The US Food and Drug Administration (FDA) has placed a clinical hold on trials of two of REGENXBIO’s investigational gene therapies, for the treatment of mucopolysaccharidosis (MPS) type I, after a patient dosed was diagnosed with a brain tumour.
The hold has been placed on both RGX-111 and RGX-121, despite the adverse event (AE) only occurring in a single patient dosed with RGX-111.
In a Phase I/II study (NCT03580083) evaluating RGX-111, a five-year-old patient with MPS I, also known as Hurler syndrome, was diagnosed with an intraventricular CNS tumour during a routine brain MRI. The patient was asymptomatic and received intracisternal RGX-111 four years prior. The investigation is ongoing to determine if this serious AE is drug related.
Preliminary genetic analysis of the resected tumour detected an adeno-associated virus (AAV) vector genome integration event associated with overexpression of a proto-oncogene (PLAG1), which is known to be susceptible to chromosomal rearrangements. The AAV vector gene therapy is delivered directly to the brain.
There have been no other cases of neoplasm reported in the nine other patients treated with RGX-111 nor in the 32 patients with MPS type II, also known as Hunter syndrome, treated with RGX-121.
CEO of REGENXBIO, Curran Simpson, said he is surprised by the FDA’s decision to pause the RGX-121 programme, as well as the RGX-111 trial. Simpson said: "These are separate therapies, and the positive safety profile of RGX-121 in more than 30 patients treated, including those dosed nearly seven years ago, remains unchanged.
“Patient safety is our top priority, and we, our investigators, and the patient community remain confident in the benefit-risk ratio of RGX-121 and are highly encouraged by the meaningful efficacy profile demonstrated in the pivotal trial. RGX-121 presents an opportunity to address the urgent, significant unmet medical need in this ultra-rare disease community, and continued delay means continued neurodevelopmental decline in boys with MPS II."
REGENXBIO added that it has not yet received the full clinical hold letter and awaits additional details from the FDA.
The company’s stock price fell 28.4% on the update; from a 27 January close of $13.41 to a 28 January open of $9.60. The company has a market cap of $566m.
This news came on the same day that Intellia Therapeutics had a clinical hold of its gene therapy nex-z lifted after a patient died in a Phase III trial. The hold has been lifted in the MAGNITUDE-2 trial but remains in place on the MAGNITUDE study.
