After Vanda Pharmaceuticals’ phase 3 miss and FDA rejection for its stomach disorder candidate, CEO Mihael Polymeropoulos, M.D., is calling out the regulatory agency for a “disturbing pattern of conduct” that “harms the American public.”
In a searing letter penned to current FDA Commissioner Robert Califf, M.D., Polymeropoulos addresses the rejection Vanda received in September 2024, deeming the agency’s review process as “faulty,” according to the Jan. 8 letter (PDF).
The biotech had requested approval for its NK-1R antagonist tradipitant in gastroparesis, with Polymeropoulos claiming at the time that the complete response letter (CRL) generally disregarded the evidence.
In a late-stage study (PDF), tradipitant was no better than placebo at reducing the severity of nausea across 12 weeks of treatment, but Vanda identified a baseline imbalance of rescue medication use between the treatment arms and some poor compliance with the study drug as a potential cause for the miss. When excluding patients that Vanda deemed to be confounders, the company said the study hit its primary endpoint.
Now, the CEO is accusing the FDA of skirting public scrutiny for its decisions, something he says could threaten both public health and the agency’s credibility.
“In an interview last year you stated that you would not overrule decisions made by civil servants at the agency except in certain cases of ‘corruption’ or ‘temporary insanity’ of the decision maker,” Polymeropoulos wrote, referring to April 2023 MedPage interview with Califf. “Neither the public nor regulated entities like Vanda are able to determine what instances of ‘corruption’ or ‘temporary insanity’ would in your view merit overruling lower-level FDA employee decisions. This opacity in decisionmaking and oversight has allowed a culture of obfuscation and closemindedness to fester at FDA.”
Last fall, after Vanda received the CRL, Polymeropoulos said he wrote a letter to the FDA’s director of immunology and inflammation Nikolay Nikolov, M.D., regarding the agency’s alleged “sheer disregard for the facts, evidence, and basic scientific principles.” Now, the Vanda CEO claims that Nikolov hasn’t yet acknowledged or responded to his letter.
The CEO writes that the lack of response is “unacceptable” and “stems from the seriously misguided nature of your position that you will not overrule decisions made by civil servants at the agency except in extreme situations such as ‘corruption’ or ‘temporary insanity’ of the decision maker,” according to the Jan. 8 release.
Polymeropoulos also takes issue with certain advisory committee practices, writing that the FDA denied Vanda’s request to hold an adcomm for tradipitant, a process in which experts and members of the public can share their thoughts on new drug applications.
At the end of the letter, the CEO acknowledges that Califf may be leaving the FDA soon under the upcoming Trump administration, but he still hopes that the commissioner will consider his thoughts.
Polymeropoulos’ criticism of the FDA is not new: he previously voiced frustrations with the approval process in the run-up to the PDUFA date. In 2020, the biotech took the agency to court over a partial clinical hold for a tradipitant trial, a suit that ultimately landed in favor of the FDA.
Vanda’ has been working to snag a tradipitant approval for years after licensing the molecule from Eli Lilly in 2012 and attempting to establish the molecule in eczema—efforts that ended up falling short.
In May 2024, the biotech said it planned on filing for approval in the prevention of vomiting in motion sickness by the end of the year.