Mark this year's American Society of Hematology meeting as one of the last times the biopharma community sees Celgene as an independent company.
The storied biotech is going out with a bang, however, with plans to release pivotal trial results for its leading cancer cell therapy lisocabtagene maraleucel, or liso-cel. Securing FDA approval of the drug by the end of 2020 is an essential step to its investors receiving $6 billion more from buyer Bristol-Myers Squibb.
An initial look at the data suggest liso-cel could be competitive with on-market rivals, but the disclosure of four deaths related to treatment appeared to give some on Wall Street pause. Patients treated with liso-cel — a chimeric antigen-receptor T cell, or CAR-T, therapy — are typically very sick, however.
Treatment-related patient deaths were reported in trials of Novartis' Kymriah and Gilead's Yescarta too, and that did not stop them from receiving FDA approval in a similar condition, large B-cell lymphoma.
Yet safety is Celgene's principal argument for why a third-to-market liso-cel, if approved, would be competitive. Moreover, trial deaths previously led to the abandonment of another CAR-T therapy from the same pipeline, JCAR015 from Juno Therapeutics, which Celgene bought for $9 billion less than two years ago.
On efficacy, the liso-cel data included in an abstract released Wednesday gave analysts cause for cautious optimism. In the trial, 268 lymphoma patients received liso-cel. Of the 255 whose tumors were evaluated, 73% saw their tumors shrink or disappear, with 52% achieving compete remission. Median duration of response, a key metric for gauging how long treatment benefit extends, was 13.3 months.
That looks on a par with Yescarta's response and complete remission rates of 72% and 51%, and better than Kymriah's 50% and 32%.
Of all 268 patients infused with liso-cel, 42% developed cytokine release syndrome (CRS), an inflammatory response that is common in CAR-T patients, and 2% had severe CRS. Some 30% had neurological side effects, 10% severe. These side effect rates were notably lower than what was observed in the trials of Yescarta or Kymriah that supported approval.
A tolerable CRS and neurotoxicity profile is essential to using CAR-T in the outpatient, rather than inpatient, setting, something Celgene hopes liso-cel could support.
Comparing CAR-T therapies in lymphoma
|Trial||Transcend NHL 001||Juliet||Zuma-1|
|Therapy||Liso-cel (n=255)||Kymriah (n=68)||Yescarta (n=101)|
|Overall response rate (n)||73% (186)||50% (34)||72% (73)|
|Complete response rate (n)||53% (135)||32% (22)||51% (52)|
Source: ASH 2019 abstracts, FDA labels
RBC Capital Markets analyst Brian Abrahams called liso-cel's data "supportive of competitive efficacy and potentially best-in-class safety" for treatments in this class.
Celgene has said it plans on submitting its application to the Food and Drug Administration by the end of 2019, a step toward securing approval by the end of 2020.
An approval by then would complete one of three milestones required to trigger an extra $9-a-share payout from Bristol-Myers to Celgene shareholders under the "contingent value right" that will be issued at the close of the transaction.
Because Kymriah and Yescarta are already on the market, Mizuho analyst Salim Syed expressed skepticism that liso-cel will qualify for an FDA Priority Review, which would shorten the approval timeline from 10 months to six.
Beyond liso-cel, Celgene's pipeline must hit two other milestones: approval of the multiple sclerosis drug ozanimod by the end of 2020 — the FDA has set a March 25, 2020 decision deadline — and approval of another blood cancer CAR-T therapy, idecabtagene vicleucel, by March 31, 2021.
Ide-cel, previously known as bb2121, is the one that looks least certain. Celgene says more data from the pivotal KarMMa trial in multiple myeloma will be out by the end of 2019, but not at ASH. An application will be delivered to the FDA by early 2020 and an approval decision is expected by the end of 2020, according to the drugmaker.
Keeping to that ide-cel timeline will be most sensitive to Bristol-Myers' execution post-acquisition, something that has bedeviled holders of CVRs before. The project also has a competitive threat from within Celgene's own pipeline in the guise of bb21217, which like ide-cel is advancing under a collaboration with Bluebird bio, not to mention Johnson & Johnson's JNJ-4528.