Seikagaku Corp.

iStock, Radachynskyi In a year that saw advisory committees placed under a particularly bright microscope at the FDA, the agency held fewer meetings than usual and agreed with its advisors only 57% of the time, Jefferies reported. The FDA went against the recommendation of its advisory committees on 3 of 7 occasions in 2025, Jefferies reported in a note to investors on Saturday—a considerable departure from recent years. Those three decisions—an approval for UroGen Pharma’s Zusduri after a negative adcomm vote, a rejection for Seikagaku Corporation’s SI-6603 after a positive adcomm and a closely-watched approval for GSK’s Blenrep after a negative adcomm vote —represent 43% of all 2025 adcomms, according to Jefferies, compared with a 16% discordance rate between 2020 and 2024. That there were only seven advisory committee meetings—and that all seven occurred earlier in the year—could also be a bellwether of things to come at the FDA in terms of how decisions on new drugs and indication expansions are made. There were an average of 12 adcomms between 2021 and 2024, but only five in the COVID-19-impacted 2020 Adcomms were an early target of Health Secretary Robert F. Kennedy Jr. and FDA Commissioner Marty Makary when they took office early in 2025. On April 17, Makary announced that the FDA would limit pharmaceutical company employees from serving as members on its independent advisory committees in a move he said would help “restore impeccable integrity” to the drug review process and minimize or eliminate “potential conflicts of interest at the agency.” This followed remarks made by Kennedy during a tour of the FDA campus where he blasted the agency and its staff, accusing them of being a “sock puppet” to the pharma industry. Then, in September, then-Center for Drug Evaluation and Research director George Tidmarsh said he was considering a move to “abandon” the use of advisory committee meetings for specific drugs, according to reporting by KFF Health News . “I don’t think they’re needed,” Tidmarsh said at a meeting of healthcare product developers and to an advocacy group, according to KFF , adding that the reviews are redundant and require “a tremendous amount of work for the company and for the FDA.” While Tidmarsh appeared to walk those comments back in an interview with Endpoints News —and resigned from his post in early November amid a probe into his “personal conduct” at the agency—Jefferies in its Jan. 3 report flagged “an absence of new AdComs” since its August 2025 update. The analysts said this largely reflects “FDA’s decision in Sep 2025 to phase out AdComs for individual drug applications, which were viewed as time-consuming.” One adcomm meeting that did go ahead last year, an Oncologic Drugs Advisory Committee (ODAC) session that convened in May to discuss four separate drug applications—was apparently thrown into “absolute chaos” in part by a hiring freeze preventing the recruitment of temporary members with expertise pertaining to the specific indications, according to an agency insider who spoke with BioSpace . When it came to advisory committee meetings, the source said in May, the FDA was operating with a “fake it till you make it” mentality. Apart from an apparent late-year pause in advisory committee meetings, the FDA experimented with another feedback format last year: expert panels . The agency held two such panels this summer, one focused on the use of selective serotonin reuptake inhibitor (SSRIs) during pregnancy, the other on menopause and hormone replacement therapy. The panels drew criticism from medical experts and FDA watchers for being one-sided. Diana Zuckerman, president of the nonprofit National Center for Health Research, was struck by the lack of nuance presented during these panels. “It seemed they didn’t want any real difference of opinion,” she told BioSpace in September.

Despite some safety concerns, an FDA advisory committee on Friday voted 8 to 4 in favor of Japan-based Seikagaku’s condoliase injection for the treatment of radicular leg pain associated with lumbar disc herniation in adults. Much of the discussion centered on one of Seikagaku’s three clinical trials presented before the committee that failed on its primary endpoint and several secondary endpoints. Overall, the members of the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee said the negative study should be weighed appropriately by the agency, and they raised short and long-term safety questions about the injection. Committee chair Brian Bateman of Stanford University School of Medicine, who voted against the injection, cautioned that the population in the negative, US-based study “might reflect the population that would ultimately use it.” He also noted several safety concerns, including that the drug has to be used in a setting that can treat anaphylaxis, and that those receiving the drug can be at risk of severe cutaneous adverse reactions (SCARs). Committee panelist Steven Schiff, professor of neurosurgery at Yale University, who voted in favor of condoliase, also raised concerns about larger numbers of people accessing it. “I could envision in the next years, a million people might get this therapy,” Schiff said, and if the prevalence of SCARs is about one in 1,000, as Seikagaku estimates, a few hundred cases of these life-threatening reactions in the US “might cause the FDA to think twice” about the approval. Michael Sprintz of Ethos Behavioral Health Group in Houston voted in favor of the injection but said he hopes the label will be appropriately narrow and ensure that those who receive it fail on the more commonly used therapies. Lumbar disc herniation can cause lower back or leg pain, but is typically resolved with existing medicines. About 20% to 50% of those in pain progress to surgery, Seikagaku said Friday. The company has presented condoliase as a less invasive alternative to surgery. About 29,000 patients have been treated with condoliase, first approved in Japan in 2018, the company said. Two of the studies were based in the US, but only one of those was positive. One key way that the two trials differed was that in the positive trial, the company used MRIs to find evidence of nerve impingement before administering the drug. But some of the panelists questioned if the MRI scans were the primary reason for the differences between the failed and positive studies. Schiff noted that the two US-based studies had very different populations and indications. And while he’s not surprised by the one failed study, he did ask: “How do you translate the success of the second study given the very rigorous inclusion and exclusion criteria? How does that get translated into approval?” DJ Kennedy of the Vanderbilt University Medical Center, who voted in favor of the drug, also said that the application of condoliase in the real world will likely be more similar to what occurred in the negative study, “unless there’s significant efforts to make that not the case.” But the experience of using the drug in Japan could be informative to the FDA in making its approval decision. ‘The longer term studies out of Japan are reassuring, maybe not completely sufficient, but they are reassuring,” Kennedy said.

Japan-based Seikagaku will face an FDA advisory committee on Friday, with the agency raising concerns ahead of the meeting regarding the efficacy of its condoliase injection for the treatment of radicular leg pain associated with lumbar disc herniation in adults. Ahead of the meeting of the Anesthetic and Analgesic Drug Products Advisory Committee, the FDA notes that one of the clinical trials failed on its primary endpoint. Overall, the agency sounded positive on an approval, noting in briefing documents released Wednesday that “the negative study may inform the benefit-risk assessment for specific populations who may be considered for treatment with condoliase if the product is approved.” One of the three clinical trials evaluated by the FDA did not meet its primary efficacy endpoint (change in worst leg pain from baseline to week 13), nor did it meet either of its two key secondary endpoints, including a pain outcome assessment after a year. The change from worst leg pain from baseline to week 52 slightly favored the control in the failed study, FDA said, but the difference was not statistically significant. The agency also noted that the study that failed likely did so because herniation resulting in symptomatic nerve impingement was not present in most of the patients enrolled, and that’s what the injection targets. The agency said that Seikagaku “performed a detailed analysis to explain the negative U.S. findings despite the positive findings in Study 1031 in Japan.” The company highlighted two key issues: 1) A majority of patients in the failed trial did not have definitive impingement of the nerve root by the disc herniation on an MRI. 2) Baseline back pain was significantly higher in the US study compared to the study in Japan. Two other Phase 3 clinical trials were positive, although one was conducted exclusively in Japan. And in both trials, nerve impingement conducive to condoliase treatment was confirmed by imaging, FDA said. Friday’s committee will have an up-or-down vote on the injection, with the question presented as, “Do the benefits of condoliase injection for treatment of radicular leg pain associated with confirmed nerve root impingement caused by lumbar disc herniation in adults with radicular leg pain outweigh the risks?” Seikagaku, which also markets an intra-articular injection for the treatment of knee osteoarthritis in the US, calls its condoliase injection an improvement on the current treatment landscape, because it does not require general anesthesia and is “less invasive to the patient than surgical treatment.”