Capsida Biotherapeutics has paused an early-stage rare disease trial evaluating its lead gene therapy candidate, CAP-002, after the death of the first patient dosed in the study.
The death comes just two months after the Phase I/IIa trial began, which set out to determine the safety and efficacy of the adeno-associated virus (AAV) vector in paediatric patients with syntaxin-binding protein 1 (STXBP1) encephalopathy.
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The condition, which is estimated to impact one in 30,000 births, is commonly characterised by intellectual disability, early-onset seizures and spasticity. There are currently no disease-modifying therapies approved for the treatment of STXBP1 encephalopathy.
Though regulators did not enforce the pause on the CAP-002 SYNRGY study (NCT06983158), Capsida has chosen to temporarily stop trial proceedings while the company looks for the “root cause” of the patient death, which currently remains unknown.
In a public statement directed at the STXBP1 community, Capsida noted that the US Food and Drug Administration (FDA) had been informed about the patient death, and that the biotech will “work closely with partners and relevant experts” to assess the next steps for the gene therapy.
CAP-002, a singular intravenous (IV) infusion, is designed to restore normal expression of STXBP1 in the brain – a key gene involved in the communication between neurones. Through this mechanism, Capsida theorised that the gene therapy could correct seizures, motor abnormalities and developmental disabilities commonly associated with STXBP1 encephalopathy.
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By GlobalDataGene therapy toxicity remains a problem
During CAP-002’s early development, Capsida placed a keen focus on overcoming the safety concerns associated with other IV-administered gene therapies, touting the drug’s ability to “detarget the liver and dorsal root ganglia”.
This follows reports of off-target liver toxicity associated with certain therapies in this class – including Sarepta’s Duchenne muscular dystrophy (DMD) treatment, Elevidys (delandistrogene moxeparvovec). Following its FDA approval in 2023, the drug was in the regulatory spotlight after three patients died from acute liver failure following treatment.
However, Elevidys and CAP-002 are not the only gene therapies linked to patient deaths, as Rocket Pharmaceuticals’ Danon disease drug RP-A501 also triggered the passing of a patient in a Phase II trial after they suffered a fatal acute systemic infection.
It was a similar story for Neurogene’s Rett syndrome therapy, NGN-40, which saw a patient die from the complications of a rare hyperinflammatory syndrome associated with AAV over-exposure.
Alongside safety concerns, some investors are backing away from cell and gene therapy (CGT) projects due to scalability roadblocks and sky-high associated manufacturing costs. However, some companies in the space are still seeing success as Kriya Therapeutics closed a Series D funding round earlier this week worth $320m to advance its gene therapy pipeline.
Despite the lull in CGT investor funding in previous years, CGT experts believe that the sector may be on a correction course, as regulators warm up to the modality and manufacturing methods become more advanced.
