The Phase II clinical trial of JCAR015 – known as ROCKET - was halted last week after the death of three acute lymphoblastic leukemia (ALL) patients prompted the US Food and Drug Administration (FDA) to issue a clinical hold.
The news saw Juno’s share price tumble more than 30% on July 8. The halt also had a negative impact on a number of fellow chimeric antigen receptor (CAR) T-cell therapy developers, notably Kite Phama and Bluebird Bio whose share prices fell 10% and 5%.
On July 12 Juno said it had been given the go ahead to restart the study under a revised protocol that removed the co-administered chemotherapy fludarabine, which the firm believes was responsible for the deaths. Juno’s share price increased 30% on the day of the announcement.
Positive risk/benefit profile
The prompt restart is good news CAR-T therapy developers according to Arnaud Foussat, CSO of TxCell who told us “it shows that the benefit/risks ratio of the CAR-T cell approach for treating cancer remains positive despite the safety concerns and the recent deaths.”
But Foussat urged the sector to learn from the incident and to redouble its efforts to develop better trial protocols, particularly regards patent conditioning with chemotherapy and dosage.
He added that: “Conditioning patients with chemotherapy prior to, or in concomitance with, CAR-T administration, is believed to potentiate cell engraftment and therapeutic potential.
“However, this conditioning can be associated with increased side effects. Conditioning regimens therefore need to be carefully adjusted to provide the best benefit/risk profile for cancer patients, and this appropriate balance will be an important factor in the success of CAR-T cell therapies."
TxCell is developing CAR-Treg based therapies using its ENTrIA platform, which directs regulatory cells (Tregs) harvested from patient blood sample to target autoimmune inflammatory diseases.
The firm was recently cleared to restart a trial of its own cell therapy Ovasave – a candidate treatment for Crohn’s disease – after addressing manufacturing concerns raised by French regulators.
Since this article was published Juno has announced that a fourth patient had died in the ROCKET study. The firm said its chief medical officer Mark Gilbert "mistakenly said “three” cases out of 129 rather than “four” cases" during a conference call on July 7.
The firm said: "This death was included in the data presented in an oral presentation at the American Society of Hematology meeting in December 2015 and included in Juno’s Annual Report on Form 10-K for the fiscal year ended December 31, 2015."