he American Society of Hematology’s annual conference is the year’s biggest stage for the most consequential research in treating blood diseases, attracting doctors, drugmakers and investors eager to vet the latest clinical trial results.
This year’s meeting, hosted in New Orleans, put a spotlight on new kinds of antibody drugs for cancer, including some that home in on a novel target in multiple myeloma. It also featured important updates on Bluebird bio’s gene therapy for beta thalassemia and sickle cell disease, data for which have been a conference mainstay for nearly a decade. And a new kind of drug from Argenx was included in the meeting’s highlights, with updated results detailing another potential use of the biotechnology company’s medicine.
Read on for details and takeaways from the meeting over the weekend:
A new target in multiple myeloma
Like many new drug targets, its name is complicated and better off abbreviated. Known in full as G protein-coupled receptor, family C, group 5, member D, the protein found on cancerous plasma cells drew attention over the weekend as Johnson & Johnson unveiled new data for an experimental multiple myeloma treatment.
J&J’s therapy, called talquetamab, is a bispecific antibody aimed at both GPRC5D and a protein expressed by immune cells. Study results presented on Saturday and published in The New England Journal of Medicine suggest it could be the next promising drug to emerge in multiple myeloma — an area already of intense drugmaker interest.
Just under three-quarters of participants given a lower or higher dose of talquetamab in the Phase 2 portion of J&J’s study responded to treatment, with around a third of each group achieving remission of their cancer. Data showed skin- and taste-related side effects were common, but typically rated mild. Infections also occurred in more than half of patients on each drug dose, with 17% and 12% respectively graded as more severe.
Notably, among a group of patients who had either previously had cell therapy or another bispecific antibody, 63% responded to treatment with talquetamab. All participants had received at least three prior treatments, including other types of drugs.
“We need options for those patients,” said Ajai Chari, a study author and hematologist from the Tisch Cancer Institute at Mount Sinai in New York, in a press conference held by ASH. “This is the new unmet need in multiple myeloma.”
On Friday, J&J submitted an application for U.S. approval, meaning the drug could reach market in the near future. Should it win an OK, talquetamab would join a cell therapy and another, recently cleared bispecific antibody in J&J’s portfolio of multiple myeloma treatments. Both of those therapies bind to BCMA, a protein targeted by a wave of new drugs from Roche, Regeneron, AbbVie and Pfizer.
The fast-advancing pipeline could expand options for multiple myeloma patients, but also raise questions about how treatments should be sequenced and how future drug trials might best be designed.
“No one is going to be cured with one treatment,” said Craig Tendler, J&J’s global head of oncology late clinical development, in an interview. “We see these [new drugs] as being part of regimens that will be used as complementary mechanisms of action, based upon sequencing, trying to address specific patient subgroups and disease characteristics.”
Chari, from Mount Sinai, agreed. “Sequencing is really important, and it’s probably the thing that we do the least well in myeloma,” he said at the press conference. “We’ve been so busy adding drugs to the arsenal that [we’re] catching up to figure out the right sequences and unanswered questions.”
Drugs targeting GPRC5D, for instance, could offer an alternative to BCMA-binding treatments. “We’re looking at all of that, to try to figure out how to optimize the combination of these drugs in a highly effective regimen,” said Tendler.
Also at ASH, Roche and Bristol Myers Squibb presented data for a GPRC5D-targeting bispecific antibody and cell therapy, respectively.
Argenx’s second act
Last December, Argenx, a Dutch biotechnology company, won FDA approval for its first drug, securing clearance for Vyvgart in a rare condition known as generalized myasthenia gravis. One year later, data presented at ASH could help the company make the case for approval in another uncommon autoimmune disease: primary immune thrombocytopenia, or ITP.
Therapies already exist for ITP, which causes dangerously low platelet levels, but they have limitations.
“Current treatment options for ITP, while [there] are many, can be associated with comorbidities, unsatisfactory efficacy and duration of effect,” said Catherine Broome, a study author and associate professor of medicine at the Georgetown Lombardi Cancer Center in Washington, D.C., at an ASH press conference. “They can have a limited impact on quality of life measures.”
Vyvgart, also known as efgartigimod, could help when other therapies don’t work, study results presented Sunday suggest. In a Phase 3 trial of 131 patients with ITP who had received previous treatments, Argenx’s drug led to sustained platelet responses in 22% of study participants, versus 5% of those on placebo.
“One of the things that I think is very telling with efgartigimod is, no matter what subgroup we looked at, it showed a benefit over placebo,” said Broome.
Serious side effects were reported in 8% of efgartigimod-treated patients and nearly 16% of those who received placebo, but none were deemed to be drug-related. Other adverse events like bruising, headaches and blood in urine occurred at similar rates in both groups.
Argenx is developing a subcutaneous version of efgartigimod and expects to have results from a Phase 3 study testing that formulation in the second half of 2023. Shares climbed about 3% on Monday and, at about $400 apiece, trade near record highs.
A new limitation for Bluebird’s sickle cell gene therapy?
Bluebird got a much-needed lift this year when U.S. regulators approved two of its gene therapies. But neither are expected to give the cash-strapped company significant revenue, making a third program for sickle cell disease crucial to its future.
Testing of that drug, known as lovo-cel, has already been stalled twice by the Food and Drug Administration due to safety concerns, causing Bluebird to fall behind a rival gene editing treatment from Vertex Pharmaceuticals and CRISPR Therapeutics that’s now under rolling regulatory review in the U.S. Vertex and CRISPR aim to complete their filing by the end of the first quarter.
Bluebird also expects to file for approval early next year, and bolstered its case at ASH with a presentation intended to distance its gene therapy from two cases of persistent anemia among patients in its clinical trial. Anemia, in this context, can be worrisome as a potential sign of emerging blood cancer.
The cases occurred in one adult and one younger study participant. Bluebird attributed both to underlying genetics — specifically, a condition known as alpha thalassemia trait that is associated with anemia. No other study participants in the trial had the same genotype.
Bluebird believes lovo-cel may exacerbate the problems linked to alpha thalassemia trait. The adult patient, for instance, currently needs transfusions to handle her anemia and has “intermittent” bouts of chronic pain. The younger patient doesn’t, but Bluebird still plans to screen for patients with the alpha thalassemia trait in the future and exclude them from its ongoing studies.
The company hasn’t seen evidence of an emerging cancer, a top safety concern of treatments like lovo-cel, or other findings that would suggest the treatment is causing a problem. Additionally, updated results show that 31 of 32 patients in the pivotal portion of lovo-cel’s trial haven’t had a painful episode known as a vaso-occlusive crisis through at least two years of follow-up.
The new exclusion criteria could represent an “incremental headwind” for Bluebird should it get to market, wrote SVB Securities analyst Mani Foroohar. The number of patients it will impact is “difficult to quantify and likely modest,” Foroohar added, “but still real.”