Mar 25, 2022

Zachary Brennan Senior Editor Intarcia Therapeutics, once valued at more than $5 billion and attracting investors like the Bill & Melinda Gates Foundation, is now tussling with the FDA’s drug advisors over a last-ditch hearing to discuss the agency’s second rejection of the company’s lead type 2 diabetes drug since 2017. Back in December, Intarcia’s lawyer sent a letter to the FDA requesting that the agency set up a hearing to discuss this complete response letter, which laid out clinical deficiencies and device and product quality-related issues for the drug, known as ITCA 650. The agency in September granted the hearing but the schedule for it has yet to be established, and the agency is now making clear that this hearing is not its first priority. In a March 22 letter from Donna Katz of FDA’s Office of Chief Counsel to Matthew Warren, director of FDA’s Office of Scientific Integrity, Katz explained how CDER and Intarcia met via teleconference on March 14 but were unable to reach an agreement on the timing for CDER to submit its analysis and proposed order. Katz explains how ITCA 650 is a combo product, so CDRH officials will need to be involved. And not only are CDER employees still tied up with Covid-related work, but there’s another request for a hearing that will take precedence over Intarcia’s, as it was submitted earlier from Lexicon Pharmaceuticals. Lexicon received a CRL on March 3, 2021, for its sotagliflozin oral tablets for use as an adjunct to insulin therapy to improve glycemic control in adults with Type 1 diabetes. “CDER requests that any deadline established by the Commissioner regarding Intarcia’s hearing request be after any deadline established in that other hearing proceeding, and no earlier than July 29, 2022,” Katz wrote. She also requests later in the letter that Commissioner Rob Califf remain open to considering a request for an extension of time if needed due to unforeseen circumstances. For the ITCA 650 submission, which Katz noted was recently supplemented on Feb. 15, the road ahead looks murky, particularly as the company has been dealt three prior rejections of formal dispute resolution requests on top of the two CRLs. Intarcia’s CEO Kurt Graves told Endpoints News that the FDA diabetes division’s central non-approval claim against ITCA 650 is that it is the only GLP-1 “with a small and non-significant numeric imbalance in AKI events observed in a controlled clinical trial setting. The division has maintained that no other GLP-1 controlled clinical trials have ever observed similarly small AKI imbalances – even though they all have class labeled AKI Warnings and Precautions.” Graves pointed to Novo Nordisk’s AKI data for its diabetes drug Wegovy as FDA’s “own clinical review documents for the approval of Wegovy highlight an identical numeric imbalance in serious AKI events (not favoring drug) on Wegovy in their controlled trial package that supported Wegovy’s approval with labeled AKI Warnings. The only difference vs. ITCA 650 here is the FDA reviewer on ITCA 650 deemed the small and identical AKI imbalance a non-approval issue that couldn’t be labeled….where the review team on Wegovy (and all the other approved GLP-1s) deemed the AKI imbalances a labeling issue and approved the product/s with GLP-1 class labeled AKI warnings.” But the FDA previously raised questions about how trial participants who received ITCA 650 “sometimes resulted in prolonged hospitalization; complications observed in association with AKI events included dialysis and death.” A majority of the serious adverse events in participants randomized to ITCA 650 “appeared to be associated with vomiting, diarrhea, and dehydration, which are known adverse reactions associated with exenatide therapy, supporting a causal relationship between ITCA 650 and AKI,” FDA said. In addition, FDA said the company failed to provide sufficient assurances that its experimental diabetes drug is not linked to excess cardiovascular risks. And an FDA inspection of the Intarcia manufacturing facility also “identified deficiencies with the manufacturing practices for ITCA 650 that were not adequately addressed,” the agency said. Editor’s note: Article updated with new comments from Intarcia CEO Kurt Graves. AUTHOR Did the FDA change its mind about the class of cancer drugs known as PI3K? Whereas the agency had previously granted accelerated approvals to PI3K drugs, that option is apparently off the table for zandelisib, a candidate from MEI Pharma and Kyowa Kirin. For the companies, that means delaying a potential monotherapy launch from 2023 to 2026, according to analysts. There has been considerable heat around the drug class as Gilead yanked its PI3K inhibitor from the market, Incyte withdrew its NDA and the FDA put some of TG Therapeutics’ clinical work on its PI3K drug on hold, citing a potential increased risk of death. Keep reading Endpoints with a free subscription Unlock this story instantly and join 136,900+ biopharma pros reading Endpoints daily — and it's free. SIGN UP Max Gelman Editor Over the last 24 hours, something strange has happened in biotech: Public companies are raising money — and quite a lot, at that. Following Nasdaq’s closing bell Wednesday afternoon, three biotechs announced nine-figure raises in Ascendis Pharma, argenx and Apellis Pharmaceuticals, at a time where a bear market continues to bludgeon the sector. While unexpected, the cash sent a signal that companies can still pull together funds at the right opportunity, independent investor Brad Loncar told Endpoints News. Keep reading Endpoints with a free subscription Unlock this story instantly and join 136,900+ biopharma pros reading Endpoints daily — and it's free. SIGN UP Kyle LaHucik Associate Editor Bristol Myers Squibb was supposed to find out by this Sunday if the FDA was OK with a third approval for its Celgene-acquired, Acceleron-partnered anemia drug Reblozyl. But “a major amendment” is putting a bump in those plans. The Big Pharma will have to wait another three months, possibly as far out as June 27, to see if the agency will greenlight a supplemental nod. Bristol Myers wants Reblozyl — one of four drugs that the company anticipates could eventually rack up $4 billion in revenue per year — to also be a treatment for anemia in adults with non-transfusion-dependent (NTD) beta thalassemia. Read More March 23, 2022 07:02 AM EDTUpdated 02:54 PM Max Gelman Editor Next week, an FDA advisory committee will face an all-too familiar question: Should a drug for a fatal, neurodegenerative disease be approved despite less than conclusive efficacy data? It hasn’t been two full years since the panel faced a similar question in Biogen’s Alzheimer’s drug aducanumab. And it’s not unlike the 2016 debate over Sarepta’s first muscular dystrophy drug, either. In both scenarios, the FDA’s outside experts recommended against approval — unanimously in Biogen’s case — and in both scenarios, the agency greenlighted the drugs. Keep reading Endpoints with a free subscription Unlock this story instantly and join 136,900+ biopharma pros reading Endpoints daily — and it's free. SIGN UP Zachary Brennan Senior Editor The FDA sent over a quick rejection letter on Thursday to Eli Lilly regarding its anti-PD-1 antibody sintilimab, further crushing the hopes of any companies looking to bring cheaper follow-ons based only on Chinese data. The complete response letter (CRL) follows a nearly unanimous Oncologic Drugs Advisory Committee (ODAC) recommendation against sintilimab’s approval, which was intended as a first-line treatment for people with nonsquamous non-small cell lung cancer. The FDA also revealed at the meeting that the company submitted the application without consulting regulators before the trial concluded, and misrepresented interactions with the agency during its presentation. Keep reading Endpoints with a free subscription Unlock this story instantly and join 136,900+ biopharma pros reading Endpoints daily — and it's free. SIGN UP Nicole DeFeudis Editor Just over a year after it was initially approved, GSK’s HIV unit ViiV Healthcare has found yet another way to make Cabenuva’s label even more attractive. Cabenuva consists of two extended-release injectables: cabotegravir, which is developed by ViiV, and rilpivirine from J&J’s Janssen which is also marketed individually under the brand names Edurant and Rekambys. Previously, patients starting out on the long-acting HIV treatment were required to first take cabotegravir and rilpivirine by mouth for one month to assess their tolerability of the medicines before moving on to injections. Read More March 24, 2022 01:52 PM EDTUpdated 02:24 PM Jason Mast Editor When Longxing Cao arrived as a postdoc at the University of Washington in 2017, David Baker’s lab was already known as the leader in a niche field of designing new proteins from scratch. The idea was to replace, or supplement, the usual method for designing new proteins, i.e. borrowing from evolution. To come up with most new biologic therapies for cancer or infectious disease, for example, researchers generally filter out the best antibodies mice or humans develop against a virus or bits of a tumor. Maybe they’ll tinker with it a little. Keep reading Endpoints with a free subscription Unlock this story instantly and join 136,900+ biopharma pros reading Endpoints daily — and it's free. SIGN UP LOG IN