As court case looms, Bristol Myers touts label expansion for Breyanzi
As Bristol Myers Squibb braces for a court battle over a costly delay — at least for Celgene shareholders — for its CAR-T lymphoma treatment Breyanzi, the pharma giant is touting a label expansion in the second-line setting.
Breyanzi, also known as liso-cel, snagged a win on Friday in adults with large B-cell lymphoma (LBCL) who: don’t respond to chemotherapy, or relapse within 12 months; don’t respond or relapse after 12 months; or are not eligible for hematopoietic stem cell transplant after chemo due to their age or comorbidities.
“With this new indication, Breyanzi is approved to treat the broadest relapsed or refractory large B cell lymphoma patient population,” Nick Botwood, BMS’ SVP of US medical affairs, told Endpoints News. “Breyanzi does represent a significant advancement of the current or previous treatment paradigm that has been in place for nearly 30 years.”
Breyanzi was one of the stars of BMS’ $74 billion Celgene buyout back in 2019 and was first approved last February to treat diffuse large B cell lymphoma in patients who have previously received two prior rounds of systemic therapy. At the time, BMS announced a wholesale price of $410,300. Last year, Breyanzi raked in $87 million, according to the company’s Q4 results.
The label expansion was based on pivotal data from two studies, dubbed TRANSFORM and PILOT. In the TRANSFORM study, Breyanzi more than quadrupled event-free survival — defined as time until death, disease progression, no response to therapy or the need for additional therapy — compared to a placebo (p<0.0001), according to BMS. About 66% of patients in the Breyanzi arm achieved a complete response, versus 39% in the placebo arm (p<0.0001).
Meanwhile, in the single-arm PILOT study, 80% of patients saw a response, while 54% of patients achieved a CR. That study enrolled 61 patients with primary refractory or relapsed LBCL who were not considered candidates for stem cell transplant.
BMS is looking to replace the current standard of care in this setting, which involves salvage chemotherapy followed by high-dose chemo and a stem cell transplant. While stem cell transplants are becoming more safe and effective, many second-line patients can’t tolerate salvage chemotherapy. According to BMS, about half of patients aren’t eligible for a transplant because of their age or comorbidities, and among those who are eligible, only a quarter are able to go through with it and see a long-term benefit.
“It’s a relatively small proportion of the whole. So Breyanzi, it really does provide a significant new treatment option for these patients,” Botwood said.
Back in April, Gilead’s Kite won approval for its CAR-T rival Yescarta in patients with LBCL who are refractory to first-line chemo, or who relapse within 12 months. Though it’s difficult to compare data across trials, the estimated 18-month EFS rate for Yescarta was 41.5%, compared to 17% in the placebo arm.
The competition here may come down to the safety details, as both drugs received a boxed warning for cytokine release syndrome (CRS) and neurologic toxicities. In the ZUMA-7 study evaluating Yescarta in the second line, Grade 3 or higher CRS and neurologic events were observed in 7% and 25% of patients, respectively, according to Kite.
In the PILOT and TRANSFORM studies, BMS said any-grade CRS was reported in 45% of patients, and any-grade neurologic events were reported in 27%. Grade 3 CRS was reported in 1.3% of patients, and Grade 3 neurologic events in 7% of patients, according to BMS.
“We did a pool analysis of the TRANSFORM and the PILOT study, and actually the occurrences of cytokine release syndrome were generally low-grade and mostly resolved quickly with standard protocols,” Botwood said.
Also on Friday, a federal judge ruled against BMS’ motion to dismiss a case alleging it purposely slow-rolled Breyanzi’s approval to avoid paying out $6.4 billion in contingent value rights (CVR) to Celgene shareholders.
Upon striking a deal to acquire Celgene, BMS put $6.4 billion into a CVR agreement that required an FDA approval for Zeposia, Breyanzi and Abecma, each by an established date. After the pharma giant came up 36 days late on the Breyanzi deadline, the CVR became worthless.
Last June, UMB Bank filed suit against BMS, accusing the company of purposely delaying Breyanzi’s development to avoid the payouts.