Orforglipron

iStock, CoreDesignKEY Policy initiatives have come fast and furious at the FDA this year. While guidances on rare diseases and vaccines have consumed most of the ink, policy shifts aimed at improving FDA efficiencies and reshoring U.S. manufacturing also got some attention. Here, BioSpace rounds up more than a dozen initiatives relevant to the biopharma industry. From vaccines to rare diseases and the phasing out of animal testing requirements, it was a busy year for biopharma on the policy front as Health Secretary Robert F. Kennedy Jr. and his team at HHS made their mark on the FDA, CDC and National Institutes of Health. Many of the FDA’s 2025 guidances have focused on accelerating the path of cell and gene therapies to the market—particularly those intended for rare and ultrarare diseases. In a year where controversy is almost expected with every news announcement, the need for more and more-effective therapies for rare conditions may be the one area on which Americans of every political stripe can agree. Analysts and other FDA watchers who spoke with BioSpace see the momentum generated in this area in 2025 continuing into the new year. “I do think that, given what we’re seeing from FDA, rare orphan diseases as an area” of great interest for biopharma and investors will persist into 2026, Graig Suvannavejh, managing director of Equity Research at Mizuho Securities, told BioSpace . Married with reports that the FDA will soon begin requiring only one pivotal trial as opposed to the standard two, “this would make it seem ripe for rare orphan [diseases],” he added. Another key area of focus for the HHS under Kennedy—with his long history of antivaccine activism—has been in the vaccines space. On April 30, the Health department announced it would require all new vaccines be tested in placebo-controlled trials before they are approved, a “radical departure” from past practices, an HHS spokesperson told The Washington Post at the time. Earlier this month, Kennedy’s reformulated CDC Advisory Committee on Immunization Practices made another radical departure from the norm, voting to delay the hepatitis B vaccine from birth to two months of age for some infants. “Obviously [Kennedy is] driving a lot of this, from vaccine policy to staffing and everything like that,” Chad Landmon, Hatch-Waxman & Biologics chair at Polsinelli Law Firm, told BioSpace , “so I think it’ll be interesting to see how that continues, whether the same people continue in those roles.” BioSpace has compiled a review of our coverage of this year’s key policy initiatives. We will continue to update this tracker as we move into 2026 and see what comes next. _______________________________________________________________________ Randomized Trials To Be Required for CAR Ts December 8 Randomized, controlled clinical trials will be the FDA’s preferred approach to assessing CAR T cell therapies, Center for Biologics Evaluation and Research (CBER) director Vinay Prasad and three co-authors wrote in a Perspective piece in the Journal of the American Medical Association . Single-arm trials with no controls —the type on which the approvals for the seven currently marketed products were based—will no longer be sufficient. The FDA will also look at the therapy’s benefit in terms of patient survival or on time to the development of a particular event when considering approval, according to the authors. Prasad and colleagues noted in the piece that while the FDA is adjusting its processes to “exercise regulatory flexibilities, when necessary,” it also needs to “maintain the high evidentiary standards for approval.” FDA CAR-T Developers Will Need Randomized Trials as FDA Eyes Tighter Approval Requirements For traditional approval, CAR T therapies will need to establish superiority over current standard treatments, including already-approved CAR T products. December 9, 2025 · 2 min read · Tristan Manalac _______________________________________________________________________ FDA To Reduce Pivotal Trial Requirement From Two to One December 4 In possibly its biggest overarching pivot of 2025, the FDA is planning to require only one pivotal trial, as opposed to two, for companies seeking approval of a new drug. While not yet an official policy—the change was communicated by FDA Commissioner Marty Makary to STAT News in an interview—he told the publication it will be finalized in the next three to six months. “You can achieve the same statistical power with one trial as you would with two,” Makary told STAT . While analysts and other insiders positioned the proposed change as a major coup—biopharma consultant David Alderman in a LinkedIn post called it the “biggest jailbreak in biotech history”—other experts told STAT they were confused because the FDA already allows flexibility in situations where running two trials would be impractical or infeasible. _______________________________________________________________________ FDA Unveils Plausible Mechanism Pathway for Rare Diseases November 13 Makary and Prasad introduced the plausible mechanism approval pathway for rare diseases. Writing in The New England Journal of Medicine , Makary and Prasad said the new pathway would expedite treatments “for products where a randomized trial is not feasible.” In an interview with Fox News in April, Makary introduced the concept of a “conditional approval” pathway for treatments for rare diseases with extremely small patient populations. When the detailed pathway was announced seven months later, Makary and Prasad referenced Baby KJ , a patient with the ultrarare disease CPS1 deficiency whose condition was treated with a custom gene editing therapy. To qualify for the new plausible mechanism pathway, therapies must meet several conditions similar to KJ’s, including targeting known biological causes for a specific disease, and sponsors must produce post-marketing data to show real-world efficacy. FDA Makary’s ‘Conditional Approval’ Pathway for Rare Diseases Poses More Questions Than Answers While sparking excitement among biopharma companies focused on rare and ultrarare indications, experts say FDA Commissioner Marty Makary’s proposal is light on details and raises potential concerns about safety, access and liability. May 19, 2025 · 10 min read · Heather McKenzie _______________________________________________________________________ Guidance To Prevent Refusal-to-File (RTF) Letters October 23 The FDA released draft guidance to help biopharma companies understand what the agency considers to be a complete regulatory submission, and conversely, what will result in a refusal-to-file (RTF) letter. The guidance also explains the difference between filing issues that would result in an RTF and review issues that would result in a rejection. Recommendations include that a drugmaker not submit “materially incomplete or inadequately organized” applications, and that applications using a “single adequate and well-controlled clinical investigation” as the sole basis for approval will be RTF’d if the FDA and the applicant had previously agreed on the need for more than one such study. FDA FDA Provides Guidance To Prevent Returned Applications, Aid Patient-Focused Drug Development In three draft guidance documents, the FDA has laid out pointers to help companies craft better drug development programs and drug applications. October 24, 2025 · 2 min read · Tristan Manalac _______________________________________________________________________ Abbreviated NDAs Aim To Speed U.S. Generics October 3 Just over a week after its guidances for speeding the development of CGT therapies, the FDA on Oct. 3 introduced a new program for accelerating the generic drug industry in the U.S., both on the R&D and manufacturing sides. The agency’s new program includes a quicker review of abbreviated new drug applications —specific regulatory filings for generics—though the FDA did not say by how much it would accelerate review processes. Reviews for generic medicines generally take about 10 months. To qualify for that speedier review, companies must conduct their bioequivalence studies in the U.S. and “exclusively” source their active pharmaceutical ingredients from within the country as well. The finished dosage form must also be made locally. 2025 data showed that most generics are manufactured China and India, representing 22% and 44% of the global market, respectively. Manufacturing FDA Continues US Manufacturing Drive With Domestic Generics Pilot This latest FDA program aims to provide speedier reviews for generic drugmakers who produce their products in the U.S. October 6, 2025 · 2 min read · Tristan Manalac _______________________________________________________________________ FDA Seeks To Streamline Cell, Gene and Regenerative Therapies September 24 In a set of three separate draft recommendations, the FDA published new thinking on how to accelerate development of cell and gene therapies and regenerative medicines. These guidances covered a range of topics, including leveraging “innovative” study designs that use patients’ status prior to a trial as their own control. Other recommendations included using historical or real-world data as controls, allowing mid-trial modifications as studies generate data and deploying new mathematical frameworks to model progressions of a disease to chart the therapy’s efficacy. The agency also addressed diseases with small study populations, stating that early-stage trials could be enough to establish a product’s efficacy given “appropriate quality controls,” as well as post-marketing requirements for CGT products approved under accelerated pathways. FDA FDA Details Thinking for Streamlining Development of Cell, Gene, Regenerative Therapies Three draft recommendation documents published on Wednesday are intended to guide drug sponsors and accelerate the development of cell and gene therapies. September 25, 2025 · 2 min read · Tristan Manalac _______________________________________________________________________ FDA Cracks Down on “Deceptive” Drug Advertising September 9 The FDA on Sept. 9 announced it was sending approximately 100 cease-and-desist letters to pharmaceutical companies with what it called “deceptive advertisements.” The agency would also initiate rulemaking to close the “adequate provision” loophole, created in 1997, that has allowed pharma companies to advertise their drugs without fully disclosing risks, “fueling inappropriate drug use and eroding public trust,” according to the FDA’s statement. However, according to experts involved with writing the 1997 regulation who spoke with BioSpace , it was not a loophole. Instead, it was a deliberate and carefully crafted law that struck a happy medium between the demands for marketing new drugs and informing patients. FDA In New DTC Ad Crackdown, FDA Trying To Close a Loophole That Isn’t While the FDA is trumpeting this new initiative as “sweeping reforms” to the way drug companies can advertise, experts say the regulator is going after a problem that doesn’t exist. September 17, 2025 · 7 min read · Annalee Armstrong _______________________________________________________________________ FDA Unveils Rare Disease Evidence Principles September 4 The FDA’s Center for Biologics Evaluation and Research (CBER) and Center for Drug Evaluation and Research (CDER) on Sept. 4 jointly unveiled a new framework intended to streamline the approval of therapies for ultrarare diseases. The Rare Disease Evidence Principles (RDEP) will allow companies developing certain therapies to approval under an investigational new drug application using only a single-arm trial. This will apply to sponsors developing drugs for diseases that affect a “very small, rare disease population . . . generally less than 1,000 persons in the United States,” according to the FDA’s announcement . Qualifying conditions must also be linked to a known genetic defect and characterized by progressive functional deterioration leading to disability or death “in a relatively short period of time.” The targeted diseases should also lack “adequate” alternative therapies. Rare diseases Rare Disease Experts See Futility in FDA’s Proposed Framework The FDA’s proposed Rare Disease Evidence Principles review process is a starting point for getting rare disease therapies across the finish line, but industry leaders say there are more concrete steps the regulator could take to help patients. September 22, 2025 · 5 min read · Dan Samorodnitsky Rare diseases Saol To Pitch Ultrarare Disease Drug as “Poster Child” for RDEP Program Saol Therapeutics received a complete response letter for its pyruvate dehydrogenase complex deficiency treatment a week after the FDA unveiled its Rare Disease Evidence Principles program. On Dec. 18, in a Type A meeting, the biotech will attempt to convince the agency that its drug fits perfectly into the framework. December 9, 2025 · 2 min read · Heather McKenzie _______________________________________________________________________ FDA Pledges to Release CRLs in Real Time September 4 The FDA promised that, going forward, it would release new complete response letters (CRLs) to the public “ promptly after they are issued to sponsors .” In July, in a bid for “ radical transparency , ” the FDA released a bundle of more than 200 CRLs from a variety of drug and biological products applications submitted to the agency between 2020 and 2024. Big Pharmas like Eli Lilly and Regeneron were represented, as well as smaller biotechs like Sarepta. At the time, the FDA said the CRLs released were an “initial batch” without elaborating on its plans. Alongside the FDA’s September announcement, it released a second cache of heavily redacted CRLs, for products including Lykos Therapeutics’ MDMA-based therapy for posttraumatic stress disorder and Stealth BioTherapeutics’ elamipretide for Barth syndrome, approved later that month on a second try. As of December, the archive of CRLs has grown to 392. Complete response letters FDA Publishes Cache of Complete Response Letters in Bid for ‘Radical Transparency’ The trove of more than 200 letters is part of a pledge of transparency from the agency, with the intention to increase public insight into the reasons new drug and biologics applications got rejected. July 10, 2025 · 2 min read · Dan Samorodnitsky FDA Wall Street the Main Beneficiary of FDA’s Real-Time CRL Disclosures By publishing complete response letters as soon as they are issued to drug sponsors, the FDA is expanding transparency in a way that, while positioned as a public health measure, also grants investors greater visibility into regulatory decisions. Experts question whether this is the agency’s proper remit. September 29, 2025 · 6 min read · Ben Hargreaves _______________________________________________________________________ FDA Introduces PreCheck Program To Boost US Drug Manufacturing August 7 The FDA unveiled the PreCheck program with the intention of supporting biopharma companies as they build new facilities in the U.S. The PreCheck program provides manufacturers with more frequent FDA communication at critical development stages, including facility design, construction, and pre-production. A second Application Submission Phase centers around streamlining development of the Chemistry, Manufacturing, and Controls section of the application through pre-application meetings and early feedback. The program follows an executive order issued by President Donald Trump in May instructing the FDA to cut down on the 5–10 years it currently takes to build pharmaceutical manufacturing plants in the U.S. The EO also set the table for the FDA to implement surprise inspections on foreign plants, as opposed to the planned visits that are the current standard operating practice. “A scheduled visit is no inspection,” Makary said from the White House on May 5. The order will also see inspectors spend less time in the countries where the inspections take place, allowing them to “get in and out,” conducting more inspections with the same amount of resources, Makary said. The action is just one of many Trump has undertaken this year aimed at onshoring pharmaceutical manufacturing. Manufacturing Generic Drug and API Manufacturers Call for Onshoring Incentives Having seen Congress spend money to onshore semiconductor production, pharma groups are pushing for similar incentives for domestic drug manufacturing. November 4, 2025 · 4 min read · Nick Paul Taylor Manufacturing Pharmas Hope FDA PreCheck Can Help Avoid Facility-Related Drug Rejections Executives from Eli Lilly, Merck and other companies foresee the FDA’s new onshoring proposal being anything from a bureaucratic waste of time to a transformative program that will eliminate inspection-related complete response letters. October 28, 2025 · 4 min read · Nick Paul Taylor _______________________________________________________________________ Commissioner’s National Priority Voucher Program Introduced June 17 The FDA’s Commissioner’s National Priority Voucher (CNPV) program is intended to shorten review timelines for certain drugs from 10–12 months to 1–2 months. The initiative streamlines reviews by assembling a team-based review in a one-day “tumor board style” meeting, rather than shuttling applications sequentially through offices of the agency. For drugs to be awarded a CNPV, they must be “aligned with U.S. national priorities,” according to the FDA. Those priorities could include addressing a national health crisis, delivering “more innovative cures for the American people,” addressing an unmet public need or increasing domestic drug manufacturing. The FDA announced an initial batch of nine recipients in October, with an additional six awarded in November. A month later, the agency awarded its first CNPV approval of a generic antibiotic produced by USAntibiotic. Regulatory FDA Hands Out First Commissioner’s Priority Vouchers to Regeneron, Sanofi, Disc, Others The Commissioner’s National Priority Voucher awards companies that align with specific national priorities—such as boosting domestic manufacturing and lowering drug prices—with faster reviews and more frequent interactions with the FDA. October 17, 2025 · 2 min read · Tristan Manalac Regulatory Pressure On, Purpose Questioned as Second Round of FDA Priority Review Vouchers Revealed Priority voucher awardees and regulators could feel pressure to “meet the moment” as FDA watchers question the intent and feasibility of the Commissioner’s National Priority Voucher program. November 17, 2025 · 6 min read · Heather McKenzie Regulatory Wegovy, Casgevy Among Latest FDA Priority Review Voucher Recipients The FDA awards a second round of Commissioner’s National Priority vouchers to six larger biopharma companies. And this time, with the exception of Eli Lilly’s orforglipron, the vouchers are for drugs that are already on the market. November 6, 2025 · 3 min read · Dan Samorodnitsky _______________________________________________________________________ FDA Allows Drug Imports From Canada May 21 Drug pricing has been a top agenda item for the first year of President Trump’s second term. In May, Trump signed an executive order instructing U.S. health agencies to attempt to lower drug prices through whatever means are available to them. The FDA responded to that memo with a guidance that allowed states and Indigenous tribes to import prescription drugs from Canada, with the aim of lowering drug prices “without imposing additional risk to public health and safety.” In its announcement, the FDA said it anticipated meeting with states that expressed interest in the import program in the fall, though no such meetings have been announced. The Canadian government, for its part, made it clear that it would not export drugs to the U.S. “if that sale would cause or worsen a drug shortage in Canada,” according to a statement provided to BioSpace at the time. Drug pricing FDA Advances Drug Importation Plan as Canada Moves To Protect Its Supply Canada’s health agency says it has been “taking all necessary action safeguard the drug supply and ensure Canadians have access to the prescription drugs they need.” May 22, 2025 · 2 min read · Annalee Armstrong _______________________________________________________________________ HHS Requires Placebo-Controlled Trials for New Vaccines April 30 The Department of Health and Human Services announced it would require all new vaccines be tested in placebo-controlled trials before they are approved. While vaccines for new pathogens are already tested against placebo, new vaccines for other diseases are evaluated against existing interventions, largely for ethical reasons. The new policy “forces researchers to unethically withhold proven protection from some patients, all under the guise of ‘scientific rigor,’” Larry Bucshon, a cardiothoracic surgeon and former Congressman, wrote in an opinion article for STAT News . An HHS spokesperson told The Washington Post that the flu vaccine would be exempt from the new requirement as it “has been tried and tested for more than 80 years.” In a note to investors on May 1, analysts at Leerink Partners called the new policy “negative news for vaccine manufacturers,” including Merck, BioNTech and Moderna. Policy HHS To Require Placebo-Controlled Trials for All New Vaccines in ‘Radical Departure’ From Past The new policy, revealed by the Department of Health and Human Services on Wednesday, would make vaccines “less available and less affordable,” according to vaccine expert Paul Offit. It could also further complicate the picture for companies like Novavax. May 1, 2025 · 3 min read · Heather McKenzie _______________________________________________________________________ Restricting Pharma Representation on Adcomms April 17 One of FDA Commissioner Marty Makary’s earliest moves was to limit the ability of pharmaceutical company employees to serve on agency advisory committees . Even on committees where they are statutorily allowed to serve, the FDA said it would “prioritize and elevate” others on adcomms, particularly patients and caregivers. The agency noted that the change in policy did not preclude employees of regulated companies from attending or presenting to adcomms, and that exceptions could be made to allow their service on committees if they had unique expertise on a topic. This change was an early example of Makary’s efforts to “boost public trust” in the FDA, as the agency’s announcement put it. FDA FDA Moves To Restrict Industry Influence on Advisory Committees Industry representatives will still be allowed at these meetings, but they will no longer have a spot on the advisory committee. April 18, 2025 · 2 min read · Tristan Manalac _______________________________________________________________________ FDA To Begin Phasing Out Animal Testing April 10 In a move the FDA and U.S. government had been building toward for years, the agency announced plans to phase out its animal testing requirements for monoclonal antibodies and other drugs. The FDA plans to replace these animal models with “more effective, human-relevant methods,” such as AI-based computational models of toxicity, organ-on-a-chip systems and organoids. By leveraging nonanimal models, in addition to real-world human data, “We can get safer treatments to patients faster and more reliably, while also reducing R&D costs and drug prices,” Makary said in a prepared statement. “It is a win-win for public health and ethics.” Clinical Research FDA, NIH Accelerate Shift Away From Animal Research as Experts Warn of Limitations The FDA and NIH recently announced plans to phase out animal testing requirements for some therapies. While organoid and AI providers celebrate, scientists warn that questions over safety, applicability and implementation remain. May 19, 2025 · 6 min read · Natalia Mesa FDA New Approach Methodologies: Redefining Animal Testing Alternatives In this episode of Denatured, Jennifer C. Smith-Parker speaks to Stacey Adam, PhD, Vice President of Science Partnerships at the Foundation for the National Institutes of Health and Patrick Smith, Senior Vice President, Translational Science at Certara, to discuss the latest regulatory news and the future for new approach methologies (NAMs) development. December 4, 2025 · 1 min read · BioSpace Insights

Today, a brief rundown of news from Novo Nordisk and Merck & Co., as well as updates from Pfizer, Camp4 Therapeutics and Chai Discovery that you may have missed.Novo Nordisk on Thursday said it filed an application for U.S. approval of CagriSema, its weekly injectable for obesity. Earlier this year, the Danish drugmaker disappointed investors when the drug, a combination of an amylin-targeting medicine and semaglutide, missed the mark in a closely watched late-stage study. Still, its application is based on data from that trial, which found that patients shed an average of 23% of their body weight over 68 weeks, as well as a secondary study. Novo hopes to position CagriSema as a follow-up to the success of Wegovy, and to take the edge off the threat of its competitor Eli Lilly, which recently submitted an application for approval of its oral GLP-1 orforglipron. It would be the first amylin-targeting and GLP-1 combination on the market if approved. Gwendolyn WuCamp4 Therapeutics, an RNA-targeting biotechnology company, has inked a deal with GSK worth as much as $440 million to make medicines for neurodegenerative and kidney diseases. In a Thursday announcement, Camp4 said GSK would hand over $17.5 million in upfront costs, and could pay tiered royalties if any of the programs that emerge from the collaboration are commercialized. The partnership is focused on antisense oligonucleotide drugs that boost gene expression, which could be beneficial in genetic disorders caused by loss of function. Camp4 also announced the pricing of a $30 million public stock offering on Thursday. Gwendolyn WuA San Francisco-based AI drugmaker, Chai Discovery, has raised $130 million in a Series B financing to support its ambitions of speeding up the drugmaking process. The company claims its technology can predict how biochemical molecules interact with one another and find new ways to pursue hard-to-drug targets. Its investor syndicate included Oak HC/FT and General Catalyst, which co-led the round, as well as others such as Thrive Capital, OpenAI and Yosemite. Chai raised its $70 million Series A funding just four months ago. Gwendolyn WuA combination of Merck & Co.s immunotherapy Keytruda and the Pfizer/Astellas antibody-drug conjugate Padcev succeeded in another bladder cancer study, helping people who are otherwise eligible for chemotherapy live longer than those who got chemo, the companies said Wednesday. Trial enrollees had muscle-invasive bladder cancer that hadnt spread outside the bladder, and were undergoing surgery with curative intent. Participants were randomized to receive either Keytruda and Padcev before and after surgery or platinum-based chemo before surgery. Trial investigators then measured event-free survival, overall survival and remission rates. Beyond stating that the Keytruda-Padcev combination had a statistically significant and clinically meaningful benefit on those three measures, the companies didnt release specifics but said they will disclose data at a coming medical meeting. The combination has also improved survival for those who cant receive chemotherapy as well as those whose disease spread beyond the bladder. Jonathan GardnerAdaptive Biotechnologies said Monday it has signed two non-exclusive licenses with Pfizer to use its T cell receptor technology for discovery of potential therapeutic targets in people with rheumatoid arthritis. Under one deal, Adaptive will lead target discovery activities and Pfizer will be responsible for development and commercialization of any drugs that emerge from the research. Adaptive said the deal includes an unspecified upfront payment and will be eligible for additional payments based on achievement of specific data delivery, development, regulatory and commercial goals, all worth a potential total of $890 million. The second agreement will give Pfizer access to Adaptives T cell receptor-antigen dataset to accelerate its own research and drug discovery. That deal involves an unstated upfront payment and annual licensing fees. Jonathan Gardner '