Celgene posts pivotal CAR-T data ahead of FDA filing

Celgene has posted data from a pivotal trial of its CAR-T therapy. The data look competitive against Gilead’s Yescarta and Novartis’ Kymriah, leading analysts to predict Celgene will win FDA approval next year.
Investigators administered lisocabtagene maraleucel (liso-cel), an anti-CD19 CAR-T, to 262 patients with large B-cell lymphomas. Among the 255 patients evaluable for efficacy, the complete response rate was 53%. The overall response rate came in at 73%, and the median duration of response was 13.3 months. 

The response rates are around 20 percentage points higher than those on the Kymriah label and one or two percentage points above the results achieved by Yescarta. As the three drugs were studied in different trials, factors other than their efficacy may account for the differences. 

Jefferies analysts think the liso-cel data are strong enough to get the drug to market.  

“All-in-all, results look in-line with our expectations of efficacy and safety, and we continue to think there is a very high probability of success for approval,” the analysts wrote in a note to investors.  

The approval of liso-cel would provide competition for Kymirah and Yescarta, which are already struggling to live up to commercial expectations. Gilead’s Kite thinks Yescarta is well equipped to take on the challenge of extra competition, pointing to the longer-term data generated on its CAR-T to argue it is in a stronger position than is suggested by the label information referred to above.

“Data are being compared to labeling approved in 2017 for Yescarta. When these data are compared to the more mature data from the ZUMA-1 analysis at two years, published in Lancet Oncology, more than 50% of patients were still alive, meaning that at a minimum of 24 months median overall survival had not been reached,” Ibrahim El-Houssieny, vice president and head, Kite global medical affairs, said in an emailed statement.

The case for approving liso-cel, formerly known as JCAR017, may be bolstered by safety data. While there were four deaths related to liso-cel, overall the rates of treatment-emergent adverse events were lower than in the Kymirah and Yescarta studies. 

Kite linked Yescarta to a 87% rate of neurotoxicity and a 13% rate of grade 3 or higher cytokine release syndrome (CRS) during development. The rates of neurotoxicity and grade 3 CRS in the liso-cel trial were 30% and 2%, respectively. Celgene was confident enough in the safety and tolerability of the drug to dose 25 people in the outpatient settings. 

Improved understanding of how to safely dose CAR-Ts may explain the differences between the data on liso-cel and Yescarta, which was developed while knowledge of the cell therapies was still at a very early stage. 

The study also provides evidence that Celgene is on top of the challenge of manufacturing liso-cel. The average time from the separation of white blood cells to the availability of liso-cel was 24 days. Celgene was unable to manufacture liso-cel for two patients and provided nonconforming products to 24 patients. Kite noted that it achieved a 99% success rate and 17-day manufacturing turnaround time in its pivotal CAR-T trial.

Those data points matter, because manufacturing is one area that could stop Celgene winning approval for liso-cel next year. Celgene needs to win approval by the end of 2020 to trigger a $9-per-share cash payout under the terms of its acquisition by Bristol-Myers Squibb. 

Editor’s note: This article has been updated with a statement from Kite.