERD giredestrant from Roche for breast cancer has an NPV of $3.8 billion (ranked No. 7), with a pivotal program due to yield data during 2025.
New clinical data for Roche’s CD20xCD3 T-cell engaging bispecific antibody program including Columvi and Lunsumio presented at ASH 2023 support continued benefit for people with lymphoma, according to the company. Based on 32-month and three-year follow-ups of two pivotal studies for fixed-duration treatments of Columvi (glofitamab) and Lunsumio (mosunetuzumab), data demonstrate that remissions were maintained in the majority of patients with heavily pre-treated lymphomas. Also, new early-phase data of novel Columvi or Lunsumio combination regimens support ongoing investigation in Phase III trials in earlier lines of DLBCL and FL.
“Updated data from pivotal studies of Columvi and Lunsumio continue to provide compelling evidence for how fixed-duration therapies can deliver sustained, long-term benefit for people with difficult-to-treat lymphomas,” Garraway commented. “Our data at ASH also demonstrate progress in evaluating our bispecific antibodies in earlier stages of disease and additional types of lymphoma so more people can benefit from our therapies.”
The CD20xCD3 T-cell engaging bispecific antibody Columvi is designed to target CD3 on the surface of T-cells and CD20 on the surface of B-cells. The first-in-class CD20xCD3 T-cell engaging bispecific antibody Lunsumio is designed to target CD3 on the surface of T-cells and CD20 on the surface of B-cells.
Positive Phase III results for an inavolisib drug combination in people with advanced hormone receptor-positive, HER2-negative breast cancer with a PIK3CA mutation were announced by Roche in December. The Phase III INAVO120 trial is studying the investigational therapy inavolisib, in combination with palbociclib (marketed as Ibrance) and fulvestrant as a potential first-line treatment option for people with PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative, endocrine-resistant, locally advanced or metastatic breast cancer. The clinical trial met the primary endpoint of PFS, showing a statistically significant and clinically meaningful improvement versus palbociclib and fulvestrant alone.
The oral targeted treatment inavolisib has best-in-class potential that could provide well-tolerated, durable disease control and potentially improved outcomes for people with hormone receptor (HR)-positive, PIK3CA-mutated breast cancer. Inavolisib is being evaluated in three Roche-sponsored Phase III trials in PIK3CA-mutated locally advanced or metastatic breast cancer.
Roche reported in December that the primary analysis of the Phase III HAVEN 7 trial reinforced the efficacy and safety of Hemlibra (emicizumab) in previously untreated or minimally treated infants with severe hemophilia A without factor VIII inhibitors. At nearly two years median follow-up in the descriptive, single-arm study, no babies experienced spontaneous bleeds requiring treatment, and every treated bleed was as a result of trauma. A bispecific factor IXa- and factor X-directed antibody, Hemlibra is designed to bring together factor IXa and factor X – proteins involved in the natural coagulation cascade – and restore the blood-clotting process for people with hemophilia A.
Vabysmo (faricimab) was given the FDA green light in October 2023 for the treatment of macular edema following retinal vein occlusion. RVO marks the third approved indication for Vabysmo, in addition to neovascular or “wet” age-related macular degeneration and diabetic macular edema. Together, the three retinal conditions affect about 70 million people and are among the leading causes of vision loss. The approval is based on two Phase III trials showing early and sustained vision improvements that were non-inferior to aflibercept. Vabysmo additionally demonstrated rapid and robust drying of retinal fluid.
The blockbuster brand Xolair (omalizumab) was granted U.S. priority review in December 2023 for children and adults with food allergies based on positive National Institutes of Health Phase III trial results. If the sBLA is approved, Xolair would represent the first medicine to reduce allergic reactions to multiple foods following an accidental exposure. Interim analysis results from the first-of-its-kind Phase III OUtMATCH trial demonstrated Xolair significantly increased the amount of peanut, milk, egg and cashew it took to cause an allergic reaction.
Xolair is the only approved antibody designed to target and block immunoglobulin E (IgE). By reducing free IgE, down-regulating high-affinity IgE receptors and limiting mast cell degranulation, Xolair minimizes the release of mediators throughout the allergic inflammatory cascade.
SANOFI
Sanofi’s pipeline is undergoing a transformation to accelerate growth fueled by a record amount of potential blockbuster launches, “paving the way to industry leadership in immunology,” according to the company. Management unveiled during December 2023 an update on Sanofi’s strong pipeline, including a company-record 12 blockbuster opportunities under clinical assessment: nine innovative medicines and vaccines with €2 to €5 billion in peak sales potential, and three “pipeline-in-a-product” assets with a potential of more than €5 billion peak sales.
Recently launched and future pharmaceutical assets are projected to account for more than €10 billion of annual sales by 2030, driven by late-stage pipeline assets including amlitelimab, frexalimab, itepekimab and tolebrutinib, as well as recently launched medicines such as Altuviiio ([antihemophilic factor (recombinant)), Sarclisa (isatuximab) and Tzield (teplizumab-mzwv).
Sanofi said enhanced research and development concentration aims to deliver a 50 percent increase in Phase III studies in 2024 and 2025, creating the greatest pipeline momentum in the company’s history. Sanofi’s R&D dedication will support an expected 25 mid-stage to late-stage read-outs and up to 19 regulatory filings for the company’s pharma assets in the next two years.
Management’s ambition for Sanofi to become an immunology powerhouse will be driven by recent and future launched pharmaceutical assets, in addition to the strong growth of the megabrand Dupixent (dupilumab) and the Vaccines business. The Q3 2023 U.S. launch of Beyfortus (nirsevimab-alip) is expected to help drive growth for the Vaccines business.
According to Sanofi, “Focusing on its unprecedented portfolio of 12 new molecular entities with blockbuster potential, including multiple late-stage assets, the company will be prioritizing development and leveraging its leadership in immunology across all other therapeutic areas. Sanofi will also share its ambitions to break efficacy ceilings and expand into new indications, generating a steady flow of predominantly wholly owned new assets.”
Sanofi’s pipeline of 12 potential blockbuster assets in immunology and vaccines includes the three “pipeline-in-a-product” assets: amlitelimab, frexalimab, and SAR441566 (Oral TNFR1si), each with peak sales potential of more than €5 billion. Others include treatments for multiple sclerosis (tolebrutinib), asthma (lunsekimig, rilzabrutinib), inflammatory bowel disease (Anti-TL1A), atopic dermatitis (IRAK4 degrader), and COPD (itepekimab). Additional potential blockbusters consist of vaccines to combat acne, extraintestinal pathogenic E. coli, and RSV in older adults.
The blockbuster brand Dupixent is anticipated to continue the drug’s strong performance and generate a low double-digit net sales growth CAGR from 2023 to 2030, supported by expected new indications such as chronic obstructive pulmonary disease (COPD) and greater penetration in approved indications. On January 25, 2024, Dupixent became the first FDA-approved treatment for children aged 1 year and older with eosinophilic esophagitis (EoE). The expanded indication marks the second disease for which Dupixent is approved in children this young, underscoring Sanofi’s dedication to bringing therapies to young patients with significant unmet needs.
Also in January, the product’s U.S. label was updated with data further supporting use in atopic dermatitis with moderate-to-severe hand and foot involvement. The data included the first Phase III study specifically assessing a biologic in this difficult-to-treat population.
Dupilumab is being jointly developed by Regeneron Pharmaceuticals Inc. and Sanofi through a worldwide collaboration agreement. As of January, dupilumab had been assessed across more than 60 clinical studies involving over 10,000 patients with various chronic diseases driven in part by type 2 inflammation. Regeneron and Sanofi are evaluating dupilumab in a broad range of diseases driven by type 2 inflammation or other allergic processes in Phase III.
According to Phase III data released in December, Sarclisa plus KRd significantly improved rate of minimal residual disease negativity in transplant-eligible patients with newly diagnosed multiple myeloma compared to KRd alone. Additionally, another Phase III study for the monoclonal antibody met the primary endpoint of progression free survival in patients with newly diagnosed multiple myeloma not eligible for transplant.
The pipeline received a potential best-in-class rare disease asset for Alpha-1 Antitrypsin Deficiency (AATD) when Sanofi announced in January the acquisition of Inhibrx Inc. The human recombinant protein INBRX-101 holds the promise of enabling AATD patients to achieve normalization of serum AAT levels with less frequent (monthly versus weekly) dosing. The acquisition supports Sanofi’s portfolio growth strategy and complements the company’s 30-year heritage in rare diseases and proven industry leadership in immunology and inflammation.
VERTEX
Vertex Pharmaceuticals Inc. kicked off 2024 with various clinical updates. “2023 was marked by continued strong performance in the cystic fibrosis business and acceleration of our development stage pipeline, propelling the company into 2024 with tremendous momentum,” stated President and CEO Reshma Kewalramani, M.D. “We continue to reach more patients than ever before with our CF medicines; we’ve launched Casgevy in the U.S., UK, and Bahrain following the historic approvals of this gene editing therapy late last year, and we are well positioned to advance our mission of bringing additional transformative medicines to people with serious diseases.”
Casgevy represents the first-ever approval of a CRISPR-based gene-editing therapy in the United States, with FDA marketing clearance occurring during December 2023 for treating sickle cell disease. Casgevy (exagamglogene autotemcel [exa-cel]), a CRISPR/Cas9 genome-edited cell therapy, won FDA approval for the treatment of sickle cell disease (SCD) in patients 12 years and older with recurrent vaso-occlusive crises (VOCs). Vertex leads worldwide development, manufacturing and commercialization of Casgevy with support from CRISPR Therapeutics.
The momentum grew stronger for the CRISPR/Cas9 gene-edited cell therapy in January 2024 with FDA approval ahead of the PDUFA date for a new indication: the treatment of transfusion-dependent beta thalassemia (TDT) in patients 12 years and older. In other Casgevy news, Vertex completed enrollment in two global Phase III trials in patients 5 to 11 years of age with SCD or TDT.
Clarivate identified 13 potential blockbuster drugs and game changers in the company’s annual drugs to watch report for 2024, including Casgevy. “All eyes are on exagamglogene autotemcel (exa-cel) and lovotibeglogene autotemcel, which are set become the first disease-modifying therapies for sickle cell disease and beta-thalassemia, a significant achievement for a patient population with debilitating, life-altering diseases that have limited symptomatic and curative treatments currently available. The excitement around exagamglogene autotemcel also stems from the landmark first approval of a CRISPR/Cas9 gene-edited therapy globally, and the approval sets the stage for upcoming approvals in other regions,” according to Clarivate analysis. Lyfgenia (lovotibeglogene autotemcel) is developed by bluebird bio Inc.
On the cystic fibrosis front, Vertex is developing a next-in-class triple combo. The company has completed three pivotal trials assessing the CFTR modulator therapy vanzacaftor/tezacaftor/deutivacaftor (the “vanza triple”) compared to Vertex’s Trikafta (elexacaftor/tezacaftor/ivacaftor and ivacaftor) in patients with CF ages 6 years of age and older (ages 12+ in SKYLINE 102 and 103 studies; ages 6-11 in the RIDGELINE study).
Vertex reported positive results during February 2024 for the vanza triple combination, the most comprehensive Phase III pivotal program ever performed by the company for treating cystic fibrosis. Treatment with the once-daily vanza triple CFTR modulator regimen met all primary and key secondary endpoints in two randomized controlled studies in people with cystic fibrosis ages 12 years and older. Results were more pronounced in the single-arm study in children ages 6 to 11 years, according to Vertex.
In other recent news on the cystic fibrosis front, dosing was completed in the single ascending dose portion of the Phase I/II clinical trial of VX-522 and Vertex initiated the multiple ascending dose portion of the study. The CFTR mRNA therapeutic is being developed by Vertex in collaboration with Moderna for the >5,000 patients with cystic fibrosis who do not make any CFTR protein and cannot benefit from CFTR modulators.
Vertex is developing various assets in the pain-management segment, including VX-548. The new drug candidate has completed three Phase III trials for treating moderate-to-severe acute pain, including two randomized placebo-controlled studies: one following abdominoplasty and one following bunionectomy surgery, and a third single-arm safety and effectiveness trial, which enrolled surgical and non-surgical patients with moderate-to-severe acute pain.
Vertex shared results from all three of the late-stage studies for VX-548 on January 30, 2024. Treatment with the selective NaV1.8 inhibitor resulted in statistically significant improvement in pain versus placebo as well as a clinically meaningful reduction in pain from baseline in the abdominoplasty and bunionectomy randomized controlled studies. VX-548 treatment was additionally demonstrated to be effective in the single-arm study in a wide range of surgical and non-surgical pain conditions for up to 14 days. VX-548 was found to be safe and well tolerated in all three clinical trials. The company intends to file a New Drug Application with FDA regulators by mid-2024.
Vertex expects to begin a Phase II trial with an oral form of the next-generation NaV1.8 inhibitor VX-993 for treating moderate-to-severe acute pain in 2024.
In other VX-548 news, following the December 2023 release of positive Phase II data with the selective NaV1.8 inhibitor in diabetic peripheral neuropathy (PNP) – which represents ~20 percent of peripheral neuropathic pain patients – the company intended to meet with regulators during first-quarter 2024 and expected to advance VX-548 into pivotal development.
Additionally, Vertex initiated a Phase II trial of VX-548 in lumbosacral radiculopathy, another type of peripheral neuropathic pain and the largest patient segment (more than 40 percent) within the PNP category.
Vertex anticipates beginning a Phase II study with an oral form of VX-993 for treating PNP in 2024.
Vertex is developing the clinical asset inaxaplin (VX-147) for APOL1-Mediated Kidney Disease (AMKD). The company completed enrollment in the Phase IIB dose-ranging portion of the trial of inaxaplin for the treatment of patients with AMKD. Vertex planned to start Phase III during the first quarter of 2024.
The Boston-based company is developing an allogeneic, stem cell-derived, fully differentiated, insulin-producing islet cell therapy. Vertex has completed enrollment in Parts A, B, and C of the Phase I/II trial of VX-880, which is used in conjunction with standard immunosuppression, in patients with T1D and impaired awareness of hypoglycemia and recurrent hypoglycemic events.
The clinical study for VX-264, which encapsulates the same VX-880 cells in a device that is designed to eliminate the need for immunosuppressants, is in a multi-part Phase I/II trial.
