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Dupixent Significantly Reduced COPD Exacerbations In Second Positive Phase III Trial
The latest trial for Dupixent (dupilumab) in chronic obstructive pulmonary disease (COPD), called NOTUS, has delivered promising results. It showed a significant 34% reduction in COPD exacerbations, confirming earlier positive findings from the Phase III BOREAS trial. The study also revealed that Dupixent improved lung function rapidly within 12 weeks, and these improvements were sustained for 52 weeks.
NOTUS compared Dupixent to a placebo in adults already on maximal standard-of-care inhaled therapy (triple therapy) for COPD but experiencing uncontrolled symptoms and showing evidence of type 2 inflammation (blood eosinophils ≥300 cells per μL). These interim results were overwhelmingly positive for the primary endpoint, prompting consideration as the primary analysis for the trial. Sanofi and Regeneron intend to submit data from NOTUS and the successful Phase III BOREAS trial to the FDA by year-end.
“This marks a groundbreaking achievement, as Dupixent® (dupilumab) emerges as the first investigational biologic in COPD to demonstrate a noteworthy and clinically significant reduction in exacerbations across two Phase III trials. We are excited about the prospect of accelerating the delivery of Dupixent to patients facing unmet needs in a field where no notable advancements have been made in over a decade. These compelling results reinforce our confidence in the transformative potential of Dupixent in treating moderate-to-severe COPD. Recognizing the substantial challenges faced by patients with uncontrolled COPD, our commitment extends beyond Dupixent. Our ongoing second program in COPD, itepekimab, is progressing, with anticipated data availability in 2025. In the event of positive outcomes, both Dupixent and itepekimab could emerge as vital treatments for approximately 80% of individuals grappling with moderate-to-severe COPD characterized by recurrent exacerbations, said Naimish Patel, M.D., Head of Global Development, Immunology and Inflammation at Sanofi.
Earlier this year, the FDA acknowledged the groundbreaking potential of Dupixent by granting it the Breakthrough Therapy designation. This designation recognizes Dupixent as an add-on maintenance treatment for adult patients with uncontrolled COPD characterized by a history of exacerbations and an eosinophilic phenotype. The designation is based on the positive and promising results obtained from the BOREAS trial, emphasizing the clinical significance of Dupixent in addressing the needs of patients with a history of exacerbations and a specific eosinophilic phenotype in COPD.
Sanofi and Regeneron have submitted an application to the European Medicines Agency for the review of Dupixent as a potential treatment for uncontrolled COPD with type 2 inflammation. The application draws on data from the BOREAS trial. Simultaneously, ongoing discussions with regulatory bodies worldwide are in progress. It’s important to note that the safety and efficacy of Dupixent in COPD are currently the subject of clinical investigation and have not yet undergone evaluation by any regulatory authority.
Sosei Heptares to Regain Full Ownership of GSK4381406, a Clinic-ready, First-in-Class Oral GPR35 Agonist for Inflammatory Bowel Disease
Sosei Group Corporation has begun talks with GSK to reclaim complete ownership of GSK43814061. This novel oral GPR35 agonist is currently in development as a potential groundbreaking treatment for Inflammatory Bowel Diseases (IBD) under a Global Collaboration and License Agreement with GSK. GPR35, a crucial orphan G protein-coupled receptor with a known genetic link to IBD, presents a promising avenue to address the substantial unmet needs of millions of IBD patients globally.
Sosei Heptares employed its exclusive structure-based drug design (SBDD) platform to create GSK4381406, subsequently licensing it to GSK in 2020. In collaboration, Sosei Heptares and GSK have progressed GSK4381406 through a joint development initiative, producing encouraging mechanistic, preclinical, and safety data that indicates its potential to enhance barrier function and alleviate visceral pain in gastrointestinal conditions like ulcerative colitis and irritable bowel syndrome.
The utilization of this data empowered Sosei Heptares and GSK to secure approval from the UK Medicines and Healthcare Products Regulatory Agency in mid-2023 for the initiation of first-in-human studies on GSK4381406. Subsequent to a strategic shift in GSK’s immunology research approach and leadership, the company opted to deprioritize and cease the development of GSK4381406. Importantly, this decision was not influenced by any scientific, preclinical, or safety concerns related to GSK4381406. As outlined in the 2020 agreement between the two companies, Sosei Heptares has the privilege, with no upfront payment, to reclaim complete ownership of the GSK4381406 program. This includes all associated intellectual property initially licensed by Sosei Heptares to GSK, along with preclinical data generated during the collaborative partnership. In the event that GSK4381406 achieves commercial availability, GSK is entitled to a low single-digit royalty from Sosei Heptares on the net sales of the product.
Chris Cargill, President & CEO of Sosei Heptares, expressed enthusiasm about reclaiming ownership of GSK4381406 from GSK. He highlighted the program’s promising preclinical data, indicating its potential as a novel therapy for inflammatory bowel disease (IBD), and mentioned its imminent entry into a Phase I clinical trial.
AstraZeneca Gains Rights to Usynova’s KRAS Inhibitor in Deal Worth Almost $420M
AstraZeneca has bolstered its oncology pipeline with the acquisition of a small-molecule KRAS inhibitor, UA022, from Chinese biotech Usynova. The upfront payment for the licensing agreement amounts to $24 million. UA022 is designed to target the KRASG12D mutation and is currently undergoing preclinical development. As part of the exclusive worldwide license, AstraZeneca commits to potential milestone payments of up to $395 million in development and commercial achievements, along with royalties on future sales.
Assuming UA022 advances to the market, it would be in line with the pioneering KRAS inhibitors, Lumakras (sotorasib) from Amgen and Krazati (adagrasib) from Mirati. These inhibitors have been granted approval as second-line treatments for KRAS-mutated non-small cell lung cancer (NSCLC). Notably, Lumakras and Krazati target the KRAS G12C mutation prevalent in lung cancer, while UA022 is tailored to address the G12D mutation, which is more frequently associated with diseases like pancreatic and colorectal cancers.
Dr. Hu Tao, the co-founder and CEO of Usynova (Yousen Jianheng Biopharmaceutical), stated that KRAS G12D stands out as the predominant KRAS mutation in cancer, comprising approximately 26% of all KRAS mutations. Despite its prevalence, there are currently no approved drugs designed to target this specific mutation.
As per Usynova’s findings, UA022 exhibits strong anti-cancer properties in laboratory assessments, displaying favorable oral bioavailability and a “promising” safety profile. By entering into the licensing agreement, AZ aligns itself with a distinguished cohort of enterprises pursuing this target, including Mirati—poised to integrate into Bristol-Myers Squibb pending a $5.8 billion acquisition—and other contenders such as Revolution Medicines, Quanta Therapeutics, and Roche/Chugai.
SpringWorks Therapeutics Announces FDA Approval of OGSIVEO™ (nirogacestat) for the Treatment of Desmoid Tumors
On November 27, 2023, SpringWorks Therapeutics, Inc. (Nasdaq: SWTX) announced that the US Food and Drug Administration (FDA) has approved OGSIVEO™ (nirogacestat), an oral gamma-secretase inhibitor, for the treatment of adult patients with progressing Desmoid Tumors who require systemic treatment. The FDA previously granted Breakthrough Therapy, Fast Track, and Orphan Drug Designations to nirogacestat for the treatment of Desmoid Tumors.
“Our team is honored to deliver the first FDA-approved therapy for patients with Desmoid Tumors. This community has been waiting for an effective treatment that not only shrinks their tumors but also significantly improves pain, which is the most debilitating symptom reported by people living with Desmoid Tumors,” said Saqib Islam, Chief Executive Officer of SpringWorks. “We are pleased with the broad label, which includes all progressing adult patients and specifically references improvement in pain, and believe OGSIVEO has the potential to become the new standard of care for people living with these devastating tumors. This is a watershed moment for the desmoid tumor community, and we would like to extend our gratitude to the patients, families, investigators, and advocacy groups involved in the journey to making OGSIVEO available in the U.S.”
“Today is an extraordinary day for the desmoid tumor community. This approval is the culmination of a collaborative effort between the patient community, academia and the biopharmaceutical industry, who worked together with tenacity and persistence to advance promising science,” said Jeanne Whiting, Executive Director Emeritus and Co-Founder of the Desmoid Tumor Research Foundation. “Our hope is that patients and their families will benefit from greater awareness of Desmoid Tumors, faster diagnoses, and better outcomes now that there is an approved and effective treatment.”
The FDA approval of OGSIVEO is based on the results from the Phase 3 DeFi trial, which were published in the March 9, 2023 edition of the New England Journal of Medicine. OGSIVEO met the primary endpoint of improving progression-free survival (PFS), demonstrating a statistically significant improvement over placebo with a 71% reduction in the risk of disease progression (hazard ratio (HR) = 0.29 (95% CI: 0.15, 0.55); p< 0.001).
OGSIVEO demonstrated a safety and tolerability profile that was well-handled. Among patients treated with OGSIVEO, the most frequently observed adverse events (>15%) included diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea.
OGSIVEO will be accessible for ordering in the United States through a specialty pharmacy and distributor network within a span of five to ten business days. SpringWorks anticipates submitting a Marketing Authorization Application for OGSIVEO targeting Desmoid Tumors to the European Medicines Agency during the initial half of 2024.
OGSIVEO is not approved for treating any other condition in the United States, nor has it received authorization for any indication in other jurisdictions by any health authority. Additionally, SpringWorks is investigating nirogacestat as a prospective treatment for individuals diagnosed with ovarian granulosa cell tumors. Furthermore, in collaboration with industry and academic leaders, SpringWorks is exploring its potential for treating patients with multiple myeloma through various B-cell maturation agent (BCMA) combination therapy regimens.
Desmoid Tumors, also known as aggressive fibromatosis or desmoid fibromatosis, are uncommon soft tissue tumors characterized by their aggressive and locally invasive nature. These tumors have the potential to be severe and debilitating, occasionally posing a life-threatening risk when they affect vital structures. Typically detected in individuals aged 20 to 44 years old, Desmoid Tumors exhibit a higher incidence, around two to three times more frequent, among females. Estimates suggest approximately 1,000 to 1,650 new cases are diagnosed annually in the United States. While Desmoid Tumors don’t spread to other parts of the body, they present recurrence rates as high as 77% following surgical removal. Experts specializing in Desmoid Tumors and treatment guidelines currently advocate for systemic therapies as the primary intervention, suggesting them over surgery for most tumor locations requiring treatment.
Innovative efforts within pharmaceutical and biotech sectors are propelling research and development, aiming to revolutionize the treatment landscape for Desmoid Tumors. Companies like SpringWorks Therapeutics are at the forefront of improving Desmoid Tumors treatment outlook. Collaborative initiatives and novel therapeutic approaches are actively being explored to improve patient outcomes and expand available treatment options.
Arcturus Therapeutics Receives Orphan Drug Designation from the US FDA for ARCT-032 for the Treatment of Cystic Fibrosis
Arcturus Therapeutics Holdings Inc. (NASDAQ: ARCT), referred to as “Arcturus,” announced on November 27, 2023, that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to their product candidate ARCT-032, intended for the treatment of Cystic Fibrosis (CF).
“Orphan Drug Designation is a very important regulatory milestone in our development plan for ARCT-032,” said Joseph Payne, President, and Chief Executive Officer of Arcturus Therapeutics. “We are executing diligently to accelerate ARCT-032 as a potential new treatment option for people with Cystic Fibrosis.”
ARCT-032 employs Arcturus’ LUNAR® lipid-mediated aerosolized platform for administering CFTR messenger RNA to the lungs. This approach aims to introduce a functional CFTR mRNA copy into the lungs of individuals with CF, potentially reinstating CFTR activity and alleviating the subsequent effects contributing to progressive lung disease. The ARCT-032 program is backed by preclinical evidence in rodents, ferrets, and primates, showcasing the restoration of CFTR expression and function in human bronchial epithelial cells.
The first CF patient in the Phase 1b study successfully completed two administrations of ARCT-032. As per the update, Arcturus Therapeutics is set to share interim Phase 1b data in H1 2024.
As per DelveInsight’s assessment, the estimated Cystic Fibrosis diagnosed prevalent cases in the 7MM were 65,000+ cases in 2021. Among the 7MM, the highest total diagnosed prevalent cases of Cystic Fibrosis were accounted by the US in 2021 (32,100 cases), which are expected to show a rise in the future. Cystic Fibrosis, a globally prevalent disease, significantly curtails life expectancy. This condition arises from mutations within the Cystic Fibrosis transmembrane conductance regulator (CFTR) gene, resulting in a diminished or absent CFTR protein and its functionality within the airways. Consequently, there’s a notable decrease in chloride transport, disrupting the equilibrium of airway surfaces. This disturbance renders CF mucus challenging to clear, obstructing air passages and precipitating infections, inflammation, respiratory failure, and potentially life-threatening complications.
The current array of approved CFTR modulator therapies aims to enhance CFTR channel function, intending to alleviate symptoms associated with the condition. However, their effectiveness varies among individuals due to the specific mutations underlying their Cystic Fibrosis. This variability poses a challenge, leaving some individuals inadequately responsive to these therapies, thereby requiring novel approaches tailored to address the diversity of CF mutations and their distinct impacts on CFTR function.
Major pharmaceutical companies such as Arcturus Therapeutics, among others, are at the forefront of advancing Cystic Fibrosis treatment, investing heavily in innovative therapies and precision medicine. Ongoing research focuses on developing targeted therapies addressing specific genetic mutations, aiming to enhance efficacy and minimize side effects. Collaborative efforts between academia, biotech firms, and healthcare providers are accelerating the development of novel treatments, promising improved quality of life and extended survival for individuals with Cystic Fibrosis.
Alladapt Immunotherapeutics Receives FDA Fast Track Designation for ADP101 for the Treatment of Mono- and Multi-Food Allergies
Alladapt Immunotherapeutics announced on November 22, 2023, that their investigational multi-food oral immunotherapy (mOIT), ADP101, received Fast Track Designation from the U.S. Food and Drug Administration (FDA). ADP101 represents the forefront in the development of multi-food OIT pharmaceutical candidates, aiming to address allergy to several significant food allergens simultaneously.
The Fast Track Designation grant letter from the FDA signifies their support for the accelerated development of ADP101 as a therapy for food allergies. This includes its use in treating both multiple food allergies and single food allergies in children aged 4-17 with confirmed allergies to any of the 15 foods contained in the drug product: almond, cashew, chicken egg, codfish, cow milk, hazelnut, peanut, pecan, pistachio, salmon, sesame seed, shrimp, soy, walnut, and wheat.
The Fast Track designation granted to ADP101 stemmed from findings in Alladapt’s Phase 1/2 Harmony trial (NCT04856865), which aimed to assess ADP101’s efficacy and safety in inducing desensitization among individuals with either single or multiple food allergies. Data presented at the 2023 European Academy of Allergy & Clinical Immunology Congress and the 2023 American College of Allergy, Asthma, and Immunology Annual Meeting showcased ADP101’s ability to elicit dose-dependent, clinically significant responses as a multi-OIT food allergy desensitization therapy. The study also highlighted its favorable safety and tolerability profile, particularly in pediatric patients allergic to one or more of the food sources in the product. Alladapt is concurrently conducting the Encore Study, an open-label extension of the Harmony trial aimed at evaluating the long-term utilization of ADP101 among individuals with mono- and multi-food allergies.
Ashley Dombkowski, Ph.D., Chief Executive Officer and Co-Founder of Alladapt, said, “The FDA’s decision to grant ADP101 Fast Track Designation signifies an important milestone for people suffering from the substantial burden of food allergy, which requires constant, meticulous avoidance of all consumption or contact with allergens. Our team is thrilled to be at the forefront of developing a new treatment that addresses such a huge unmet need. We are excited to collaborate even more closely with the FDA as we move ahead to expedite development of this important therapy.”
As per DelveInsight, the total Food Allergy prevalent cases in the 7MM, Canada and China were 285,039,654 in 2021. These cases are set to increase in the upcoming years. At present, there are no FDA-approved Oral Immunotherapy (OIT) treatments for addressing allergies to multiple foods or those beyond peanuts. An independent study conducted over a year, involving patients seeking treatment for food-induced allergic reactions in the emergency department, revealed that 93% of cases involved individuals allergic to multiple foods or foods other than peanuts, while only 6.6% were solely allergic to peanuts. These findings underscore the urgency for interventions capable of addressing a wide spectrum of allergens in both variety and severity.
In the realm of allergy treatment, pharma giants like Alladapt Immunotherapeutics, among others are actively innovating, and dedicating resources to develop advanced immunotherapies and precision medicines. Collaborations between pharmaceutical firms and research institutions drive the creation of personalized allergy treatments tailored to individual patient profiles, aiming to mitigate allergic reactions effectively. Cutting-edge technologies and targeted therapies are being explored, offering promising avenues to alleviate symptoms and enhance the quality of life for allergy sufferers.