FOCUS ON CANCER: The news from ASH, bispecifics, payment woes, & off-the-shelf CAR-T
December 6, 2018
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News (fl)ASH  
The annual meeting of the American Society of Hematology is newsy, and the 2018 iteration in San Diego earlier this week was no exception . ASH conditions like sickle cell anemia and hemophilia are in the portfolio. So are blood cancers--leukemia, lymphoma, multiple myeloma--and many of the ASH headlines are about developments in the treatment for those diseases. 

Stat's  Adam Feuerstein wrote daily ASH round-ups. You can find his first "ASH in 30 Seconds" write-up here, his second day summary  here, and the third day here. All are worth more than 30 seconds of your time.  BioPharma Dive (especially BioPharma Dive), MedPage Today, Barron's, Bioworld, and  Vantage also supplied plenty of good coverage of the meeting. 

Bispecifics make a splash
Amgen, Roche and Regeneron, and others reported some positive results about their bispecific compounds at ASH.

Bispecifics? Ned Pagliarulo and Jacob Bell of Biopharma Dive have a lucid explanation: While most antibody-based immunotherapies are designed to latch on to the antigens that tumor cells sport on their surfaces, the bispecifics reach out and grab on to both  tumor and immune cells, effectively yoking them together so that T cells can then get down to their cancer-killing business.

Amgen's Blincyto (blinatumumab) is a bispecific. At ASH, results for Amgen's AMG420 garnered a lot of attention because of some preliminary but impressive results presented in September. The results reported at ASH were not quite as encouraging, in Pagliarulo and Bell's telling. Amgen's Greg Friberg told them that the people in the subjects were "highly pretreated" and that the bispecific may be more effective when it is sequenced after de-bulking agents.
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Sharpless, others: Treatment imperiled by quagmire of payment issues 
Not my job, Norman Sharpless says about payment. 

"That's a CMS problem," the NCI director told Feuerstein in an interview. Except when the payer issues put the future cancer cell therapies at risk-and, he said to Feuerstein, "I think we're there."

"I know of a number of programs where there are very promising Phase 1 or early Phase 2 trial data, but going forward with much larger studies is something that the industry and payers are nervous about," he continued. "They are seeing the reimbursement troubles we are having with CD-1
9 [CAR-T products like Yescarta and Kymriah] and they're wondering if there is a market there." 

In his speech at ASH , Sharpless changed the subject and called for aggregating genetic data of patients so the presence of genetic differences that might affect the efficacy of treatment might be detected sooner. 

Separately, a panel of hospital-based doctors and executives at ASH discussed the  complexities of reimbursement (and 1,000-page CMS documents they have to wade through) and the growing gap between CAR-T prices and Medicare and Medicaid reimbursement.
Good results for 'off-the-shelf' CAR-T
Speaking of Kymriah ( tisagenlecleucel) and Yescarta ( axicabtagene ciloleuce), they may soon be in for competition from cheaper, more convenient "off the shelf" CAR-T treatments. 

Kymriah and Yescarta are autologous treatments that involve modification of the patient's own T cells. Allogene Therapeutics, Atara Biotherapeutics, and Celyad in Belgium are developing allogeneic CAR-T treatments that use donor (aka allogeneic, thus Allogene) cells, which, metaphorically speaking, can be taken off the shelf. 

At ASH, Allogene reported results from a small (17 patients) Phase I trial that showed a good response rate to its off-the-shelf CAR-T therapy, UCART19. Allogene also presented data on ALLO-715, which targets a different antigen (BCMA instead of CD-19). 

And last week, before ASH got started, Celyad announced that its allogeneic CAR-T agent, CYAD-101, had been injected into the first patient in the treatment's Phase I trial.

These are early hours of the early days. But there are a lot of eyeballs on off-the-shelf CAR-T--and a lot of money chasing its possible success. Allogene has had great success getting venture capital investment this year and then topped it off with an IPO that brought in $324 million. 
Good results for Darzalex but not the right comparison
French researchers reported strong results for Darzalex (daratumumab) at ASH--that adding it to Revlimid (lenalidomide) extended progression-free survival. But a Mayo multiple myeloma expert, S. Vincent Rajkumar, told MedPage Today, hold on here, the trial did not compare the new regimen to the current standard of care, a combination of Velcade (bortezomib), Revlimid, and dexamethasone.
Peter Wehrwein
Editor 
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