Tuesday, May 29, 2018

The Readout by Damian Garde & Meghana Keshavan

Welcome to The Readout, where we keep you on top of the latest in biotech. For more in-depth coverage of biopharma, subscribe to STAT Plus. On Twitter: @damiangarde@megkesh, and @statnews. And, hey, ASCO is almost here. Sign up here for our pop-up newsletter.


Another blow for combination immunotherapy

Another day, another dropped combination immunotherapy trial. Two, actually: An uptick of “mortality-related events” in the combination arm of a Janssen Phase 1b/2 trial is leading the drug maker to scuttle any further study of a second early stage combination trial. 

Specifically, Janssen is ending its Phase 1 study of daratumumab in a multiple myeloma trial. Daratumumab — a multiple myeloma blockbuster from Danish biotech Genmab — was being studied in combination with a checkpoint inhibitor in Janssen's pipeline. The drug maker is also ending a Phase 1b/2 trial of the drug — sold under trade name Darzalex — in combination with atezolizumab, or Tecentriq, in patients with non-small cell lung cancer. 

Neither of the combination therapies showed any benefit. And the increase in these “mortality-related events” suggests that daratumumab may be a poor candidate for further combination study. 

Investors are already a bit spooked about the whole combination therapy rodeo: About two months back, Incyte had that failed Phase 3 trial, and much of the data from clinical trial research abstracts released by the American Society of Clinical Oncology appeared to be disappointing

A silver lining for multiple myeloma

Despite the aforementioned multiple myeloma trial flop, there's been tremendous progress in developing treatments for the disease in recent years. Drugs like Velcade (bortezomib), approved 15 years back, along with 20 other drugs approved since then, have transformed multiple myeloma from a death sentence into a long-term, chronic illness. 

The disease is now poised for another inflection point: Dozens of experimental drugs are being tested, aimed at reaching the one-quarter of patients who aren’t being helped by existing drugs. 

“There’s no question it’s a golden age in multiple myeloma drug development,” Dr. David Reese, a senior vice president at Amgen, told STAT. The company developed the drug Kyprolis (carfilzomib) and is testing five others.

Read more. 

Treating CAR-T's toxicities

Scientists are beginning to get to the bottom of why CAR-T therapies come with such dangerous toxicities: Two Nature papers outline different mechanisms that cause cytokine release syndrome and neurotoxicity. The work is based on rudimentary mouse models, of course, but it’s still useful insight into why these potent cell therapies can be so deadly — and suggests ways these adverse events might be mitigated. 

The first paper pinpoints macrophages, a form of white blood cells, as the real culprits for elevated cytokine levels — not the engineered CAR-T cells themselves. Specifically, it found that two cytokines — interleukin-6, interleukin-1, and nitric oxide produced by the macrophages helped lead to the fever, hypotension, and breathing problems associated with cytokine release syndrome.

The second paper suggested that human monocytes — a form of macrophage — were likely responsible for the symptoms. The study tested two rheumatoid arthritis drugs — Actemra and Kineret — in the mice, and found that the latter, in particular, “abolished both CRS and neurotoxicity.” 

Time to turn Trump's drug pricing promises into reality

President Trump’s big drug pricing speech has come and gone — and now it’s time to see some action. That, anyway, is the idea.
Now that cabinet officials have led the media blitz, a small coterie of deputies and experts further down on the agency totem poles are responsible for the actual drafts, designs, and implementation of the proposals.

STAT’s Erin Mershon takes a look at six of the key players in Washington charged with making it all happen.

China's biopharma boom

More proof that the biopharma market in China is hot, hot, hot: The country’s highest-performing stocks are drug makers, outpacing the performance of most other industries. 

And it’s not just fancy oncology players or generic drug makers that are winning the stock game: A company that turns snake gall bladders into drugs saw its shares more than double, Bloomberg writes.

As U.S. trade disputes become increasingly heated, Chinese investors are placing their dollars in health care. Indeed, Bloomberg estimates that as China's wealth skyrockets and its population ages, its health care industry will see 20 percent growth for the next three to five years. 

More reads

  • Senator, blocking subpoena of Teva in opioids probe, says matter should be left to courts (STAT)
  • Medical cannabis developer GW Pharma close to final breakthrough (The Times)

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