Orforglipron
- Generic Name
- Orforglipron
GSK and iTeos Terminate TIGIT Cancer Drug Development After Phase 2 Failure
• GSK and iTeos Therapeutics have discontinued development of belrestotug, their TIGIT-targeting immunotherapy, after it failed to significantly delay tumor progression in non-small cell lung cancer patients.
• The companies are terminating all ongoing trials, including a Phase 3 study, ending their four-year collaboration that began with GSK's $625 million upfront payment and potential $1.45 billion in milestone payments.
• iTeos is now conducting a strategic review to preserve capital, as the failure eliminates its most advanced drug candidate and represents another setback for TIGIT-targeting therapies in oncology.
Lilly's Oral GLP-1 Orforglipron Shows Promising Results in Phase 3 Trial
• Eli Lilly's once-daily oral GLP-1 receptor agonist, orforglipron, demonstrated statistically significant efficacy and a safety profile consistent with injectable GLP-1 medicines in a successful Phase 3 clinical trial.
• The development represents a potential breakthrough in diabetes and obesity treatment, offering patients a convenient pill alternative to injectable medications like Ozempic and Wegovy.
• Lilly CEO David A. Ricks emphasized that orforglipron could be "readily manufactured and launched at scale for use by people around the world," addressing growing global demand for GLP-1 therapies.
FDA Commissioner Makary Proposes New Approval Pathway for Rare Disease Drugs
• FDA Commissioner Marty Makary has announced plans for a new regulatory pathway to expedite approvals for rare disease treatments, potentially without requiring randomized controlled trials.
• The proposed "plausible mechanism" pathway would include conditional approvals for therapies with scientifically sound physiological rationales, coupled with a comprehensive patient surveillance system.
• Makary also addressed public distrust in health authorities, announcing plans to replace the self-reported VAERS system with a more robust "Health Information Exchange" to better monitor treatment complications.
Novartis Announces $23 Billion Investment to Expand US Manufacturing and R&D Footprint
• Novartis plans to invest $23 billion over five years to establish seven new facilities and expand three existing ones across the United States, enabling 100% end-to-end US production of key medicines.
• The expansion includes a $1.1 billion research hub in San Diego and new radioligand therapy manufacturing facilities in Florida and Texas, creating approximately 5,000 jobs directly and indirectly.
• This strategic investment reverses Novartis' recent US pullback and comes amid trade policy uncertainties, positioning the company to maintain its projected sales growth of +5% CAGR through 2029.
Roche and Zealand Pharma Forge $5.3 Billion Partnership to Develop Novel Obesity Treatments
• Roche has entered into a $5.3 billion collaboration with Zealand Pharma to co-develop petrelintide, a promising amylin analog for obesity treatment, both as monotherapy and in combination with Roche's incretin asset CT-388.
• The partnership includes upfront payments of $1.65 billion to Zealand Pharma, with profits and losses to be shared 50/50 in the US and Europe, while Roche gains exclusive commercialization rights for the rest of the world.
• Clinical data suggests petrelintide could deliver weight loss comparable to GLP-1 receptor agonists but with improved tolerability, potentially addressing unmet needs in the obesity market that is projected to affect 4 billion people globally by 2035.
Novo Nordisk Launches Home Delivery Service for Wegovy at $499 Monthly for Cash-Paying Patients
• Novo Nordisk introduces NovoCare Pharmacy, a direct-to-patient delivery service offering all Wegovy dose strengths at $499 per month for cash-paying and eligible commercially insured patients without coverage.
• The launch comes as Wegovy supply stabilizes, with FDA confirming Novo Nordisk can now meet market demand following previous shortages that limited new prescriptions since 2022.
• Currently, over 55 million Americans have coverage for weight management medicines, with 90% of insured Wegovy patients paying $0-$25 monthly for their prescriptions.
FDA Removes Ozempic and Wegovy from Shortage List, Sparking Legal Challenge from Compounding Groups
• The FDA has officially removed Novo Nordisk's semaglutide products, Ozempic and Wegovy, from its drug shortage list after being listed since 2022, signaling improved supply availability.
• Compounding groups have filed a lawsuit challenging the FDA's decision, arguing it was made without proper stakeholder consultation and despite ongoing supply challenges acknowledged by Novo Nordisk.
• The legal dispute highlights broader tensions between pharmaceutical manufacturers and compounding facilities over access to semaglutide for treating type 2 diabetes, obesity, and cardiovascular disease.
Novo Nordisk's Amycretin Shows Promising Weight Loss in Early Trials
• Novo Nordisk's amycretin, a unimolecular GLP-1 and amylin receptor agonist, demonstrated a 22% average weight reduction in obese or overweight patients over 36 weeks.
• The Phase 1b/2a trial of subcutaneous amycretin showed a favorable safety profile, with mainly mild to moderate gastrointestinal side effects reported.
• These results have boosted investor confidence in Novo Nordisk's obesity drug pipeline, especially after previous disappointments with other candidates.
• Amycretin combines GLP-1 and amylin receptor agonism in a single molecule, potentially offering a more effective approach to weight management.
Ascletis' Oral GLP-1RA ASC30 Shows Promising Results in Obesity Trials
• Ascletis Pharma's ASC30, a novel oral GLP-1 receptor agonist, demonstrated dose-proportional pharmacokinetics and a long half-life of up to 60 hours in a Phase Ia study.
• Interim Phase Ib results showed a 6.3% mean body weight reduction after 28 days, suggesting potential best-in-class characteristics for obesity treatment.
• ASC30 was generally well tolerated, with mainly mild to moderate gastrointestinal-related adverse events and no serious adverse events reported.
• Ascletis anticipates topline results from the Phase Ib multiple ascending dose trial by the end of March 2025, evaluating weight loss, safety, and pharmacokinetics.
Clinical Trial Industry Faces Complex Challenges in 2025: Adaptive Designs, Political Shifts, and Diversity Requirements
• Clinical trials are becoming increasingly complex and expensive as they target smaller patient populations and face stricter regulations, driving the need for smarter and more efficient trial designs.
• Political changes, including Trump's presidency, could lead to significant regulatory shifts in the clinical trial landscape, potentially affecting approval pathways and oversight mechanisms.
• New legislation like the Inflation Reduction Act is expected to impact trial initiations and drug development, while diversity guidelines from WHO, FDA, and EMA present both opportunities and challenges for patient recruitment.
Kailera's HRS9531 Shows Strong Phase II Weight Loss, Pfizer Cautious on Danuglipron
• Kailera Therapeutics' HRS9531, a dual GLP-1/GIP receptor agonist, demonstrated a 21.1% placebo-adjusted weight reduction in Phase II trials over 36 weeks.
• Pfizer CEO Albert Bourla expressed caution regarding their oral obesity candidate, danuglipron, despite plans for late-stage studies of the once-daily formulation.
• Kailera reported that 59% of patients on HRS9531 achieved at least 20% body weight loss, with no plateau observed, suggesting potential for greater efficacy with longer use.
• Pfizer abandoned a twice-daily danuglipron formulation due to toxicities, focusing on a once-daily version, but analysts remain divided on its prospects in the competitive obesity market.
Hengrui Pharma's HRS9531 Shows Promising Weight Loss in Phase 2 Obesity Trial
• Hengrui Pharmaceuticals and Kailera Therapeutics reported positive Phase 2 results for HRS9531, a GLP-1/GIP receptor dual agonist, in overweight or obese adults.
• Participants receiving the 8 mg dose of HRS9531 achieved a statistically significant 21.1% placebo-adjusted mean weight loss at 36 weeks.
• The trial demonstrated a favorable safety profile, with most adverse events being mild and gastrointestinal-related during dose titration.
• Hengrui is advancing HRS9531 into Phase 3 clinical trials for obesity and type 2 diabetes in China, with Kailera developing it globally as KAI-9531.
Eli Lilly's Zepbound Demonstrates Superior Weight Loss Compared to Novo Nordisk's Wegovy in Head-to-Head Trial
• Eli Lilly's Zepbound (tirzepatide) led to a 20.2% average weight loss, significantly outperforming Wegovy (semaglutide) at 13.7% in a 72-week clinical trial.
• The SURMOUNT-5 trial included overweight or obese adults without diabetes, showing Zepbound users experienced 47% more relative weight loss than Wegovy users.
• Zepbound, a dual GIP and GLP-1 receptor agonist, helped 31.6% of participants achieve at least 25% body weight loss, compared to 16.1% with Wegovy.
• The study's findings may influence treatment choices, with Zepbound potentially becoming a preferred option for greater weight loss outcomes, pending further data on tolerability.
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