Capsida Biotherapeutics has paused a gene therapy trial after the first patient died. The biotech, which began the phase 1/2 study in July, took the action to give it time to determine the “root cause” of the death.
California-based Capsida launched the trial to assess CAP-002 in children with syntaxin-binding protein 1 (STXBP1) encephalopathy, a condition characterized by abnormal brain function and recurrent seizures. The biotech designed the adeno-associated virus therapy to “detarget” the liver and dorsal root ganglia while crossing the blood-brain barrier, enabling the company to hail a breakthrough in intravenous delivery.
Yet, the phase 1/2 trial immediately ran into problems. Wednesday, Capsida disclosed that the first patient to participate in the study has died. In a letter posted on the company's website and addressed to the STXBP1 community, the biotech said that it understands “this devastating news will raise questions and uncertainty,” adding that it is “working with urgency to gather information and find answers.”
“We have voluntarily paused the CAP-002 SYNRGY study while we determine the root cause of the patient’s passing,” Capsida said. “As we continue to work closely with our partners and relevant experts, we have alerted the FDA and will be providing them with a full report in compliance with regulations. Once this work is complete, we can begin to assess next steps with respect to this important program.”
The company is yet to share more information. Last month, Capsida published (PDF) a presentation in which the biotech projected that it would dose the first patient in the CAP-002 trial in the third quarter. The plan was to enroll six patients aged 18 months to seven years in the phase 1 portion of the trial and report efficacy data on the first participant in the first quarter of next year.
Capsida designed CAP-002 and the rest of its pipeline to avoid some of the safety concerns associated with other gene therapies. For some treatments in this class, intravenous administration has been linked to a risk of off-target effects, notably in the liver, and of immune responses. Capsida worked to overcome those problems and exited preclinical toxicology studies believing CAP-002 had a well-tolerated safety profile.
The company identifies capsids that target desired tissues and cells while detargeting undesired tissues by screening candidates in nonhuman primates. Capsida used its directed evolution platform to identify novel capsids for its STXBP1, Parkinson’s disease and Friedreich’s ataxia gene therapies. The biotech took the Parkinson’s program into the clinic last month.
AbbVie, CRISPR Therapeutics and Eli Lilly have all struck deals with Capsida, with AbbVie paying $40 million to take up its option on a Capsida-partnered gene therapy in January. The biotech also has an agreement with Kate Therapeutics, which Novartis acquired last year.