Patient dies in trial of Rocket gene therapy for heart condition

Dive Brief:

• A patient who received an experimental gene therapy developed by Rocket Pharmaceuticals has died following treatment, the company disclosed Tuesday.
• According to Rocket, the patient experienced what’s known as capillary leak syndrome, where plasma and proteins seep from blood vessels into surrounding tissue, and later died from an acute systemic infection.
• The Food and Drug Administration ordered the study’s halt Friday, while Rocket works with clinical trial monitors and other experts to investigate the cause. The company said it is focusing on a “novel immune suppression agent” it recently added to a pre-treatment preparatory regimen.

Dive Insight:

Rocket had proactively modified its pre-treatment regimen in attempt to reduce the risk of an immune response known as “complement activation,” which it previously saw evidence of in the Phase 2 trial.

Two patients received the immune suppression agent, company CEO Gaurav Shah explained on a conference call Tuesday morning. Rocket was able to reduce the treatment course the second patient received after seeing early signs of capillary leak syndrome in the first.

The company is now exploring whether the additional drug it used — a so-called C3 inhibitor — “may have influenced immune responses in an unexpected or paradoxical way,” said Shah, who noted that the only difference in protocol for these two patients was the change in preparatory regimen.

Shah said Rocket is confident there remains a path forward for its gene therapy, which is designed to treat a rare inherited disorder known as Danon disease. The condition results in the accumulation of sugars and certain cellular components in cardiac muscle, leading to heart failure and early death.

“This is a deeply tragic loss. We are committed to fully understanding the circumstances surrounding it objectively and neutrally,” said Shah. “We are also immensely grateful to the family for their contribution to this important clinical research and their commitment to help advance science for the broader Danon community.”

Now, however, Rocket must prove to the FDA, researchers and its investors that its treatment, dubbed RP-A501, remains safe. It’s a position many other gene therapy developers have found themselves in after unexpected patient deaths in trials.

So far, investors appear skeptical Rocket will have an easy answer. Shares in the company slumped by more than 60% in Tuesday morning trading, erasing hundreds of millions of dollars from the company’s market capitalization.

Rocket emphasized that the introduction of the new immune agent was limited only to the Danon program, and not used in the company’s other pipeline projects. The company said it can’t predict when it may be able to resume the Phase 2 trial, which was expected to enroll 12 patients. 

RP-A501 is built around a version of the gene, called LAMP2B, that’s mutated in people with Danon. The replacement DNA is encased in an engineered viral shell known as an adenovirus-associated serotype 9 capsid. The therapy is infused, and is meant to be a one-time treatment.