Bitopertin

iStock, Nuthawut Somsuk UniQure’s planned third-quarter submission for its Huntington’s disease gene therapy may be a harbinger of a more flexible FDA under acting commissioner Kyle Diamantas—but how long will it last? And how can companies be sure these positive decisions won’t just be reversed? Things don’t always go more smoothly when the boss is away, but that seems to be the case with the current state of play at FDA. While recording BioSpace ’s weekly podcast on Tuesday, I observed that there seems to be more alignment between biotech companies and the FDA of late. Not 24 hours later, uniQure hammered home that point, announcing that the FDA would now accept a regulatory filing for its Huntington’s disease gene therapy based on three-year data from its Phase 1/2 trial—something the agency refused to do late last year. “Get in line – uniCure [sic] latest to benefit from FDA U-turn: Back to rare disease regulatory baseline,” Don Fink, a regulatory consultant and former FDA’er, wrote Thursday on LinkedIn . Sure enough, uniQure’s news follows similarly upbeat announcements from Disc Medicine , Sanofi , Replimune and more. Last week, Disc revealed that the FDA has agreed that its current Phase 3 trial can support another regulatory filing for bitopertin, its rare blood disease drug that was rejected in February. Sanofi announced a new approval for its type 1 diabetes drug Tzield after reportedly requesting the agency revoke the Commissioner’s National Priority Voucher (CNPV) the application was awarded. And Replimune said on May 29 that it would resubmit its twice-rejected cancer immunotherapy after what CEO Sushil Patel called “collaborative dialogue” with the FDA “towards finding a meaningful path forward” for the company’s melanoma asset. In a note the same day, BMO Capital Markets noted that that RP1’s “third submission may reflect recent changes at FDA including departure of Commissioner [Marty] Makary.” With the FDA’s food chief Kyle Diamantas now serving as acting commissioner, “we believe the current FDA, largely in caretaker mode, appears to be more flexible on regulatory paths for applications where concerns were previously raised,” William Blair wrote in a Wednesday note following uniQure’s news. Indeed, while the FDA is still sorely lacking steady leadership, it seems the current state of affairs is working out better for the industry than the heavy-handed style of its now-departed chiefs. Both Makary and former Center for Biologics Evaluation and Research (CBER) director Vinay Prasad had been publicly critical of uniQure’s AMT-130. In the case of Repliume, BMO analysts initially suspected the “final hour shakeup” that led to rejection was due to Prasad, who they wrote in a July 22 note “has previously been critical of the approvability of uncontrolled data.” It was later revealed , however, that then-Oncology Center of Excellence director Richard Pazdur had intervened in the decision. As for Sanofi, former acting Center for Drug Evaluation and Research (CDER) Director Tracy Beth Høeg reportedly disagreed with FDA reviewers that the drug’s label should be expanded, prompting the company’s request to withdraw the drug from the CNPV program. Høeg also left the FDA shortly after Makary, while Pazdur unexpectedly retired late last year. Complete response letters UniQure, Replimune shares rise as FDA’s Makary exits, but path forward unchanged After devastating regulatory setbacks last year, shares of uniQure and Replimune rose on the news that FDA Commissioner Marty Makary is leaving. But analysts don’t expect much relief, no matter who helms the agency. May 13, 2026 · 3 min read · Annalee Armstrong Read more Meanwhile, Diamantas is getting rave reviews, having “earned the respect of career staff and the FDA stakeholder community,” Scott Faber, senior vice president of the Environmental Working Group, told STAT News on May 26. “He’s a natural leader, but he isn’t going to rush to the cameras.” This is a net positive on its own. Makary and Prasad continuously stirred up controversy with media appearances. This was never more evident than when Makary, during an interview with CNBC in February, appeared to malign AMT-130 . “There was a product where the researchers drilled a burr hole, literally a hole, in people’s skulls” to directly inject a drug candidate into patients’ brains, Makary said during the interview. “At the end of the randomization period, it was found no benefit, and yet this is one of the drugs that we were pressured to approve.” While Makary did not name a specific product, it was largely accepted that he was speaking about AMT-130 and uniQure’s stock crashed accordingly. Prasad also spoke to the media about uniQure, refuting the company’s characterization of the potential sham-controlled study during a call with reporters in early March. Diamantas, on the other hand, met earlier this month with rare disease groups, reportedly to mend fences with a sector that has faced a much more stringent FDA of late. Jeff Allen, CEO of Friends of Cancer Research, described the meeting to Reuters as a “breath of fresh air.” More importantly, Diamantas appears to be staying in his lane, allowing FDA staffers to complete their drug reviews without interference. Steven Grossman, president of policy and regulatory consulting firm HPS Group, previously predicted this may be the case. “As a lawyer, [Diamantas] may be more inclined to follow the agency’s traditional decision-making processes, which have served both the agency and its stakeholders well for many years,” Grossman said in the May 15 edition of FDA Matters: The Grossman FDA Report . “I would not expect him to be comfortable with the fiat decision-making that has predominated over the last 13 months. As a non-scientist, he may be more inclined to listen to the many deeply knowledgeable and expert FDA staff and advisers who are the backbone of the agency’s global leadership.” FDA Opinion: FDA Is Built on Predictability and Expertise, Not Norm-Breaking The FDA is becoming deeply compromised and increasingly at risk of being permanently transformed in ways contrary to its mission, history and culture. December 11, 2025 · 5 min read · Steven Grossman Read more But while Diamantas may appear to be a stabilizing force, his days as FDA commissioner are numbered—by law. Under the Federal Vacancies Reform Act, an acting official may generally serve for 210 days. Using May 12 as the start date, Diamantas could stay past the midterm elections this November but not much longer. So while some companies—and patient groups—might see a window of opportunity, what’s to reassure them and their stakeholders that the next permanent commissioner won’t just reverse the decisions made under Diamantas? After all, it’s happened before. In addition to the surprise decisions handed to uniQure and Replimune, Biohaven and Capricor Therapeutics also suffered from apparent FDA course reversals . In March 2024, the FDA had communicated to Biohaven regarding its application for its spinocerebellar ataxia drug that “a large and robust treatment effect would be needed to overcome the biases of an externally controlled trial,” something the company believed it had achieved—only to have the candidate rejected. Capricor’s cell therapy for Duchenne muscular dystrophy cardiomyopathy, meanwhile, was turned back in July. The decision “was unexpected given the trajectory of positive interactions” with the FDA, CEO Linda Marbán said during Capricor’s second quarter earnings call last year. FDA FDA Reversals Send UniQure, Biohaven, Capricor, More Into a ‘Tailspin’ Since July, several biotechs have been forced to pivot as previous agreements with the FDA around evidence required for approval were reversed, a phenomenon that, according to experts, could portend a more restrictive regulator. November 24, 2025 · 7 min read · Heather McKenzie Read more Regulatory consistency is critical, especially for biotech companies whose stock prices fluctuate wildly on mixed data, let alone a crippling rejection or regulatory delay. “If they’re making business decisions based on what FDA said, they need to be able to rely on that from administration to administration,” Holly Fernandez Lynch, associate professor of Medical Ethics and Health Policy at the University of Pennsylvania School of Medicine, told BioSpace of uniQure in March. However, she added that current FDA leadership is not necessarily obligated to follow previous guidance if they believe their predecessors were mistaken. So, what’s a biotech to do? .responsive-container { display: flex; flex-wrap: wrap; border: 1px solid #ededed; font-family: Helvetica, Arial, Sans-Serif; padding: 20px 20px 10px 20px; } .column-left { flex: 1; max-width: 45%; padding: 20px 20px 10px 20px; } .column-right { flex: 2; padding: 20px 20px 10px 20px; } @media (max-width: 768px) { .column-left, .column-right { max-width: 100%; flex: 100%; padding: 10px 0; } } Subscribe to ClinicaSpace! Clinical trial results, research news, the latest in cancer, cell and gene therapy hbspt.forms.create({ region: "na1", portalId: "4413123", formId: "674f4dc0-7371-4190-86cc-e1afd00b08ea", onFormSubmitted: function($form, data) { window.dataLayer = window.dataLayer || []; window.dataLayer.push({ 'event': 'GTMevent', 'event_name': 'newsletter_sign_up' }); } });