ASH24 Highlights: Darzalex for Smoldering Myeloma, Merck’s ADC Findings, and Novo’s Sickle Cell Treatment Developments

This weekend, a multitude of researchers and healthcare professionals gathered in San Diego for the annual meeting of the American Society of Hematology. Although BioPharma Dive was not present this year, we have compiled some of the most significant data highlights from the event below.

Darzalex for Smoldering Multiple Myeloma

The multiple myeloma therapy Darzalex from Johnson & Johnson and Genmab has shown to decrease the likelihood of disease progression by 51% in individuals suffering from the “smoldering” subtype of the disease compared to those who were merely monitored for progression, as per new findings shared at ASH on Monday.

Currently, there are no approved treatments available for smoldering multiple myeloma; thus, patients generally undergo regular assessments and blood tests. In the AQUILA trial, J&J recruited 390 participants identified at high risk for disease progression and allocated roughly half to receive Darzalex, while the rest were only monitored. The patients were observed for an average of nearly five and a half years.

At the five-year mark, 63% of the participants treated with Darzalex had survived without disease progression, compared to 41% of those who received only monitoring. Among the Darzalex group, 93% remained alive after five years, versus 87% of the control participants. J&J has already sought regulatory approval in both the U.S. and Europe for Darzalex’s application in smoldering multiple myeloma. — Jonathan Gardner

BEAM-101 for Sickle Cell Disease

BEAM-101, an innovative therapy using base editing technology from Beam Therapeutics, stimulated the synthesis of protective fetal hemoglobin in seven sickle cell disease patients who received the treatment and were monitored for a minimum of one month. These findings, presented at the ASH conference on Saturday, build upon initial observations shared last November.

The rise in fetal hemoglobin, which replaces the mutant, sickled form, resulted in resolution of anemia in patients and enhanced other indicators of red blood cell quality. Although the follow-up period is limited, none of the seven participants experienced a sickle cell crisis following the “engraftment” of Beam’s treatment.

One patient did succumb to lung toxicity deemed related to chemotherapy used in pre-treatment conditioning, a situation Beam had previously announced in November. “While tragic, this was not entirely unexpected” given the known risks associated with chemotherapy, commented study author Matthew Heeney from Dana-Farber/Boston Children’s Cancer and Blood Disorders Center in a statement at ASH. — Ned Pagliarulo

Zilovertamab Vedotin for Lymphoma

Out of 35 individuals with a prevalent form of lymphoma who completed the treatment with an experimental Merck & Co. drug, all but one achieved a complete response, indicating no detectable cancer cells remained. This drug, zilovertamab vedotin, was administered alongside a typical lymphoma regimen known as R-CHP in this Phase 2 trial involving previously untreated diffuse large B-cell lymphoma patients.

One patient opted out after an initial treatment cycle, and serious side effects related to the therapy were observed in 11% of the participants. Based on these findings, Merck has chosen the lowest tested dose for progression to Phase 3 trials. The company acquired zilovertamab vedotin, which targets a protein named ROR1, in a 2020 acquisition of VelosBio.

“We eagerly anticipate advancing our investigation of this ROR1-directed antibody drug conjugate, which we believe possesses significant potential across various hematologic malignancies,” stated Gregory Lubiniecki, head of oncology clinical research at Merck Research Laboratories, in a Sunday release. — Ned Pagliarulo

Etavopivat for Sickle Cell Disease

In an ASH presentation over the weekend, Novo Nordisk’s oral medication reduced the frequency of pain episodes in sickle cell patients by almost 50% when compared to placebo, according to Phase 2 study results.

Patients treated with etavopivat experienced a longer duration before their initial pain crisis compared to those on placebo, along with improved levels of the oxygen-transporting protein hemoglobin. Julie Kanter, the director of the adult sickle cell program at the University of Alabama at Birmingham and a research investigator, referred to the results as “very encouraging” in a statement made at ASH.

It is important to note that etavopivat operates differently than established sickle cell treatments like hydroxyurea, potentially offering another alternative for patients who do not respond favorably to existing medications. “It may not be suitable for everyone, so we need to determine the optimal candidates and how it can be integrated with other therapies, but it’s certainly a positive advancement,” stated Kanter.

The participant pool for the study included 60 adolescents and adults with sickle cell, averaging more than three pain crises annually prior to entering the trial. Novo Nordisk is already conducting a Phase 3 study on etavopivat and intends to initiate a second trial in a “more diverse global population,” as reported at ASH. — Ned Pagliarulo

Anito-cel for Multiple Myeloma

On Sunday, Arcellx and Gilead Sciences revealed new findings concerning their experimental cell therapy for multiple myeloma, which analysts believe could outshine leading treatments from J&J and Legend Biotech.

The detailed results, to be presented at ASH on Monday, indicate that 97% of patients treated with anito-cel in a Phase 2 study showed a response to the treatment, while 62% exhibited no disease signs after a median follow-up of 9.5 months. Notably, no patients faced nerve damage-related movement disorders, a known side effect of cell therapies that raises concern among clinicians.

These findings, which are an extension of results shared in November, continue to validate anito-cel’s “best-in-class potential,” as suggested by analyst Jack Allen from Baird. Allen predicts that Arcellx and Gilead’s therapy will be recognized as a “dominant” option in multiple myeloma cell treatment rather than being seen as the “second choice” after Carvykti from J&J and Legend.

Nonetheless, Leerink Partners analyst Daina Graybosch anticipates that ongoing discussions about anito-cel’s efficacy in comparison to Carvykti “will take years to settle.” These conversations focus on whether Arcellx enrolled patients with statistically better prognoses than those in the pivotal trial of Carvykti, and whether anito-cel’s apparent safety advantages will be realized in clinical practice, as noted by Graybosch. — Ben Fidler