FDA Grants Priority Review to Merck’s Application for KEYTRUDA Plus Padcev for the First-Line Treatment of Patients With Locally Advanced or Metastatic Urothelial Cancer
Merck, operating as MSD internationally, reported that the U.S. Food and Drug Administration (FDA) has prioritized the review of a supplementary Biologics License Application (sBLA). This application focuses on obtaining approval for KEYTRUDA, Merck’s anti-PD-1 therapy, in conjunction with Padcev (enfortumab vedotin-ejfv), an antibody-drug conjugate. The intended use is for treating adult patients dealing with locally advanced or metastatic urothelial carcinoma (la/mUC). The FDA is expediting the review through its Real-Time Oncology Review (RTOR) initiative, aiming to enhance the efficiency of the evaluation process and ensure the timely availability of treatments. The FDA has outlined a target action date, or Prescription Drug User Fee Act (PDUFA), set for May 9, 2024.
The supplemental Biologics License Application (sBLA) draws its foundation from data obtained in the Phase III KEYNOTE-A39 trial, also recognized as EV-302. In collaboration with Seagen and Astellas, this research showcased that the combination of KEYTRUDA and enfortumab vedotin resulted in a statistically significant and clinically meaningful enhancement in both overall survival (OS) and progression-free survival (PFS) when compared to traditional chemotherapy (gemcitabine plus cisplatin or carboplatin). These findings unveiled as late-breaking data during a Presidential Symposium session at the European Society for Medical Oncology Congress 2023, revealed a 53% reduction in the risk of death with KEYTRUDA plus enfortumab vedotin, leading to a median OS of 31.5 months as opposed to 16.1 months with chemotherapy (improvement exceeding 15 months; HR=0.47 [95% CI, 0.38-0.58]; p<0.00001).
The FDA's acknowledgment of this application for priority review, along with inclusion in the RTOR program, highlights the critical need to make this treatment option available to a broader spectrum of patients grappling with locally advanced or metastatic urothelial carcinoma," commented Dr. Eliav Barr, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer at Merck Research Laboratories. "Our commitment is to collaborate closely with the FDA to swiftly offer this significant option to patients.
Merck, in partnership with Seagen and Astellas, is exploring this combination through an extensive clinical development initiative across various stages of urothelial cancer. This includes ongoing Phase III clinical trials in muscle-invasive bladder cancer, namely KEYNOTE-B15 and KEYNOTE-905.
Roche Enters Into A Definitive Merger Agreement to Acquire Carmot Therapeutics, Including Three Clinical Stage Assets With Best-In-Class Potential in Obesity And Diabetes
Roche declared a definitive merger agreement to purchase Carmot Therapeutics, Inc., a privately held American company situated in Berkeley, California. Carmot's research and development portfolio encompasses clinical-stage subcutaneous and oral incretins, exhibiting best-in-class potential for treating obesity in patients both with and without diabetes, along with several preclinical programs.
Roche's latest acquisition opens doors to a unique lineup of incretins, notably featuring:
CT-388, the primary asset, is a Phase-II ready, dual GLP-1/GIP receptor agonist designed for treating obesity in both type 2 diabetes and non-diabetic patients. Administered subcutaneously once a week, its potential lies in serving as a standalone therapy or part of a combination treatment to enhance weight loss, with prospects for expansion into other medical indications.
CT-996, a daily oral solution, is a small molecule GLP-1 receptor agonist currently in Phase-I, targeted at addressing obesity in individuals with and without type 2 diabetes.
CT-868, a Phase-II, daily subcutaneous injectable, is a dual GLP-1/GIP receptor agonist intended to cater specifically to type 1 diabetes patients dealing with overweight or obesity.
Under the terms delineated in the agreement, Roche is slated to transfer a cash consideration of USD 2.7 billion to the equity holders of Carmot upon the conclusion of the transaction. Additionally, contingent on the realization of certain milestones, Carmot's equity holders may receive payments amounting to a maximum of USD 400 million. Upon the finalization of the transaction, Roche will gain entry to Carmot's existing research and development portfolio, encompassing both clinical and pre-clinical assets. Simultaneously, Carmot, along with its workforce, will seamlessly integrate into the Roche Group, functioning as an integral component of Roche's Pharmaceuticals Division.
After the transaction is finalized, Roche will gain exclusive utilization of Carmot’s groundbreaking Chemotype Evolution discovery platform in metabolism. This partnership aims to fortify Roche’s research and development initiatives and expand its portfolio within cardiovascular and metabolic diseases. The completion of this transaction remains contingent upon the conclusion or termination of the waiting period as stipulated by the Hart-Scott-Rodino Antitrust Improvements Act of 1976, alongside other standard closing conditions. It is presently anticipated that the transaction will be finalized in the first quarter of 2024.
Pfizer and Valneva Complete Recruitment for Phase 3 VALOR Trial for Lyme Disease Vaccine Candidate, VLA15
Pfizer Inc. (NYSE: PFE) and Valneva SE (Nasdaq: VALN; Euronext Paris: VLA) disclosed on December 4, 2023, the conclusion of recruitment for the Phase 3 trial of the VLA15, a potential vaccine for Lyme disease, known as the Vaccine Against Lyme for Outdoor Recreationists (VALOR) (NCT05477524). This trial, expanding upon promising Phase 1 and 2 outcomes, encompasses both adult and pediatric participants. Its primary objective is to validate the efficacy, safety, lot consistency, and immunogenicity of VLA15.
Initiated in August 2022, the VALOR trial has successfully registered 9,437* participants aged five and above, spanning locations highly affected by Lyme disease in the U.S., Europe, and Canada. Within the initial year, participants undergo a primary series, receiving three doses of either VLA15 or a saline placebo.
As of now, there are no approved vaccines for Lyme disease. VLA15 stands as the most advanced candidate in clinical development for this purpose, currently undergoing two Phase 3 trials. This investigational vaccine utilizes a multivalent protein subunit approach, focusing on the outer surface protein A (OspA) of Borrelia burgdorferi—the bacteria responsible for Lyme disease. OspA, a surface protein expressed by the bacteria when within a tick, plays a crucial role. Blocking OspA hampers the bacterium's ability to exit the tick and initiate infection in humans.
We are pleased that the Phase 3 trial recruitment is complete. Lyme disease is the most prevalent vector-borne infectious disease in the United States and Europe, can sometimes even lead to long-lasting consequences,” said Annaliesa Anderson, Ph.D., Senior Vice President and Head, Vaccine Research and Development, Pfizer. “If approved, a vaccine could prevent the disease and ease the burden of acute, severe, and sometimes persistent consequences in both adults and children. We look forward to progressing the trial with the goal of submitting a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) and Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in 2026, subject to positive data.
Juan Carlos Jaramillo M.D., Chief Medical Officer of Valneva, said: “The completion of enrollment is indeed an important milestone in the development of a potential vaccine for Lyme disease. VLA15 has the potential to address a high need in North America and Europe, as it has been designed to offer coverage for the most common circulating types of Borrelia bacteria that cause Lyme disease in these regions. We’re excited about the ongoing trials and the progress towards potentially offering a vaccine against this disease, which can result in debilitating sequelae and excessive healthcare usage".
The VLA15 candidate has shown robust immune responses and maintained a positive safety record in both preclinical and clinical trials, across various doses and age brackets. Independent oversight by the Data Safety Monitoring Board (DSMB) noted no serious adverse events (SAEs) related to the vaccine and raised no safety concerns. Additionally, a fully enrolled second Phase 3 trial (C4601012) is underway to specifically assess the safety profile of VLA15 in the pediatric population, aiming to bolster existing evidence.
The anticipated conclusion of the VALOR trial is set for the conclusion of 2025. Pfizer and Valneva initiated a collaboration agreement in April 2020 to jointly develop VLA15, with subsequent adjustments to the terms within this arrangement made in June 2022.
Lyme disease, a systemic infection, results from Borrelia burgdorferi bacteria transmitted to humans through the bites of infected Ixodes ticks. Regarded as the predominant vector-borne illness in the Northern Hemisphere, the precise incidence of Lyme disease remains uncertain. However, estimates suggest it impacts around 476,000 individuals annually in the U.S. and about 129,000 in Europe. Globally, several major pharmaceutical and biotech companies are actively contributing to the development of Lyme disease therapies through research, clinical trials, and innovative treatment approaches. Pfizer and Valneva are currently leading the therapeutics segment, followed by several other key players.
Merck Strengthens Oncology Portfolio Through Commercialization Agreement With Abbisko for Phase III Asset, Pimicotinib
Merck revealed on December 04, 2023, an agreement with Abbisko Therapeutics Co. Ltd. (Shanghai, China), securing an oncology portfolio license for the therapeutics candidate, pimicotinib (ABSK021). Pimicotinib is presently undergoing Phase III evaluation for treating Tenosynovial Giant Cell Tumors (TSGCTs). This licensing agreement authorizes Merck to market pimicotinib in mainland China, Hong Kong, Macau, and Taiwan, with an additional option for global distribution. The licensing agreement between Merck and Abbisko is poised to redefine competition within the TSGCTs market.
Abbisko intends to further the development of pimicotinib, while Merck holds the choice to co-develop the drug in extra applications based on specific conditions. Merck is set to furnish Abbisko with an initial payment of $70 million, and upon opting for the option, will also offer an option fee. Abbisko stands to gain extra payments upon meeting specific regulatory and commercial milestones, along with tiered royalties in double digits based on Merck's net sales.
We have the opportunity through our partnership with Abbisko to deliver a first-in-class treatment for a critically underserved patient population in China and potentially beyond,” said Andrew Paterson, Chief Marketing Officer for the Healthcare business sector of Merck. “Pimicotinib provides an opportunity to address a significant unmet medical need and for us to expand our commercial footprint in oncology in China, the second-largest pharmaceutical market in the world.
The collaboration with Merck is an important milestone in advancing the global commercialization process of pimicotinib, and provides a new model for the commercialization path of Abbisko’s pipeline in the future,” said Dr. Xu Yao-chang, Chairman of Abbisko Therapeutics. “We are pleased to collaborate with a leading multinational pharmaceutical company, jointly accelerating the global approval and commercialization pace of pimicotinib, and striving to bring new treatment options to patients as soon as possible.
Pimicotinib, an orally administered, remarkably selective, and potent small-molecule colony stimulating factor-1 receptor (CSF-1R) antagonist, is undergoing assessment in a worldwide Phase III clinical trial as a potential treatment for Tenosynovial Giant Cell Tumors. In China, there are currently no approved drugs for this condition, and in the U.S., only one medication has gained approval.
Abbisko Therapeutics independently developed Pimicotinib (ABSK021), a new, orally administered, remarkably selective, and powerful small-molecule CSF-1R inhibitor. Pimicotinib has secured breakthrough therapy designations (BTD) from both the China National Medical Products Administration (NMPA) and the U.S. Food and Drug Administration (FDA), along with a priority medicine (PRIME) designation from the European Medicines Agency (EMA) for addressing patients with Tenosynovial Giant Cell Tumors unsuitable for surgery.
In a recent Phase Ib trial, pimicotinib exhibited sustained and clinically significant antitumor effects, showing an overall response rate of 87.5% (28 out of 32 patients, including 3 complete responses) among those receiving the 50mg QD dose at the one-year follow-up, as assessed by the Independent Review Committee based on Response Evaluation Criteria in Solid Tumors v1.1 (RECIST 1.1). The ongoing Phase III MANEUVER trial, a randomized, double-blind, placebo-controlled study, is assessing the effectiveness and safety of pimicotinib at a 50 mg QD dose in patients with unresectable Tenosynovial Giant Cell Tumors.
Apart from TGCT, Abbisko Therapeutics is actively investigating the potential of pimicotinib in various solid tumors, exploring its efficacy across multiple indications. Additionally, Abbisko has received approval from the NMPA to initiate Phase II clinical trials in chronic graft-versus-host disease and advanced pancreatic cancer.
AbbVie to Acquire ImmunoGen, including its Flagship Cancer Therapy ELAHERE, Expanding Solid Tumor Portfolio
AbbVie and ImmunoGen have reached a definite agreement where AbbVie will acquire ImmunoGen, including its main cancer treatment ELAHERE®, known for its effectiveness in treating platinum-resistant ovarian cancer. This acquisition is set to bolster AbbVie's presence in solid tumor therapies significantly. In addition to ELAHERE®, ImmunoGen's pipeline of advanced ADCs aligns well with AbbVie's existing programs and enhances its ADC platform.
Under the deal, AbbVie will buy all outstanding shares of ImmunoGen for $31.26 per share in cash, valuing ImmunoGen at around $10.1 billion. Both companies' boards of directors have given their approval for this acquisition, expected to conclude in mid-2024, pending ImmunoGen shareholder consent, regulatory green lights, and other customary closing terms.
Richard A. Gonzalez, Chairman and CEO of AbbVie, emphasized that this acquisition underscores their commitment to long-term growth, diversifying their oncology pipeline for solid tumors and hematologic malignancies. He believes this union holds promise to reshape cancer care standards.
The addition of ImmunoGen's portfolio is anticipated to contribute significantly to AbbVie's oncology revenue growth, especially with ELAHERE's potential in ovarian cancer treatment. ELAHERE, as the first targeted therapy demonstrating a substantial survival benefit in platinum-resistant ovarian cancer, presents AbbVie with a high-value medicine and room for expansion within the ovarian cancer market.
Mark Enyedy, President and CEO of ImmunoGen, expressed confidence in AbbVie's global infrastructure and expertise to expand ELAHERE's reach and maximize its potential as the sole approved ADC for ovarian cancer. He sees this consolidation as the culmination of ImmunoGen's decades-long commitment to pioneering ADCs for cancer patients.
ELAHERE, a groundbreaking ADC targeting folate receptor alpha (FRα), gained accelerated FDA approval in 2022 for treating specific ovarian cancers. ImmunoGen aims to secure full approval through ongoing trials, paving the way for broader applications in earlier therapy stages and larger patient groups over the next decade.
Moreover, ImmunoGen's pipeline, including IMGN-151 for ovarian cancer and Pivekimab sunirine for a rare blood cancer called Blastic plasmacytoid dendritic cell neoplasm (BPDCN), enriches AbbVie's oncology programs in various solid tumors and hematologic malignancies. IMGN-151, in Phase 1, possesses potential expansion possibilities into multiple solid tumor indications, while Pivekimab sunirine, in Phase 2, targets Blastic plasmacytoid dendritic cell neoplasm and has received FDA breakthrough therapy designation.
This acquisition represents a strategic move for AbbVie to bolster its position in the oncology landscape, offering promising treatments and expanding its capabilities in addressing different cancer types.
FDA Grants Orphan Drug Designation to LP-284 for High-Grade B-Cell Lymphomas
Lantern Pharma has announced that the U.S. Food and Drug Administration (FDA) has given LP-284 Orphan Drug Designation for treating high-grade B-cell lymphoma that includes MYC and BCL2 rearrangements.
High-grade B-cell lymphoma (HGBL) is an uncommon and aggressive type of B-cell non-Hodgkin's lymphoma (NHL) lacking a well-established standard treatment. The initial approach often involves chemo-immunotherapies like R-CHOP or DA-R-EPOCH. Yet, about 20-30% of HGBL patients cease responding to these therapies, leading to disease progression. For those with relapsed or refractory (R/R) disease, survival forecasts range from 8.6 to 16 months (Laude et al., 2021). This highlights the urgent need for innovative and effective treatments to address HGBL and enhance patient outcomes.
LP-284, a new small molecule agent by Lantern, disrupts cancer cell DNA, resulting in their demise. Lantern is developing LP-284 for various aggressive B-cell NHLs, including MCL and HGBL, where preclinical models have demonstrated strong anti-tumor activity. The progression of LP-284 from initial RADR® A.I. insights to specific lymphoma subtype selection, late-stage IND enabling studies, and the start of initial human trials occurred in roughly 2.5 years.
Panna Sharma, Lantern Pharma's President & CEO, highlighted the significance of obtaining Orphan Drug Designation for LP-284, emphasizing their data-driven approach to oncology drug discovery and development. He mentioned positive preclinical data showcasing LP-284's potent anti-tumor effects as a standalone treatment and in combination with the FDA-approved lymphoma-targeting antibody Rituximab in HGBL. These findings are critical given the high relapse rates and unfavorable prognoses in most HGBL patients. He noted that this marks the second Orphan Drug Designation (ODD) for LP-284 by the FDA, with the initial designation granted in January 2023. Combining this recent ODD for LP-284 with the previous one, a total of five orphan designations have been conferred upon Lantern, including three for their drug candidate LP-184. These designations significantly benefit their business model, offering seven years of market exclusivity and eligibility for expedited drug development programs. They aim to leverage these designations to further discussions with biopharma companies for partnerships and collaborative development opportunities.
The FDA's Office of Orphan Products Development grants ODD to drugs targeting safe and effective treatments for rare diseases or conditions affecting fewer than 200,000 people in the United States. ODD provides various advantages to drug developers, such as market exclusivity for seven years post FDA approval, tax credits for qualified clinical trials, waived marketing registration application fees, reduced annual product fees, clinical protocol assistance, and qualification for expedited development programs.
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