Orchard Therapeutics is pulling its EMA-approved gene therapy Strimvelis off the shelves while it investigates a potential link between the drug and a case of lymphoid T-cell leukemia.
The biotech $ORTX said it was notified of the adverse event a few days ago — just months after it slashed 25% of its workforce in an attempt to stray away from rare diseases like “bubble boy syndrome,” the one Strimvelis is approved for. The patient was treated under a compassionate use program in 2016, and is now being treated for leukemia at a specialty center. Preliminary findings suggest the diagnosis could be linked to an insertional event related to the treatment, Orchard announced.
“No additional patients will be treated with Strimvelis before the investigation is complete,” the company said in an emailed statement. When asked how long the probe might take, the biotech responded that an investigation is underway, and that more information will be available once it’s complete.
“Orchard has notified EMA of this event, and we remain in collaborative and ongoing dialogue with the agency,” spokesperson Christine Harrison said.
Strimvelis was approved in 2016 for patients with severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID). After attempting to sell off its gene therapy unit for months, GlaxoSmithKline traded it to Orchard in 2018 along with other gene therapy programs for a nearly 20% stake in the company.
The British drugmaker — and later, Orchard — struggled to find customers among the rare ADA-SCID patient population. To date, only 16 people have been treated with the drug since it was approved.
Back in May, the company reorganized to focus on more prevalent illnesses. It cut 25% of employees, halted the construction of a Fremont manufacturing facility, shut down a California R&D site, and divested two programs (another ACA-SCID gene therapy candidate and a transfusion-dependent beta-thalassemia candidate). When announcing the shakeup, Orchard said it would prioritize programs for metachromatic leukodystrophy (OTL-200), Wiskott-Aldrich syndrome (OTL-103), Mucopolysaccharidosis type I (OTL-203) and Mucopolysaccharidosis type IIIA, also known as Sanfilippo syndrome type A (OTL-201).
Orchard said that leukemia resulting from insertional oncogenesis is a known risk of gammaretroviral vector-based gene therapy, as described on the Strimvelis warning label.
The EMA’s product summary reads:
No cases of leukaemia or myelodysplasia have been reported following treatment with Strimvelis. However,vector insertions into chromosomal regions previously associated with leukaemia in comparable trials ofgene therapy in Wiskott Aldrich Syndrome, X-SCID and Chronic Granulomatous Disease have beendocumented. Retroviral insertion sites (RIS) have been detected adjacent to or within CCND2 and LMO2and there is a potential risk of leukaemic transformation following treatment with Strimvelis. It isrecommended that patients be monitored long term with at least annual visits for the first eleven years andthen at 13 and 15 years post treatment with Strimvelis, to include a complete blood count with differential,biochemistry and thyroid stimulating hormone.
Orchard’s stock has been on a steady decline since January, when shares reached a high of $15.71 apiece. They closed Friday at $4.04 per share.
Strimvelis’ future remains unclear. “The investigation is ongoing and the company will determine the future of Strimvelis following discussions with relevant stakeholders and will provide further updates as appropriate,” Orchard announced.
Social image: Bobby Gaspar, Orchard Therapeutics CEO