The US Food and Drug Administration (FDA) has lifted the clinical hold on a study of Juno Therapeutics’ lead CAR-T therapy, which will allow the biotech company to resume enrollment. The Phase II clinical trial was put on hold last week following the deaths of three patients receiving the immunotherapy.
Juno has revised the treatment protocol for the study – named “ROCKET” – to stop using the chemotherapy drug, fludarabine, which was implicated in the patient deaths. To pre-condition patients before they receive the CAR-T cell therapy, the study investigators will now exclusively use the cancer drug, cyclophosphamide.
Alongside Kite Pharma and Novartis, Juno has been a leader in the promising CAR-T therapy space. After three patients died following treatment with the company’s lead candidate – known as JCAR015 – many raised concerns about the cancer treatment’s safety.
JCAR015 was designed to treat patients with relapsed or refractory B cell acute lymphoblastic leukemia. The FDA’s clinical hold on the study was expected to be a major roadblock delaying, or even preventing, further development of JCAR015.
As Juno was quick to identify fludarabine as the likely culprit in the patient deaths, the FDA has given the company the go-ahead to continuing enrolling more patients in the clinical trial. Despite the quick turn-around, the delay could still affect Juno’s plans to apply for FDA approval in 2017.
“Our view is not that this toxicity was caused exclusively by this second chemotherapy called fludarabine that we added,” said Juno CEO Hans Bishop, on CNBC. “It is a combination of the strength of the chemotherapy we used with the cells.”
Last week, Juno submitted revised copies of its consent form, investigator brochure and trial protocol to the FDA, complying with the regulator’s request for this information. While the FDA has approved Juno’s request to continue with the ROCKET clinical trial, it’s still not certain how fludarabine – in combination with the CAR-T immunotherapy – led to the death of the three patients.
Juno conducted a previous CAR-T clinical trial using cyclophosphamide alone, and received positive results from that study. According to Bishop, JCAR015 still has the potential to be an effective treatment for patients with relapsed or refractory B cell acute lymphoblastic leukemia.
“Losing patients on a clinical trial is always more than a blip in the road. It is a sobering experience,” continued Bishop. “We are clearly figuring out how to best use these potent therapies. The promise of them, I think remains unchanged.”