New pediatric data shoot Rocket's gene therapy toward phase 2, leaving behind FDA concerns

Having overcome FDA trial issues last year, Rocket Pharmaceuticals expects the latest early-stage data for its heart disease drug to give the gene therapy a long-awaited boost into phase 2 trials.

Updates from the small phase 1 trial of RP-A501 now include data from two pediatric patients as well as four ongoing adult patients with Danon disease, showing that the one-time intravenous infusion led to an improvement across a number of heart-related markers. Danon disease, a rare disorder, is characterized by a weakening of the heart and skeletal muscles as well as intellectual disability.

The therapy hasn’t had a smooth ride, and these data come nearly two years after the FDA slapped a clinical hold on the therapy. After addressing the agency’s requests to modify the trial protocol and other supporting documents last August, Rocket was able to begin dosing the low-dose pediatric cohort.

The biotech hopes the latest phase 1 readout will persuade the regulator to let it move RP-A501 into phase 2 testing. Feedback from the agency on the trial design is expected later this year.

The data for the pediatric patients only go up to a nine-month follow-up, but the company said so far they are consistent with initial improvements observed in the adult patients, who have been followed for up to 36 months.

Rocket CEO Gaurav Shah, M.D., branded the findings “the most comprehensive investigational gene therapy dataset for any cardiac condition.”

Shah added in a Sept. 30 release that the company was “particularly excited” that the two pediatric and three adult patients with a closely monitored immunomodulatory regimen showed an improvement on the New York Heart Association’s classification system of heart failure, moving from class II to class I. The one adult who did not receive a closely monitored regimen saw their classification stabilize.

The trial data also looked at a number of other criteria, including brain natriuretic peptide (BNP), a key marker of heart failure. All patients saw either a stabilization or a meaningful decrease in their BNP, with the most significant changes seen in patients with higher baseline BNP, Rocket said.

When it came to high sensitivity troponin I, a protein in the blood that suggests cardiac injury, the two pediatric patients saw a drop of 90% and 85% after six and nine months, respectively. The four adults patients saw a reduction in troponin of over 75% from mean pretreatment baseline by 18 and 24 months. These reductions were maintained among three of the adults in 30- and 36-month check-ins.

“Simply put, these data indicate that these patients are no longer afflicted with cardiac disease symptoms during regular activity or cardiac-related limitations in physical activity,” Shah said in the release.

The low dose of RP-A501 was generally well tolerated across the pediatric and adult cohorts, said Rocket. The two pediatric patients received a modified immunomodulatory regimen to mitigate adverse events, the company noted. A previous readout from the trial in 2020 had revealed a drug-related serious adverse event in the higher-dose cohort.

The findings mark a second good week for Rockets’ heart-focused gene therapy plans, coming days after the company scooped up Renovacor.