The PDUFA data has been set for March 18, 2024.
Orchard Therapeutics’ biologics license application (BLA) for atidarsagene autotemcel (arsa-cel, also referred to as OTL-200 and approved as Libmeldy in the European Union, UK, Iceland, Liechtenstein, and Norway), a gene-edited cell therapy being evaluated for the treatment of metachromatic leukodystrophy (MLD), has been accepted by the FDA with priority review.1,2 The Prescription Drug User Fee Act (PDUFA) date is set for March 18, 2024.
“Today is another significant step forward for patients and families in the US impacted by this devastating and cruel disease who for too long have dealt with the unimaginable burden of going through the diagnostic odyssey, being told there were no treatments beyond supportive care, and then having to watch their child slip away,” Bobby Gaspar, MD, PhD, the cofounder and chief executive officer of Orchard Therapeutics, said in a statement.1 “We look forward to collaborating with the FDA throughout the review and evaluation of our application. Due to the nature of the disease and the urgency to treat children affected by MLD, we are working diligently in parallel to prepare for a potential launch in 2024 and ensure OTL-200 will be available to patients in the US as quickly as possible.”
The company recently presented updated data from an integrated analysis of 39 patients treated with arsa-cel at the Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium in Jerusalem, Israel, in August; the data included 30 patients treated across 2 clinical trials (NCT01560182; NCT03392987) and 9 patients treated in expanded access frameworks who had follow-up times ranging from 0.64 years to 12.19 years (median, 6.76).2 The integrated analysis included measurement of the interval of time from patients’ birth to their first losses of locomotion or sitting without support or their deaths, an end point dubbed severe motor impairment-free survival (sMFS) that the FDA deemed clinically meaningful in discussions with Orchard Therapeutics. The company reported that compared to disease natural history data from 49 untreated patients, patients treated with arsa-cel achieved clinically meaningful improvements in sMFS in in the study’s subgroups for presymptomatic (PS) late-infantile (LI) (P < .001), PS early-juvenile (EJ) (P = .042), and early symptomatic EJ MLD (P < .001).
“MLD is a devastating and ultimately fatal disease for which there are no alternative treatment options beyond supportive care,” Leslie Meltzer, PhD, the chief medical officer of Orchard Therapeutics, said in an August 2023 statement.2 “These data, which now encompass more than a cumulative 250 years of patient experience, continue to show sustained preservation of cognitive function and motor development in most patients compared to disease natural history consistent with previously published results. Moreover, results from the updated integrated analysis presented at SSIEM are key components of the clinical package in the OTL-200 BLA we recently submitted to the FDA.”
Orchard originally submitted the BLA to the FDA on August 3, 2023.3 The BLA specifically pertains to the treatment of early-onset MLD. In the European Union, arsa-cel is approved for an indication covering its use in patients with MLD who have biallelic mutations in the ARSA gene that have caused a decrease in ARSA enzyme activity; patients must be children with the LI or EJ forms without clinical manifestations or patients with the EJ form who have early clinical manifestations and retrain the ability to walk independently and have not yet shown cognitive decline.1