Court Rules More Trial Data Must Be Posted On ClinicalTrials.gov

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Plaintiff Peter Lurie, former US FDA associate commissioner, expects results of hundreds of clinical trials of approved drugs will become available under ruling against HHS; co-plaintiff sought eteplirsen study data.

The results of potentially hundreds of clinical trials of approved drugs and medical devices will have to be published on the ClinicalTrials.gov website in the wake of a US federal court ruling.

The court found that the US Department of Human Services erred in concluding that a 2007 law requiring clinical trial sponsors to post these trial results did not apply before it issued an implementing regulation a decade later.

In a 24 February memorandum and order, Judge Naomi Reice Buchwald, of the US District Court for the Southern District of New York, set aside HHS’s interpretation of its rule and ordered the department to require trial sponsors to submit basic results of clinical trials conducted in the 10 years between the statute’s enactment and HHS’s implementing regulation.

The suit was brought against HHS, the US Food and Drug Administration and the National Institutes of Health by the Yale Media Freedom and Information Access (MFIA) Clinic and the New York University Technology Law & Policy Clinic on behalf of Charles Seife and Peter Lurie in December 2018. Seife, a journalist and professor at NYU, had sought the results of a study of Sarepta Therapeutics Inc.‘s (NASDAQ: SRPT). eteplirsen, which were not included on ClinicalTrials.gov. Lurie is president of the Center for Science in the Public Interest (CSPI) and former associate commissioner for Public Health Strategy and Analysis at FDA, who claimed the absence of trial data hampered his research into the integrity of the clinical trial research enterprise.

Lurie said the 10 years of trial results now required to be posted involve products that were ultimately approved and are on the market.

“We think there are hundreds of them,” Lurie said, given that the FDA approves about 30 drugs per year and at least two trials were conducted for most of them.

While they represent a small subset of all the trials published on ClinicalTrials.gov, they are “in some respect the most important,” he said. “They were pivotal in the generation of evidence that led” to a product’s approval and exposure of Americans to it.

It is uncertain whether the government will appeal the ruling. An FDA press officer said the agency does not comment on possible, pending or ongoing litigation.

HHS Rule Conflicts With Statute’s Text

The FDA Modernization Act, enacted into law in 1997, required the secretary of HHS, acting through the director of NIH, to establish and operate a data bank of information on clinical trials for drugs for serious or life-threatening diseases or conditions. HHS and NIH created ClinicalTrials.gov, a publicly accessible online clinical trial database, in 2000. The FDA Amendments Act (FDAAA) of 2007 defined a set of “applicable clinical trials” for which trial sponsors or principle investigators must submit clinical trial results for inclusion on ClinicalTrials.gov.

The statute distinguishes between basic results and expanded results. It requires that ClinicalTrials.gov include basic results for any applicable clinical trial (ACT) of a drug or device that is approved.

In September 2016, HHS issued a regulation to implement FDAAA, which became effective on 18 January, 2017. In the preamble to the rule, HHS interpreted “is approved” so that an applicable clinical trial completed after the enactment of the FDAAA but before the final rule became effective did not need to submit the basic results if the trial studied a product that was approved after the trial’s completion. The court referred to these as pre-rule, pre-approval ACTs.

Judge Buchwald rejected the defendants’ argument that requiring parties to submit basic results for nearly a decade of pre-approval ACTs, which HHS had not previously required them to do, would apply HHS’ rule retroactively.

“But responsible parties knew since the FDAA’s enactment in 2007 that the statute required them to submit basic results for each ACT of a product that is approved,” she stated. “It was only when HHS promulgated the final rule nearly 10 years after the FDAAA’s enactment and almost six years after the statutory deadline for doing so, and included in its preamble an interpretation of it that was contrary to the text of the FDAAA, that HHS definitively told responsible parties that they were not required to submit basic results for pre-Rule, pre-approval ACTs.”

As for how HHS might require responsible parties to submit this missing data, Lurie said it could identify newly approved products in the window period and determine if trials for them were posted on the ClinicalTrials.gov website. If they are not there, the agency could send sponsors a note requesting them to submit the data.

Searching For Eteplirsen Study

The court cites Seife’s efforts to obtain information about a clinical trial of Exondys 51 (eteplirsen), Study 202. It says Seife began researching the drug in 2016 to evaluate the scientific soundness of the FDA’s decision to approve eteplirsen for treatment of Duchene muscular disease. Center for Drug Evaluation and Research Director Janet Woodcock granted approval of the drug in September 2016 despite opposition from other agency personnel.

The court says Study 202, which evaluated eteplirsen’s effectiveness, was retracted from publication due to its flaws and was absent from ClinicalTrials.gov. The court notes that the FDA published the basic results of the study on ClinicalTrials.gov on 10 July, 2019, one month after Seife submitted a declaration regarding his eteplirsen research in support of his claim to have standing in the suit.

The ruling notes that Seife also sought access to basic results of a clinical trial of Paratek Pharmaceuticals Inc.‘s (NASDAQ: PRTK) omadacycline, which was never completed and was terminated by Paratek in 2012. FDA approved the drug, Nuzyra, in 2018 for treatment of certain bacterial infections.

FDA, NIH Do Not Report Noncompliance

The court denied plaintiffs’ request for a ruling that NIH’s failure to post notices on ClinicalTrials.gov of a party’s noncompliance with requirements to register and report clinical trials is unlawful. Granting defendants’ motion for summary judgment on this claim, the court said NIH’s obligation to post a noncompliance notice is contingent on FDA issuing a notice of noncompliance. It says FDA’s failure to do so is not subject to judicial review and therefore NIH’s inaction cannot be subject to judicial review.

The court noted that FDA has yet to issue a noncompliance notice and NIH also has not posted a public notice of noncompliance or created a search function for such notices on ClinicalTrials.gov.

This article was first published on 26 February 2020 in The Pink Sheet.

Image: iStock/Artur

Brenda Sandburg is a senior writer who covers legal issues and FDA regulatory policy, with a particular focus on patents, biosimilars, and government investigations. She can be reached at Brenda.Sandburg@informa.com Follow @brendasandburg

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