Selecta’s Methylmalonic Acidemia Gene Therapy Program Resumes

The FDA has lifted their clinical hold on Selecta Biosciences’ methylmalonic acidemia (MMA) gene therapy program.¹

The FDA had placed the program on clinical hold in November 2021 due to questions on chemistry, manufacturing, and controls (CMC) of the gene therapy candidate, SEL-302, which consists of the gene therapy MMA-01 in combination with Selecta’s ImmTOR nanoparticles which help suppress immune responses to auto-antigens and viral vectors.

“I am pleased to announce that on March 9th the FDA lifted the clinical hold on our SEL-302 gene therapy program to treat methylmalonic acidemia. We look forward to starting our phase 1 clinical trial expeditiously and to bring hope to those patients and families seeking a potentially durable and lifelong treatment for this terrible disease,” Carsten Brunn, PhD, president and chief executive officer, Selecta, said in a statement.¹

The clinical hold further delayed Selecta’s clinical trial plans, as it had previously disclosed in April 2021 that a manufacturing issue could potentially delay its application for human trials. Following this resolution of the clinical hold, the company said it plans to initiate the trial in the second half of 2022.²

READ MORE: Second Phenylketonuria Gene Therapy Study Put on Clinical Hold

While Selecta’s MMA program is back on track, LogicBio’s gene-editing phase 1/2 SUNRISE trial (NCT04581785) for the same indication has remained on hold since February 2022. The FDA placed the hold after the fourth patient dosed with 5 x 10¹³ vg/kg of the gene-editing therapy LB-001 experienced a treatment-related serious adverse event (AE) of thrombotic microangiopathy (TMA) in January 2022. Previously, the third patient dosed had experienced the same AE in November 2021. Both patients were the first to be dosed in the younger age group of 6 months to 2 years old.

The first 2 patients treated with the same dose of 5 x 10¹³ vg/kg of LB-001 in the older age group of 3 to 12 years have not experienced treatment-related serious AEs. The TMA experienced by the third patient has completely resolved as of December 2021. 

"Patient safety is our first priority. I would like to thank the patient and the patient's family for participating in our trial as well as the on-site team for the excellent care they are providing," Fred Chereau, president and chief executive officer, LogicBio, said in a statement.³ "We look forward to working closely with the FDA and the DSMB to determine the next steps for the trial and the program."

Selecta also provided other company updates, including an announcement of positive, proof-of-concept data in human trials with their other gene therapy candidate SEL-399. The company is evaluating the candidate, an empty vector capsid with ImmTOR nanoparticles, to potentially mitigate AAV antibodies in patients receiving gene therapies.¹

REFERENCES

1. Selecta Biosciences reports fourth quarter and full year 2021 financial results and provides business update. News release. Selecta Biosciences. March 10, 2022. https://ir.selectabio.com/news-releases/news-release-details/selecta-biosciences-reports-fourth-quarter-and-full-year-2021
2. Selecta Biosciences provides update on phase 1/2 clinical trial of SEL-302 for the treatment of methylmalonic acidemia-U.S. FDA has issued a clinical hold on phase 1/2 clinical trial of SEL-302 due to CMC related questions. News release. Selecta Biosciences. November 24, 2021. https://www.biospace.com/article/releases/selecta-biosciences-provides-update-on-phase-1-2-clinical-trial-of-sel-302-for-the-treatment-of-methylmalonic-acidemia-u-s-fda-has-issued-a-clinical-hold-on-phase-1-2-clinical-trial-of-sel-302-due-to-cmc-related-questions-/
3.LogicBio Therapeutics provides update on LB-001 clinical development program. News release. February, 022. https://www.prnewswire.com/news-releases/logicbio-therapeutics-provides-update-on-lb-001-clinical-development-program-301473512.html