Juno Therapeutics (JUNO) reminds investors yet again that the business of biotech -- developing new medicines that are effective and reasonably safe -- is hard to get right.
Genetically engineering immune cells to recognize and kill cancer is no longer science fiction. It's real, and desperately sick patients, many with no medical options left, stand to benefit. But as we learned Thursday night, these powerful cellular therapies -- known as chimeric antigen receptor T-cells (CAR-T) -- still come with great risk.
Three leukemia patients treated with Juno's cellular therapy in a clinical trial died from brain swelling. The U.S. Food and Drug Administration stepped in to halt the trial until Juno figures out what went wrong and comes up with a fix.
There are, of course, multiple investment ramifications to consider now that Juno has run into a serious safety setback. Here are some thoughts and questions, in no particular order:
Juno is in a jam. Thursday night, the company conceded the trial halt means its lead CAR-T JCAR015 targeting leukemia won't be on the docket for FDA review and (hopefully) approval until 2018, a delay of one year. This pushed-back timeline assumes Juno has figured out what went wrong and can re-start the clinical trial relatively quickly.
Juno believes a more aggressive mix of chemotherapy used to pre-condition some patients for its CAR-T caused the deadly brain swelling. The fix, then, might be to revert back to a milder form of chemotherapy used previously, which hasn't caused brain swelling. But assuring Juno's CAR-T is safer could also diminish the therapy's efficacy.
What if Juno's explanation for the cause of the patients' deaths is wrong?
Not all CAR-Ts are alike. On Thursday's conference call, Juno went to great lengths to explain the safety issued tied to JCAR015 hasn't been observed in the rest of its cellular therapy pipeline. Will this assurance really make investors feel better?
Is this a Juno-specific problem or will investors also retreat from Kite Pharma (KITE) and Novartis (NVS - Get Report) , the two closest competitors developing CAR-T therapies? Kite, in particular, has been moving forward aggressively, trying to beat Juno to the market. [And Kite will, if all goes well.] Speed breeds mistakes, so will Kite stumble as well?
At the very least, Kite appears to be rejoicing in Juno's misfortune. Hours after Juno disclosed its problems Thursday night, Kite issued a press release touting the completion of patient enrollment into its own pivotal CAR-T clinical trial. It's hard to believe the timing of Kite's press release was coincidental, but even if it was, that's playing ugly.
Watch the FDA and its reaction to these patient deaths closely. Regulators take patient safety very seriously. Approving new drugs always comes down to benefit vs. risk. When new risks are discovered, even for cancer patients running out of treatment options, the FDA can and has become conservative.
The CAR-T stocks will be most affected when trading kicks back in Friday morning but will there be spillover effects into biotech stocks, generally? The current biotech bear market has been blamed largely on generalist fund outflows. How will they view the Juno situation?
Sell-side analysts Friday morning are largely minimizing Juno's setback and defending the other CAR-T stocks like Kite. Because that's what sell-side analysts almost always do.
Can we please stop with the cancer "moonshot" rah-rah-rah for awhile? This idea that we're going to write a big check (Sean Parker) or give some speeches (Joe Biden) and cure cancer is ludicrous.
Is there an alternate way to bring T-cells to the cancer-killing party without having to go through the complex machinations of CAR-T? Yes, there is. That's what bispecific antibodies do. Among Big Pharma, Roche (RHHBY) has been one of the biggest proponents of bispecific antibodies (and has also been a conspicuous non-joiner in the CAR-T rush). Amgen's (AMGN - Get Report) Blincyto is a bispecific antibody approved for certain types of blood cancer. There are other companies working on the technology, too.
Who remembers the Chiffon margarine commercial from the 1970s? "It's not nice to fool with Mother Nature." Well ... CAR-T, CRISPR, gene therapy -- amazing science all. But tread carefully.