Sarepta’s Lack of Confirmatory Trials Draws FDA Criticism

A new document that has emerged in the internal FDA debate over the controversial December approval of Sarepta Therapeutics’ Vyondys 53 makes clear the agency also has significant concerns about Sarepta’s sister drug for DMD, Exondys 51, which was approved in 2016.

Sarepta only this month launched a confirmatory trial on Exondys 51 (eteplirsen), nearly four years after it was supposed to have started the trial. The criticism came to light last week when the FDA released its complete response letter (CRL) on Sarepta’s Vyondys 53 (golodirsen). That drug was approved in December under the accelerated approval pathway after its earlier rejection in August, when the CRL was first sent to Sarepta.

Sarepta was supposed to have initiated the eteplirsen confirmatory trial in 2016. Sarepta says the trial was delayed because it needed to do another study of the drug at a “significantly higher dose” to determine the proper dose for the confirmatory trial. “That trial is complete and the (confirmatory trial) is well underway,” Tracy Sorrentino, a Sarepta spokesperson told CenterWatch Weekly. Sarepta is on track to complete that trial by October 2024.

The Vyondys CRL was written by Ellis Unger, director of FDA’s Office of Drug Evaluation I, who opposed the accelerated approval of eteplirsen. “Please understand that your failure to initiate eteplirsen’s confirmatory study with due diligence is very concerning to FDA and is of concern to the public,” he wrote.

The agency is also insisting on a confirmatory trial for golodirsen. That trial, which is supposed to be completed by May 2023, is well underway, Sarepta says, was 75 percent enrolled at the time of the drug’s approval and will be completed on time.

When Sarepta was first notified of the rejection of golodirsen, it appealed to the FDA for a formal dispute resolution. In November, director of FDA’s Office of New Drugs Peter Stein granted that appeal. While Stein concluded that golodirsen has clinically meaningful benefits, he asked Sarepta to provide written commitment “that they will voluntarily withdraw golodirsen from the market” if a confirmatory study fails to support a clinical benefit.

To read the CRL, click here: https://bit.ly/2viWyK9.

Blood Cancer Trials May Use Minimal Residual Disease Measures as Endpoints, Guidance Says

Trials for hematologic malignancies can use measures of minimal residual disease (MRD) as a biomarker, according to a final guidance issued by the FDA that specifies the types and uses of measures the agency will accept.

Studies conducted under an Investigational New Drug (IND) application may use MRD as an efficacy biomarker to predict a specific clinical outcome and establish a surrogate endpoint, the guidance says.

To ensure MRD can be applied as an efficacy biomarker in a variety of trials, it should be tested against multiple drugs with varying mechanisms of action, the guidance says.

Trials that propose to use an MRD biomarker that has not been approved by the FDA and that include a device considered by the agency to be high risk may require an investigational device exemption from the agency in addition to an IND.

The final guidance is unchanged in substance from the draft issued in 2018, which drew comments from 14 pharmaceutical companies and other organizations, most of which requested clarification of specific points rather than changes in content.

Read the final guidance here: https://bit.ly/3aLpyuz.

FDA to Issue New Guidance on Civil Money Penalties for Nonreporting of Trial Results

The FDA says a new guidance on compliance with ClinicalTrials.gov reporting requirements is in the works and will clarify how the agency plans to penalize sponsors that don’t report trial results within a year of completion.

FDA regulations give the agency the authority to levy fines of more than $10,000 per day to trial sponsors who do not report their trial results. The agency has not enforced that rule since it was issued in 2018 and says it will not impose fines until the new guidance is issued.

A recent study showed only 66 percent of trials have complied with the federal mandate to report results within one year of completion (CenterWatch Weekly, Nov. 15, 2019).

UK Aims to Establish Itself as Leader in Cell and Gene Clinical Trials

The number of cell and gene therapy clinical trials in the UK increased by 45 percent from 2018 to 2019, according to a new study.

Currently, the UK has 127 ongoing cell and gene therapy trials, which represents approximately 12 percent of ongoing global trials in this area, according to Cell and Gene Therapy Catapult’s (CGTC) 2019 report on the industry.

CGTC, a UK-based clinical trial services company, says that on average, the number of trials in this space has been growing by 25 percent each year since 2013. A majority of these trials in the UK – 77 percent – are industry supported, establishing the UK as a leader in this emerging field.

EU Court of Justice Sides with EMA in Transparency Case Against Merck and PTC Therapeutics

The European Court of Justice has ruled in favor of the European Medicines Agency’s (EMA) decision to release clinical study data from trials led by Merck and PTC Therapeutics.

Merck and PTC Therapeutics had filed lawsuits against the EMA, arguing that the release of that data may place their commercial properties at risk.

The Court of Justice announced, however, that the release of the clinical trial data and toxicology reports does not fall within the exception relating to the protection of commercial interests.

Additionally, the Court of Justice has denied pleas by Merck and PTC that the released reports were protected by a presumption of confidentiality. According to the court, the EMA is not obliged to apply a presumption of confidentiality on clinical study reports. Merck and PTC were also ordered to pay legal fees the EMA has incurred.

Notable Labs Tests Predictive Value of AI Platform in Patients with Blood Cancers

Notable Labs has launched an observational trial to test the predictive value of the firm’s artificial intelligence (AI) patient-matching platform.

The ANSWer study will follow 1,000 patients from the U.S. and Canada with different types of blood cancers for up to one year while they are treated with standard-of-care therapies to create a tumor registry that includes patient outcomes.

Notable’s phenotypic and AI platform will also be tested against multiple already-collected patient samples to assess the tool’s predictive accuracy. The platform will also search for patterns useful in the development of new treatments.

WCG Acquires Statistics Collaborative

WCG Clinical last week announced the acquisition of Washington, D.C.-based Statistics Collaborative, a biostatistical consultancy specializing in pharmaceutical and biologics clinical trials.

The company’s primary focus is late-stage clinical trials, where it contributes to trial design, reporting for data monitoring committees, data analysis and consultation for FDA presentations.

Mayo Clinic and Helix Team Up to Build Genomic Database of 100,000 Participants

Mayo Clinic and genomics company Helix are collaborating on a project to sequence 100,000 consented Mayo Clinic patients to build a genomic database for use in clinical trials.

Trial participants and their Mayo Clinic provider will receive results of the sequencing, which will initially screen for three frequently unrecognized hereditary conditions, including familial hypercholesterolemia, hereditary breast and ovarian cancer, and Lynch syndrome.