In late May, a patient died after receiving Rocket Pharmaceuticals’ investigational gene therapy for Danon disease, spurring the hold. After lowering the dose and changing the regimen of immune modulators patients receive, the company has received FDA clearance for the trial to continue.
The FDA has lifted a clinical hold on a Phase II trial testing Rocket Pharmaceuticals’ investigational gene therapy for Danon disease, the company announced Wednesday.
The hold was placed in late May when a patient died after receiving RP-A501. The patient developed capillary leak syndrome, experiencing a large drop in blood pressure from fluids seeping out of blood vessels and into surrounding tissue.
Shares of Rocket were up about 14% at the time of publication.
According to the company’s statement, the trial can proceed using a “recalibrated dose” of the gene therapy that aligns with the lower range of effective doses tried in an earlier Phase I trial. Analysts at BMO Capital Markets, writing in a note Wednesday morning, pointed out that higher doses had not resulted in improved outcomes in that Phase I trial. In total, the trial has dosed six patients.
Rocket is also making other changes to the trial, including the addition of an immunomodulatory regimen similar to one used in a pediatric group in the Phase I trial. That trial dosed two patients aged between 11 and 14 years of age and five patients 15 years or older. All of the patients in the trial were male. Rocket is also dropping from the trial regimen a C3 complement inhibitor it was using as a prophylactic.
Jefferies analysts were encouraged by the FDA’s action, writing that “the clinical hold lift suggests the FDA is aligned with RCKT’s root cause analysis in that the [adverse event] was due to the addition of a new C3 inhibitor to the pretreatment regimen (e.g. an explainable death that can be prevented in the future).”
That it took just under three months for the hold to be lifted, where holds for gene therapies in the past have often lasted five or six months and as long as 12 months, "[highlights] FDA’s flexibility given high unmet need in DD” the BMO analysts wrote. That timespan signals “a collaborative and understanding CBER division led by Dr. Vinay Prasad,” who has repeatedly stated his desire to make treatments for rare diseases more accessible.
William Blair was similarly positive on the whole, especially on the three-month timeline. “However,” the group wrote, “we note that the protocol changes add some additional risk, including whether administration of the C5 inhibitor will be sufficient to prevent additional cases of thrombotic microangiopathy (TMA) and if the recalibrated dose will be sufficient to provide durable responses in adults with Danon disease.”
Danon disease is a rare, X-linked genetic disorder caused by a mutation in a single gene called LAMP2, resulting in build-up of glycogen and autophagosomes in heart muscle and other tissues, eventually leading to heart failure. Rocket estimates that there are between 15,000 and 30,000 patients with Danon disease in the U.S. and Europe. RP-A501 is an AAV-based gene therapy that delivers a functional copy of LAMP2 to heart muscle cells.
