What: Shares of the chimeric antigen receptor (CAR) transduced T cell developers Kite Pharma (NASDAQ: KITE) and Juno Therapeutics (JUNO) both plunged by double-digits in after-hours trading Thursday after the FDA placed a clinical hold on Juno's lead CAR-T therapy, JCAR015, in adult patients with relapsed or refractory B cell acute lymphoblastic leukemia (ALL). Bellicum Pharmaceuticals (BLCM 37.08%), another top CAR-T developer, also saw its shares fall by nearly 5% as a result of this news.
The FDA's hold stems from two patient deaths in JCAR015's ongoing mid-stage trial, known as the ROCKET trial, last week. Juno's management said the culprit seems to be the recent addition of fludarabine to the pre-conditioning regimen. Fludarabine is a chemotherapy commonly used in the treatment of hematological malignancies like ALL, but was added to the mix in this case in order to enhance the expansion of the genetically modified T cells.
Although the biotech's clinical trials for its other CAR-T cell product candidates were not included in this clinical hold, Juno's plans to bring JCAR015 to market by 2017, and subsequently transform into a commercial operation, are now in serious doubt. Consequently, Kite's CAR-T product candidate,KTE-C19, indicated for aggressive non-Hodgkin lymphoma, now appears to be in the catbird seat in terms of being the first to market.
So what: CAR-T therapies have proven to be a double-edged sword. On the one hand, these therapies have led to unprecedented response rates in several hard-to-treat blood-based disorders. Even so, researchers have run into major roadblocks on the safety side of the ledger, culminating in the halt of Juno's pivotal trial for JCAR015. Despite the potentially deadly side effects, Kite and Juno have both decided to sally forth without a surefire safety mechanism in place, relying primarily on dosing schemes with their lead clinical candidates to control adverse events. And so far, that approach has proven to be shaky at best.
Now what: Juno is hoping to get this clinical hold lifted by proposing to the FDA to eliminate fludarabine from the trial protocol. While Juno may be successful in this effort, the bigger issue is that Kite and Juno's lead therapies are probably going to be relegated to the status of later lines of treatment, in the best-case scenario, due to these lingering safety concerns.
The good news is that Bellicum already seems to have the answer to the CAR-T safety dilemma. Bellicum's chemical induction of dimerization (CID) technology is specifically designed to make adoptive T cell therapies safer and more potent. The core issue is that this CID technology forms the basis for a best-in-class molecular switching platform that can be triggered by a small molecule called rimiducid. Clinicians can thus decide to enhance a therapeutic effect, or dampen it if a patient begins to show signs of a serious adverse event.
Although there are other molecular switching mechanisms in existence, and Juno is working on enhancing its own safety platform, Bellicum's CID technology has arguably shown the most promise to date. And at this stage in the game, it's starting to look like a molecular switching mechanism is going to be absolutely necessary in order for CAR-T therapies to break into more lucrative earlier lines of therapy. That's why my money remains on Bellicum to be the under-the-radar winner in this hotly contested space.