The Food and Drug Administration (FDA) has extended the review periods for 2 investigational products: sparsentan and tofersen.

Sparsentan is a dual endothelin angiotensin receptor antagonist under review for the treatment of immunoglobulin A (IgA) nephropathy. The rare disease is characterized by the accumulation of IgA in the kidneys, which causes cellular changes within the glomeruli and damages the glomerular filtration barrier.

The FDA had granted Priority Review to the New Drug Application (NDA) for sparsentan in May 2022 based on data from the phase 3 PROTECT study (ClinicalTrials.gov Identifier: NCT03762850); the original Prescription Drug User Fee Act (PDUFA) target action date had been set for November 17, 2022. The date has now been extended by 3 months as the FDA has requested Travere Therapeutics update the proposed Risk Evaluation Mitigation Strategy (REMS) to include liver monitoring consistent with other approved products in the endothelin receptor antagonist class.

“While this request for additional monitoring within the REMS came unexpectedly, the strength of the clinical data supporting the profile of sparsentan and our confidence in the potential for sparsentan to be approved as a new therapy for IgA nephropathy remain unchanged,” said Eric Dube, PhD, president and chief executive officer of Travere Therapeutics.

The PDUFA date for tofersen has also been extended by 3 months to April 25, 2023. Tofersen is an antisense medicine being reviewed for the treatment of superoxide dismutase 1 amyotrophic lateral sclerosis (SOD1-ALS). The treatment reduces the synthesis of SOD1 protein production by binding to SOD1 mRNA, allowing for its degradation by RNase-H.

The NDA for tofersen, which received Priority Review, was supported by data from the phase 3 VALOR study (ClinicalTrials.gov Identifier: NCT02623699) and the ongoing open label extension phase of the trial (ClinicalTrials.gov Identifier: NCT03070119). According to Biogen, the extension was necessary as the responses to information requests given to the FDA were considered a major amendment to the application.

“We are committed to providing any details the agency needs to complete the review of tofersen,” said Priya Singhal, MD, MPH, Head of Global Safety and Regulatory Sciences and Interim Head of R&D at Biogen. “As the review continues, Biogen will maintain the early access program for tofersen.”

Tofersen is also being evaluated in the phase 3 ATLAS trial (ClinicalTrials.gov Identifier: NCT04856982) in clinically presymptomatic adults with a SOD1 genetic mutation and biomarker evidence of disease activity.

References

  1. Travere Therapeutics provides regulatory update on its sparsentan program for IgA nephropathy. News release. October 13, 2022. Accessed October 17, 2022. https://ir.travere.com/news-releases/news-release-details/travere-therapeutics-provides-regulatory-update-its-sparsentan
  2. Biogen announces FDA’s 3-month extension review period for the New Drug Application for tofersen. News release. Accessed October 17, 2022. https://www.globenewswire.com/news-release/2022/10/17/2535365/0/en/Biogen-Announces-FDA-s-3-Month-Extension-of-Review-Period-for-the-New-Drug-Application-for-Tofersen.html