ASH Roundup: CAR-T Shuffle, Hemophilia Updates, Checkpoint Progress & More

Xconomy National — 

Two years ago at the American Society of Hematology conference, excitement, not blood, was running in the streets of San Francisco. The cancer immunotherapy known as CAR-T was the star of the show, thanks to dazzling early data that showed more patients than not saw their leukemias and lymphomas knocked into remission by the living, genetically engineered cells.

For some developers the momentum continues, with two programs—one for non-Hodgkin lymphoma, one for kids with a type of leukemia—likely up for an FDA approval decision next year. But the field faces tough questions in months to come about patient deaths, in-house support, and—if the treatments come to market —tension over drug prices.

There was so much news about CAR-T and other T cell therapies at ASH, we’re rounding it up here. For everything else, read on.

Gene Therapy For Hemophilia

Potential gene therapies for hemophilia—an inherited disease that leaves patients unable to properly clot blood—continue to creep forward. Gene therapy offers the promise of a long-lasting treatment, and at ASH, Spark Therapeutics (NASDAQ: ONCE) and UniQure (NASDAQ: QURE) provided incremental updates.

Those data bring promise. At first exposure, patients are producing the clotting proteins the therapies are meant to trigger. Over time, patients are going longer without dangerous bleeding events and not relying on other drugs to boost clotting proteins.

Caveats remain. It’s more clear now that these gene therapies won’t work the same way for everyone. Some patients, for instance, develop an immune response that stifles the therapies and must be controlled with steroids. How long the gene therapy lasts in these patients, and others, is an important question.

At ASH, Spark said two patients in its Phase 1 trial have developed an immune response to its gene therapy, SPK-9001. The responses lowered both patients’ levels of replacement Factor IX, but so far those levels have not dropped low enough to cause bleeds or require other treatments. Succeeding on those measures without causing safety problems is what will ultimately make or break gene therapy in hemophilia. has more here, and here’s more on gene therapy in hemophilia.

Other Hemophilia News

—On its website, the Hemophilia Federation of America posts figures about the immune responses some patients develop against replacement clotting proteins like the ones sold by Baxalta and Bayer. The responses are most common in patients with severe hemophilia A—about 30 percent. The rates are much lower in people with mild or moderate hemophilia A (5 to 8 percent) and hemophilia B (2 to 3 percent).

Alnylam Pharmaceuticals (NASDAQ: ALNY) and Roche are developing drugs meant to help patients with these types of immune responses prevent bleeds. Roche’s emicizumab is in Phase 3 testing and has shown promise reducing bleeds, but has also led to dangerous clots. Alnylam is behind, presenting at ASH Phase 1 data for its RNA interference drug, fitusiran. So far, it’s shown the potential to reduce bleeds without significant safety problems. A few patients have seen a rise in liver enzymes, however, which could signal potential problems. Alnylam said the cases were reversible. Alnylam expects to begin a late-stage trial next year. Here’s more from Bloomberg.

Checkpoint Progress in Blood Cancer

—Cancer immunotherapy drugs known as “checkpoint” inhibitors, which help reveal tumors to the immune system, have started to change how cancers of the lung, skin, and bladder are treated. Progress in blood cancers has been slower. In May, the FDA approved Bristol-Myers Squibb’s nivolumab (Opdivo) for patients with a form of Hodgkin’s lymphoma who had failed prior treatment.  Merck’s pembrolizumab (Keytruda) could be approved for the same cancer in early 2017. And as OncLive reports, studies combining nivolumab or pembrolizumab with other drugs have showed early promise in Hodgkin’s, non-Hodgkin’s lymphoma, and chronic lymphocytic leukemia. Combination therapy will be important in multiple myeloma as well. Early data from one Phase 2 study combining pembrolizumab, pomalidamide (Pomalyst), and dexamethasone were presented at ASH as well.

Sickle Cell Disease

—Sickle cell disease affects 100,000 Americans and millions more worldwide. Only bone marrow transplants can cure it, but current transplant practices carry a lot of risk.

Only one drug, hydroxyurea—now generic—is U.S. approved to treat some sickle cell symptoms, which include strokes, deadly lung complications, bouts of excruciating pain, and anemia. At ASH, Oklahoma biotech Selexys Pharmaceuticals discussed Phase 2 data that had already made headlines last month, not only because its drug SelG1 seemed to reduce sickle cell-related pain episodes in a 198-person trial, but also because Novartis liked the data enough to buy Selexys for $665 million.

Bay Area Biotech Global Blood Therapeutics aims to treat the underlying cause with a once-a-day pill, taken for a lifetime, which reduces the sickling of blood cells. The firm released at ASH follow-up data to its Phase 1/2 study, and it should soon start a Phase 3 trial, with data to come in 2019.  Away from biotech, NIH-funded researchers reported that hydroxyurea was safe and showed signs of lowering the very high risk of stroke in African children with sickle cell. A Phase 3 trial is next.

More Multiple Myeloma

—Several new drugs have been approved for multiple myeloma the past few years, but there’s room to help folks who relapse. Newton, MA-based Karyopharm Therapeutics (NASDAQ: KPTI) is developing one possible option. The firm released updated results from its drug selinexor that’s being tested in patients who have failed four or five previous treatments. 16 percent of 78 evaluable patients in Karyopharm’s Phase 2 trial responded to treatment. The ratio was slightly higher for people who had failed at least five other times. Karyopharm says no other drugs have reported responses in this so-called “penta-refractory” group. Further results are expected in early 2018.

—Daratumumab (Darzalex) continued to prove its worth. The antibody drug from Johnson & Johnson (NYSE: JNJ) was approved in 2015 for patients who had failed at least three prior therapies but is working its way into earlier uses. The FDA recently approved daratumumab in a combination for patients who had failed at least one other therapy. At ASH, J&J provided more data from the study that formed the basis of the FDA’s latest decision. Here’s more at Targeted Oncology.

Anemia Ups and Downs

Myelodysplastic syndrome is the name for a group of disorders in which the bone marrow doesn’t produce enough healthy blood cells. MDS can cause anemia and other problems, like low numbers of infection-fighting white blood cells or blood-clotting platelets. Blood transfusions or anti-anemia drugs like Amgen’s epoetin alfa (Epogen) come with safety risks. Acceleron Pharma (NASDAQ: XLRN) and its partner Celgene (NASDAQ: CELG) are developing the infusable protein drug luspatercept, meant to reduce or eliminate the need for transfusions. Acceleron presented some Phase 2 data for luspatercept at ASH and is enrolling patients in a Phase 3 trial. has more here; Xconomy profiled Acceleron and its plans in 2014.

—Agios Pharmaceuticals (NASDAQ: AGIO) is developing a pair of drugs for pyruvate kinase deficiency, a genetic malfunction that causes a rare type of anemia with no approved treatments. The company has said it would pick only one of the two—AG-348 and AG-519—to advance to late-stage trials. Shares fell more than 12 percent on Monday after Agios disclosed at ASH a single case of liver inflammation in a patient on AG-519. Similar volatility hit earlier this year, when Agios presented early data on both drugs. FierceBiotech has more on the data; here’s more on the two drugs from Xconomy’s previous coverage in June.

Alex Lash and Frank Vinluan contributed to this report