ASH24: Darzalex in smoldering myeloma, Merck’s ADC data and Novo’s sickle cell drug

This weekend, thousands of researchers and physicians descended on San Diego for the American Society of Hematology’s annual meeting. While BioPharma Dive wasn’t on site this year, we’ve summarized a few of the most notable datasets from the past two days below.

Darzalex in smoldering multiple myeloma

Johnson & Johnson and Genmab’s multiple myeloma drug Darzalex reduced the risk of disease progression by 51% among people with the pre-symptomatic, or “smoldering,” form of the disease, when compared with those who were only actively monitored for progression, according to new data presented at ASH on Monday.

There are no approved treatments for smoldering multiple myeloma; patients are typically checked regularly through blood tests and other assessments. In a trial called AQUILA, J&J enrolled 390 people with smoldering myeloma at high risk of progression and randomized about half to receive Darzalex, with the others only monitored for progression. Patients were then evaluated for a median of nearly five and a half years.

After five years, 63% of trial participants treated with Darzalex were alive and hadn’t progressed, compared to 41% of those who were actively monitored. Of those receiving Darzalex, 93% were still alive after five years, versus 87% of those in the control group. J&J has already asked regulators in the U.S. and Europe to approve Darzalex for smoldering multiple myeloma. — Jonathan Gardner

BEAM-101 in sickle cell disease

Treatment with BEAM-101, a cutting-edge base editing therapy from Beam Therapeutics, spurred production of protective fetal hemoglobin in seven people with sickle cell disease who have been infused with the medicine and followed for at least one month. These data, presented at ASH on Saturday, expand on an initial look at data from the trial provided back in November.

The increase in fetal hemoglobin, which supplants the mutated, sickled form, led to resolution of patients’ anemia and improved other markers for red blood cell health. While follow-up is short, none of the seven trial volunteers have had a sickle pain crisis after “engraftment” of Beam’s therapy.

One patient died from lung toxicity that investigators judged related to pre-treatment conditioning with chemotherapy, a case Beam had disclosed back in November. “This was tragic, but not completely unexpected” given the known risks of the chemo, said study author Matthew Heeney, of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, in a statement from ASH. — Ned Pagliarulo

Zilovertamab vedotin in lymphoma

All but one of 35 people with a common form of lymphoma who completed treatment with an experimental Merck & Co. drug experienced a complete response, meaning no detectable cancer cells remained. The drug, called zilovertamab vedotin, was given in combination with a common lymphoma regimen known as R-CHP in the Phase 2 trial, which enrolled people with previously untreated diffuse large B-cell lymphoma.

One patient discontinued treatment after an initial cycle of therapy, and serious treatment-related side effects were reported in 11% of all patients. Based on the data, Merck chose the lowest tested dose to advance into Phase 3 testing. The company acquired zilovertamab vedotin, which targets a protein called ROR1, in a 2020 acquisition of VelosBio.

“We look forward to advancing our research of this investigational ROR1-directed antibody drug conjugate, which we believe has strong potential in multiple hematologic malignancies,” said Gregory Lubiniecki, head of oncology clinical research at Merck Research Laboratories, in a Sunday statement. — Ned Pagliarulo

Etavopivat in sickle cell disease

An oral drug from Novo Nordisk reduced the rate of pain crises in people with sickle cell by nearly half compared to placebo, results from a Phase 2 study presented at ASH over the weekend showed.

Treatment with the drug, called etavopivat, also resulted in a longer time to participants’ first pain crisis versus placebo and improved levels of the oxygen-carrying protein hemoglobin. Julie Kanter, the director of the adult sickle cell program at the University of Alabama at Birmingham and a study investigator, called the data “very encouraging,” in an ASH statement.

Notably, etavopivat works differently than other sickle cell medicines like hydroxyurea, potentially providing another option in patients for whom those medicines don’t work well. “It’s not going to be for everyone, so we need to see who it’s going to be best for and how it can be used in combination with other therapies, but it’s absolutely a step in the right direction,” said Kanter.

The study enrolled 60 teenagers and adults with sickle cell, who on average experienced more than three pain crises in the year before enrolling in Novo Nordisk’s trial. The company has a Phase 3 study of etavopivat already underway, and is planning a second in a “more diverse global population,” according to ASH. — Ned Pagliarulo

Anito-cel in multiple myeloma

Arcellx and Gilead Sciences on Sunday disclosed updated data for their experimental multiple myeloma cell therapy that Wall Street analysts believe show the treatment’s potential to surpass a market-leading therapy from J&J and Legend Biotech.

The results, which will be presented in detail at ASH Monday, show that 97% of patients treated with the therapy, anito-cel, in a Phase 2 trial responded to treatment, and 62% had no signs of disease after median follow-up of 9.5 months. There were also no instances of movement disorders caused by nerve damage, a cell therapy side effect that has concerned treating physicians.

The findings, which build on results disclosed in November, continue to show anito-cel’s “best-in-class potential,” wrote Jack Allen, an analyst at Baird. Allen thinks Arcellx and Gilead’s treatment will eventually be seen as a “dominant” player in multiple myeloma cell therapy, rather than a “second place” medicine behind J&J and Legend’s Carvykti.

Still, Leerink Partners analyst Daina Graybosch expects ongoing debate about anito-cel’s performance relative to Carvykti “to take years to resolve.” Those discussions center around whether Arcellx enrolled patients with a better prognosis than those in Carvykti’s key trial, and if anito-cel’s apparent differentiation on safety will materialize in real-world use, she wrote. — Ben Fidler

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