Rocket Pharmaceuticals has safely treated three patients with its one-time Danon disease gene therapy, RP-A501, during a Phase II study following a protocol amendment triggered by a patient death.
Since the US Food and Drug Administration (FDA) gave Rocket the go-ahead to relaunch the pivotal, single-arm trial (NCT06092034) with an updated protocol back in August 2025, the biotech has dosed three patients – all of whom received a recalibrated dose alongside an immunosuppressive combination of rituximab, sirolimus and corticosteroids. The FDA originally put the study on ice due to a patient fatality linked to capillary leak syndrome, which occurred after Rocket added a complement C3 inhibitor to the treatment regimen without informing investors.
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Since the protocol changes, Rocket claims that no patients to date have experienced either capillary leak syndrome, blood vessel damage or any other serious adverse events (SAEs) following treatment with RP-A501. Because of these early signs of success post protocol amendment, Rocket’s CEO, Gaurav Shah, notes that the biotech is now in talks with the FDA to figure out how best it can treat additional patients and complete this pivotal trial “as promptly as possible”.
According to Rocket’s CMO, Syed Rizvi, the biotech selected the recalibrated Phase II dose “with the expectation that it will deliver potency consistent with the dose at which RP-A501 demonstrated meaningful efficacy in Phase I.”
“This recalibration accounts for the higher proportion of full capsids in the current drug product in the setting of Danon disease and was developed in consultation with leading experts and the FDA. We anticipate that the dose will preserve RP-A501’s therapeutic potential while optimising its benefit-risk profile,” Rizvi added.
Taking steps to treat Danon disease
With early pivotal study success in the bag, Rocket may be one step closer to using this Phase II study to form the basis of a possible approval for RP-A501 in Danon disease – potentially adding another medicine to its portfolio following the milestone approval of Kresladi (marnetegragene autotemcel) in rare primary immune condition, severe leukocyte adhesion deficiency (LAD).
If US regulators give RP-A501 the green light, it would become the first treatment to reach patients with the rare inherited condition, which is characterised by a buildup of waste in the body tissues caused by a mutation in a specific gene called LAMP2.
Because patients with Danon disease express a disease-causing version of LAMP2, they often experience muscle weakness, intellectual disability and the thickening of heart muscle over time – resulting in the common need for a heart transplant in impacted individuals early on in life and a poor long-term prognosis.
Rocket designed its viral gene therapy, RP-A501, as a ‘one-and-done’ treatment to deliver a copy of the functioning LAMP2B gene to the heart cells. The biotech theorises the gene therapy can reinstate cellular waste recycling to potentially restore or stabilise cardiac function.
Having taken some steps in a positive direction for RP-A501’s development programme, Rocket expects to provide an update on the gene therapy’s Danon disease programme in the second half of 2026.
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