Back in 2014, everyone wanted in on the CAR-T revolution. As news poured in of engineered T cells leading to complete remissions, so too did money from pharma: Celgene spent $1 billion to align itself with Juno Therapeutics; Amgen partnered with Kite Pharma with the promise of billions down the road; and Pfizer spent more than $100 million for the rights to an off-the-shelf CAR-T idea from Cellectis.

Flash to the present and Kite, now part of Gilead Sciences, has an approved product. Juno, since absorbed by Celgene, is not far behind. But Pfizer is tiptoeing back from the field, handing over the development of those off-the-shelf products to a startup run by the brains behind Kite.

A Pfizer spokeswoman said the company “will continue to participate financially and strategically” in the development of its cancer-killing cells, but the move seems to amount to an admission that off-the-shelf technology was too early-stage for a company the size of Pfizer. 

After the FDA refused to even review Alkermes’ mixed bag of data on a new depression drug, we asked readers whether Intra-Cellular Therapies, in a similar boat with its schizophrenia treatment, might suffer the same fate.

And 69 percent said yes, predicting that when Intra-Cellular goes to the FDA later this year, it will get the same cold shoulder that greeted Alkermes. The remaining 31 percent were more optimistic.

The recent spate of so-called refuse-to-file letters, in which the FDA stops the review process before it starts, serve as a counterpoint to what has become biotech dogma. Under Dr. Janet Woodcock, who has long led the FDA’s drug division, the agency has embraced flexible standards for approving new drugs. And Dr. Scott Gottlieb, appointed commissioner last year, has been a voluble advocate for streamlining the whole process.

But as Alkermes and Celgene can attest, that doesn’t mean anything goes at the FDA.

Regeneron Pharmaceuticals is having quite a time making money off of its new eczema drug in the U.S., where, despite winning over some watchdogs with a price deemed reasonable, the company is struggling to get prescriptions filled.

Now Sanofi, Regeneron's partner in Europe, is running into the same problem. As STAT's Ed Silverman reports, the U.K.'s drug pricing authority said the drug's $23,000 annual cost is "too high" for the National Health Services to pay for it.

It's a different problem than the one Regeneron faces in the U.S., where marketing success involves convincing a thicket of individual payers. But it's yet another sign that the world is shifting beneath the feet of biopharma companies that could once count on blockbuster sales so long as their drugs proved safe and effective.

STARTUP HEALTH INSIGHTS

There have been more digital health fundraising deals so far this year (191) than in all of 2010 (when there were 155) — the latest sign that investors are going gaga over the space. That's according to a new report from StartupHealth, which tracks accelerator and other seed funding, as well as venture, corporate venture, and private equity dollars. The biggest deals of the first quarter: $240 million for the cardiac monitoring company HeartFlow, $200 million for consumer genomics company Helix, and $165 million for the insurer Oscar. 

Keep in mind: More deals aren't necessarily translating to more dollars. Although there were 57 more deals this quarter compared with the first quarter of 2017, the total fundraising in the space, $2.8 billion, stayed flat year over year. (The first quarter of 2017, it's worth noting, was buoyed by the liquid biopsy company Grail's fundraise of nearly $1 billion.)

• High-flying biotech Loxo tempers bullish view for cancer drug. (Reuters)
• Biotech salvage operations come with red flags. (Bloomberg)
• Drug-loaded hydrogel responds to arthritis flare-ups in real time. (STAT)