voxelotor, from Global Blood Therapeutics (NASDAQ: [[ticker:GBT]]), which aims to boost a patient’s levels of hemoglobin. At ASH, doctors will dive into results from the first part of a Phase 3 voxelotor study that GBT discussed in brief earlier this year. Over 12 weeks, a higher dose of voxelotor boosted hemoglobin more than 1 gram per deciliter in 23 of 40 patients; placebo was only 4 of 44.
GBT has said it will ask the FDA for an early approval, even though plans fell through to record a more direct benefit—a reduction of pain crises. GBT will argue that the hemoglobin boost is tied to better health, similar to the correlation between lower cholesterol and better heart health. A meta-study at ASH looking at 20 years of sickle cell studies will bolster that argument. (Caveat: One of the five authors is a GBT official, and the lead author, the director of the University of Tennessee’s Center for Sickle Cell Disease, is an advisor to the company.)
HEMOPHILIA
Since the early 1990s, hemophiliacs have been able to treat their disease with chronic infusions of proteins, or factors, that help clot their blood. These drugs, typically infused at least once a week, have turned hemophilia into a manageable condition, but still stressful and expensive to treat. Things are changing. “We’re inching into the next generation of treatment,” says Mark Skinner, the former longtime president of the World Federation of Hemophilia, and a patient with the disease.
In the research presented at ASH this weekend, Skinner sees broad recognition that the standard of care just isn’t good enough.
Typical factor replacement therapy doesn’t give patients a steady amount of clotting protein. Levels wane through the next dose, leading to what Skinner calls “cycles of risk and protection.” That means patients with severe hemophilia have to be extra careful about “subclinical” bleeds they might not be aware are happening. Without treatment, subclinical bleeds can contribute to long-term health problems like joint damage. By preventing these bleeds, newer therapies could improve upon existing ones.
The first of the new wave is already here. Emicizumab (Hemlibra), from Roche is approved for hemophilia A and is a big advance. Patients with “inhibitors,” whose immune systems reject standard medicines, now have a new option to prevent bleeds. Emicizumab also provides a steady level of clotting protein, which may help some patients live life “relatively freely,” Skinner says.
Gene therapy could arrive within the next few years for both hemophilia A and the less common hemophilia B. Drug makers BioMarin Pharmaceutical (NASDAQ: [[ticker:BMRN]]), UniQure (NASDAQ: [[ticker:QURE]]), Pfizer (NYSE: [[ticker:PFE]]), and Spark Therapeutics (NASDAQ: [[ticker:ONCE]]) are all conducting late-stage clinical studies. If they work, will the effect eventually wear off? Why do some patients respond better than others? Will patients stick with the treatments they trust? And will insurers cover what could be $1 million-plus per-patient price tags?
That said, new data from gene therapies aren’t this year’s headlines. Instead, Skinner points to research on the impact of hemophilia on a patient’s life. If a patient is worrying less about subclinical bleeds, for example, perhaps she can be more active or avoid hospital trips or surgeries.
Multiple abstracts this year focus on the prevalence of those bleeds and how they change peoples’ lives, and on understanding the outcomes that really matter to hemophilia patients. Those studies could eventually help drug makers make better cases to payers or doctors.
Skinner has his eye on another presentation. Bioverativ, the ex-hemophilia business of Biogen now owned by Sanofi, is developing a factor replacement therapy for hemophilia A that might require less frequent injections. It’s not a major step forward like gene therapy could be, but Skinner believes it could be important for patients who aren’t candidates for gene therapy or who can’t get insurance coverage for emicizumab. Or perhaps they’re just more comfortable sticking with the kind of treatment they know. “It could nicely fill a space that moves us beyond where we are, and gives patients a range of options,” Skinner says.
MULTIPLE MYELOMA
A cancer of the plasma cells in the bone marrow, multiple myeloma is the third most common type of blood cancer behind leukemia and lymphoma, with 30,000 new U.S. cases a year and about 12,000 deaths. The good news is there are more treatment options and better outcomes for patients than ever before.
Over more than a decade, several drugs, led by lenalidomide (Revlimid), bortezomib (Velcade), and more recently daratumumab (Darzalex), have received approval. Combined with chemotherapy, they can knock myeloma into remission for longer periods of time. But myeloma, a persistent and lethal cancer, almost always returns.
A new weapon could emerge to help people who relapse, however: therapies that target a tumor protein called BCMA (B-cell maturation antigen). Several groups are developing CAR-T cell therapies to home in on cells that produce BCMA and wipe them out. Early experimental results have shown promise in patients who are running out of options. But there’s a looming question: How long do these treatments last? So far, there’s no solid answer.
The most advanced BCMA CAR-T program is from partners Bluebird Bio and Celgene. Investigators reported in June that half the 22 patients taking the highest available dose of bb2121 had no trace of cancer; median response of any kind averaged nearly 11 months. Celgene is going to test it, at that highest dose, head-to-head against standard combination regimens for patients who have failed other treatments. There is no update scheduled at ASH.
But ASH will feature a first look at a new version called bb21217. It’s been engineered to last longer in the patient (and kill more cancer cells); development of both versions will continue. In the ongoing Phase 1 trial of bb21217, the longest any patient has been on the therapy is six months. (Caveat: As with all data plucked from the abstracts, which were published in November, there could be notable updates during the presentation.)
Chinese firm Nanjing Legend Biotech is also in the mix, and, at ASH, will discuss an ongoing Phase 1 study of its LCAR-B38M conducted in China. According to the abstract, 42 of 57 patients have had a complete response with a median duration of 22 months.
Nanjing’s licensee Janssen, a unit of Johnson & Johnson (NYSE: [[ticker:JNJ]]), has started a Phase 1/2 trial in the U.S., with a minimum of $350 million riding on the results.
CAR-T isn’t the only new type of medicine going after BCMA. Different flavors of antibodies—ones that carry a cell-killing chemotherapy, ones that pull immune cells toward tumor cells, and more—are in early development. Amgen (NASDAQ: [[ticker:AMGN]]) will update progress on AMG-420, which grabs T cells by one receptor and myeloma cells via another.
As of May, the ongoing Phase 1 study testing a range of doses showed most promise at the 400 mg/dl dose of AMG-420. Five of six had at least partial responses, with three in total remission for at least 4.6 months. The study’s leaders will give an update at ASH. In addition to how long the drug’s benefit lasts, there’s another big question: Will anyone want to take it? One dose cycle requires being hooked up to an IV machine for four weeks straight, then two weeks off. Some patients in the study have received several cycles.
