KEYTRUDA has received approval for the adjuvant treatment of renal cell carcinoma in the United States, the European Union, Japan, and various other global regions. This approval is based on disease-free survival (DFS) data obtained from the KEYNOTE-564 study, initially presented at the 2021 ASCO Annual Meeting. Merck is presently collaborating with health authorities to integrate overall survival (OS) data into the comprehensive prescribing information for KEYTRUDA. Merck’s extensive clinical development initiative in RCC spans diverse scenarios, encompassing both adjuvant and advanced disease settings. This initiative involves the use of KEYTRUDA either as a standalone treatment or in combination with WELIREG (belzutifan, Merck’s oral hypoxia-inducible factor-2 alpha [HIF-2α] inhibitor), LENVIMA (lenvatinib, a multi-targeted VEGF TKI, in collaboration with Eisai), and quavonlimab (a CTLA-4 monoclonal antibody developed under an agreement with Akeso Inc.).
Bristol Myers Squibb Receives Positive CHMP Opinion for CAR T Cell Therapy Abecma in Earlier Lines of Therapy for Triple-Class Exposed Relapsed and Refractory Multiple Myeloma
Bristol Myers Squibb has disclosed that the Committee for Medicinal Products for Human Use (CHMP) within the European Medicines Agency (EMA) has put forth a recommendation for the approval of marketing authorization for Abecma® (idecabtagene vicleucel; ide-cel). This approval is specifically intended for treating adult patients dealing with relapsed and refractory multiple myeloma, having undergone at least two prior therapies, including an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody. The next step involves the European Commission (EC), responsible for approving medicines in the European Union (EU), reviewing this CHMP recommendation.
“We view the favorable CHMP opinion as a significant advancement in making our groundbreaking anti-BCMA CAR T cell therapy, Abecma, more accessible to a broader patient population at an earlier stage in the multiple myeloma treatment process, with the aim of enhancing treatment outcomes,” commented Dr. Anne Kerber, Senior Vice President and Head of Late Clinical Development, Hematology, Oncology, Cell Therapy (HOCT) at Bristol Myers Squibb. “We anticipate collaborating with the European Commission to jointly pursue the common objective of providing innovative treatment alternatives to a larger number of patients facing persistent unmet medical needs.”
The CHMP has issued a favorable opinion based on the conclusive analysis of progression-free survival (PFS) derived from the pivotal Phase III KarMMa-3 study. This open-label, global, randomized, controlled trial compared Abecma with standard combination regimens in adults suffering from relapsed and refractory multiple myeloma. These individuals had undergone two to four prior lines of therapy, including an IMiD, a PI, and an anti-CD38 monoclonal antibody—comprising the three main therapy classes (triple-class exposed) for multiple myeloma. Additionally, they were refractory to their last treatment.
Results presented at the American Society of Hematology (ASH) Annual Meeting in December 2023 demonstrated a significant enhancement in PFS with Abecma compared to standard regimens. At a median follow-up of 30.9 months (range: 12.7-47.8), Abecma exhibited a median PFS of 13.8 months, as opposed to 4.4 months with standard regimens (HR: 0.49; 95% CI: 0.38-0.63). This represents a notable 51% reduction in the risk of disease progression or death associated with the use of Abecma.
FDA Approves Dupixent as First and Only Treatment Indicated for Children Aged 1 year and Older with Eosinophilic Esophagitis
The U.S. Food and Drug Administration (FDA) has approved the use of Dupixent® (dupilumab) in the treatment of pediatric patients aged 1 to 11 years, with a minimum weight of 15 kg, who are diagnosed with eosinophilic esophagitis (EoE). Dupixent now stands as the sole medication sanctioned in the U.S. specifically for addressing the needs of this patient demographic. This approval marks an extension from the initial FDA authorization in May 2022, which covered patients aged 12 years and older with a minimum weight of 40 kg, for the treatment of EoE. The FDA conducted a thorough evaluation of Dupixent for this expanded indication through Priority Review, a designation reserved for medications that demonstrate potentially significant enhancements in efficacy or safety for the treatment of serious conditions.
“Children suffering from eosinophilic esophagitis face substantial gaps in medical care. Despite available treatment choices, 40% of kids under 12 in the United States still endure symptoms of this condition. This approval reflects our dedication to providing solutions for young patients facing unmet needs, offering hope to those in a crucial stage where challenges in eating and maintaining weight directly affect their overall nutritional intake and development.” – Naimish Patel, M.D., Head of Global Development, Immunology and Inflammation at Sanofi
The FDA approval for eosinophilic esophagitis treatment is granted based on findings from the Phase III EoE KIDS trial, which consists of two parts (Part A and Part B). This trial assessed the effectiveness and safety of Dupixent in children aged 1 to 11 years with EoE. After 16 weeks, 66% of children receiving a higher dose of Dupixent through tiered dosing based on weight (n=32) achieved histological disease remission (≤6 eosinophils/high power field), the primary endpoint. In comparison, only 3% of those on placebo (n=29) achieved histological disease remission. The histological remission was sustained at week 52, with 53% (17 out of 32) of children treated with Dupixent in Parts A and B maintaining remission. Additionally, histological remission at week 52 was achieved by 53% (8 out of 15) of children who switched to Dupixent from placebo in Part B. Furthermore, children treated with Dupixent showed a more significant reduction in the proportion of days with one or more signs of EoE, based on the Pediatric EoE Sign/Symptom Questionnaire-caregiver version (PESQ-C), compared to those on placebo at the 16-week mark.
Juvena Therapeutics Receives FDA Orphan Drug Designation for JUV-161 for the Treatment of Myotonic Dystrophy Type 1
Juvena Therapeutics announced on January 23, 2024, that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug designation to its leading drug candidate, JUV-161. This investigational therapeutic is designed for treating Myotonic Dystrophy Type 1 (DM1), a rare, multi-systemic, autosomal dominant inherited disease and the most prevalent form of adult muscular dystrophy.
Juvena’s AI-driven drug discovery and development platform identified JUV-161, showcasing its capability to restore muscle fiber formation, mitigate muscle atrophy, boost muscle strength and endurance, and enhance metabolism across various animal models. Anticipated for initiation this year, human trials for JUV-161 involve the administration of an engineered human IGF-2 protein through subcutaneous injection.
Utilizing its platform, Juvena delves into thousands of proteins secreted by human stem cells, assessing their capacity to rejuvenate tissue equilibrium and transforming them into innovative biologic medications with life-saving potential. The company has successfully built an extensive proprietary multi-dimensional library of regenerative proteins. Leading Juvena’s preclinical pipeline for engineered biologics targeting various myopathies and metabolic disorders is JUV-161. Furthermore, Juvena has pinpointed several secreted protein candidates that elicit disease-modifying effects across diverse metabolic organs and therapeutic domains.
“People living with DM1 deserve safe, effective, and rejuvenating treatments that can repair and restore tissue health to improve muscle function and metabolism,” said Dr. Hanadie Yousef, Co-Founder and CEO of Juvena Therapeutics. “As we advance Juvena’s first biologic initially focused on the treatment of DM1, we look forward to exploring potential treatments for an entire class of disorders that remain major unmet medical needs.”
“Until treatments are available, DM1 will continue to progressively limit individuals’ strength and their ability to do everyday things like walking, talking, swallowing, and even breathing,” said Dr. Tanya Stevenson, CEO of the Myotonic Dystrophy Foundation. “We are excited about the unique approach Juvena Therapeutics is advancing because of its potential to safely promote muscle regeneration, improve metabolism, rejuvenate lives, and ultimately to more holistically address the disease.”
“FDA-approved biologics based on secreted proteins such as insulin, human growth hormone, and erythropoietin, can have life-changing impacts; however, the massive search power needed to systematically map this complex class of proteins has challenged the industry’s ability to continue discovering proteins that reverse disease in humans,” said Dr. Jeremy O’Connell, Co-Founder and Chief Scientific Officer of Juvena Therapeutics. “We are thrilled with the recognition of our lead candidate, JUV-161, as a potential addition to this class of drugs, and the success of Juvena’s platform in revolutionizing the study of secreted proteins as therapeutics.”
Myotonic Dystrophy Type 1 (DM1) impacts approximately 1 in 2,100 individuals and can manifest at any stage of life. Those grappling with Myotonic Dystrophy Type 1 encounter a diverse array of symptoms, encompassing muscle atrophy and weakness, myotonia characterized by delayed muscle relaxation, cataracts, irregularities in heart conduction and rhythm, impaired blood sugar control, and respiratory challenges. The pervasive nature of these symptoms underscores the complexity of managing Myotonic Dystrophy Type 1, highlighting the urgent need for effective treatments. Presently, the medical landscape grapples with a notable gap as there are no approved therapies specifically designed to address the complexities of Myotonic Dystrophy Type 1, intensifying the urgency and importance of ongoing research and clinical trials spearheaded by entities like Juvena Therapeutics. The potential success of these initiatives holds promise for transformative breakthroughs in treating this challenging and currently untreatable condition.
The ongoing clinical trial conducted by Juvena Therapeutics and its counterparts holds significant promise for revolutionizing the treatment landscape in the coming years. With a focus on advanced therapies, particularly in the field of myopathies and metabolic diseases, these trials aim to introduce groundbreaking treatments that could address previously unmet medical needs. By leveraging innovative biologics and regenerative proteins, Juvena, and its collaborators are poised to usher in a new era of therapeutic approaches, offering hope for improved outcomes and enhanced quality of life for patients. The potential success of these trials could reshape the treatment paradigm and set a precedent for transformative advancements in the broader field of therapeutics.
ENHERTU® (fam-trastuzumab deruxtecan-nxki) Granted Priority Review in the US for Patients with Metastatic HER2-positive Solid Tumors
On January 29, 2024, AstraZeneca and Daiichi Sankyo’s supplemental Biologics License Application (sBLA) for ENHERTU® (fam-trastuzumab deruxtecan-nxki) has been accepted and granted Priority Review in the US for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+) solid tumors who have received prior treatment or who have no satisfactory alternative treatment options. The grant of Priority Review comes after ENHERTU received Breakthrough Therapy Designation (BTD) in the United States in August 2023 for its application in metastatic HER2-positive solid tumors.
The ongoing development of ENHERTU represents a transformative shift in the therapeutics landscape for metastatic HER2-positive solid tumors. With promising results from trials like DESTINY-PanTumor02, this innovative treatment offers the potential for significant advancements in addressing the challenges associated with HER2-expressing metastatic cancers, heralding a new era in therapeutic approaches for improved patient outcomes.
The foundation for the supplemental Biologics License Application (sBLA) lies in the ongoing DESTINY-PanTumor02 Phase II trial, where ENHERTU showcased substantial and enduring responses. These responses translated into a clinically significant survival advantage for patients previously treated for HER2-expressing metastatic solid tumors, encompassing various cancer types such as biliary tract, bladder, cervical, endometrial, ovarian cancers, and others. The submission also incorporates data from complementary trials within the ENHERTU clinical development program, including DESTINY-Lung01 and DESTINY-CRC02, focusing on patients with HER2-positive IHC3+ tumors.
The safety profile noted throughout the trials remained consistent with previous clinical studies of ENHERTU, and there were no new safety concerns identified. The findings from the DESTINY-PanTumor02 trial were unveiled at the 2023 European Society for Medical Oncology Congress and concurrently published in the Journal of Clinical Oncology.
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Today’s Priority Review for the first tumor-agnostic submission for ENHERTU reflects the potential of this medicine to redefine the treatment of HER2-expressing cancers. Biomarkers for HER2 expression are already established in breast and gastric cancers, but we must now define them across tumor types. We will continue working closely with the FDA to bring this potential first tumor-agnostic HER2-targeted medicine and biomarker to patients as quickly as possible.”
Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: “The clinical benefit seen across HER2-expressing metastatic solid tumors in the DESTINY-PanTumor02 trial and ongoing data from the ENHERTU clinical development program continues to demonstrate the potential of this medicine beyond its approved indications. If approved, ENHERTU could become the first HER2-directed therapy and antibody drug conjugate with a tumor-agnostic indication, providing patients with a potential new treatment option.”
AstraZeneca and Daiichi Sankyo are collaboratively developing and commercializing ENHERTU, a HER2-directed antibody-drug conjugate (ADC) that has been meticulously engineered for its therapeutic properties. The supplemental Biologics License Application (sBLA) is undergoing evaluation through the Real-Time Oncology Review (RTOR) program and Project Orbis, initiatives established by the FDA to expedite the availability of safe and effective cancer treatments to patients. RTOR enables the FDA to assess certain components of an application prior to the submission of the complete application. Meanwhile, Project Orbis offers a structure for the simultaneous submission and review of oncology medicines, involving collaboration among international partners who participate in the program.
European Commission Authorises GSK’s Omjjara (Momelotinib)
On January 29, 2024, GSK plc (LSE/NYSE: GSK) revealed that the European Commission had granted marketing authorization for Omjjara (momelotinib). This medication, a once-a-day, oral inhibitor of JAK1/JAK2 and activin A receptor type 1 (ACVR1), has become the first approved treatment in the EU for disease-related splenomegaly (enlarged spleen) or associated symptoms in adult patients experiencing moderate to severe anemia. This authorization extends to individuals with primary myelofibrosis, post polycythaemia vera myelofibrosis, or post essential thrombocythaemia myelofibrosis, who are either JAK inhibitor naïve or have undergone treatment with ruxolitinib.
Momelotinib exhibits a distinct mechanism of action, possessing inhibitory effects on three crucial signaling pathways: Janus kinase (JAK) 1, JAK2, and activin A receptor, type I (ACVR1). The inhibition of JAK1 and JAK2 is anticipated to enhance constitutional symptom relief and reduce splenomegaly. Moreover, the suppression of ACVR1 results in a reduction of circulating hepcidin levels, potentially contributing to benefits associated with anemia.
The approval of momelotinib is grounded in the MOMENTUM pivotal phase III trial and a subgroup of adult patients experiencing moderate to severe anemia (hemoglobin <10 g/dL) from the SIMPLIFY-1 phase III trial. The MOMENTUM trial was structured to assess the safety and effectiveness of momelotinib compared to danazol for addressing and mitigating key manifestations of myelofibrosis in anemic, symptomatic individuals who had previous experience with JAK inhibitors. On the other hand, SIMPLIFY-1 was designed to investigate the efficacy and safety of momelotinib in comparison to ruxolitinib in myelofibrosis patients who had not undergone prior JAK inhibitor therapy. During these clinical trials, the prevailing adverse reactions observed included diarrhea, thrombocytopenia, nausea, headache, dizziness, fatigue, asthenia, abdominal pain, and cough.
In September 2023, the US Food and Drug Administration granted approval for momelotinib under the brand name Ojjaara. This approval is specifically for the treatment of intermediate or high-risk myelofibrosis in adults, encompassing primary myelofibrosis as well as secondary myelofibrosis (post-polycythaemia vera and post-essential thrombocythaemia), particularly in individuals with anemia.
Nina Mojas, Senior Vice President, of Oncology Global Product Strategy, GSK, said: “The challenges of living with myelofibrosis can be burdensome, and symptomatic patients can experience spleen enlargement, fatigue, night sweats and bone pain. Until now, there have been no options specifically indicated to treat these symptoms in patients who also experience anaemia. The authorisation of Omjjara brings a new treatment option with a differentiated mechanism of action to these patients in the EU.”
Francesca Palandri, MD, PhD, IRCCS S. Orsola-Malpighi, Bologna University Hospital, Italy, said: “The EU authorisation of Omjjara represents a meaningful advancement for eligible patients with myelofibrosis, and particularly for those with moderate to severe anaemia who need new treatment options that may reduce their disease-related burden. The availability of a single therapy for key manifestations of myelofibrosis is a clear step forward for eligible patients.”
Myelofibrosis is an uncommon form of blood cancer that disturbs the regular production of blood cells due to dysregulated JAK-signal transducer and activator of transcription protein signaling. Myelofibrosis is believed to impact approximately 1 in 10,000 individuals in the European Union. Around 40% of patients present with moderate to severe anemia at the time of diagnosis, and nearly all patients are anticipated to develop anemia as the disease progresses. Myelofibrosis patients dealing with anemia often necessitate supplementary supportive care, such as transfusions. Unfortunately, over 30% of individuals may discontinue treatment due to the challenges posed by anemia. Notably, patients dependent on transfusions tend to have a less favorable prognosis and experience a shortened overall survival. This underscores the significant burden that anemia imposes on the management and outcomes of myelofibrosis. Improved strategies for addressing anemia in this patient population are crucial for enhancing both the quality of life and the long-term prognosis of those affected by myelofibrosis.
