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Rare Blood Disease Innovations Address Unmet Needs, According To ASH Data

Innovations in rare blood disorders took center stage at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition, with key research presented on immune thrombocytopenia, hemophilia, and multiple myeloma.

Innovations in rare blood disorders took center stage at ASH 2024.

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Innovations in rare blood disorders took center stage at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition, with Sanofi highlighting 49 abstracts, including 9 oral presentations, featured at the conference in San Diego.1 Key research was presented on immune thrombocytopenia (ITP), hemophilia, and multiple myeloma (MM), among other disease states.

With new findings related to approved and investigational therapies alike, the diverse portfolio demonstrates the extent of unmet needs across rare blood disorders while making strides in addressing them.

Transformative Data Across Rare Blood Diseases Immune Thrombocytopenia: LUNA 3 Phase 3 Study Results

Investigators unveiled positive efficacy, safety, and quality of life outcomes from the LUNA 3 phase 3 study, which evaluated rilzabrutinib (PRN1008) for ITP. As a first-in-class oral, reversible, covalent Bruton tyrosine kinase (BTK) inhibitor, rilzabrutinib represents a potential breakthrough in treating ITP. While still under clinical investigation, the study's findings highlighted its promise for future care paradigms.

The first set of LUNA 3 data were derived from 202 randomized patients; 65% of those treated with rilzabrutinib achieved a platelet response compared with 33% in the placebo group, with 23% meeting the primary end point of a durable platelet response.2 In contrast, no placebo patients achieved this milestone (P < .0001). Rilzabrutinib also reduced the need for rescue therapy by 52%, improved physical fatigue and bleeding scores, and achieved a median time to initial platelet response of 15 days in responders. Adverse events were predominantly mild to moderate, with comparable rates of serious adverse events across both groups.

The second set of LUNA 3 data showed that improvements extended across multiple health-related quality-of-life (HRQoL) domains, including psychological health, overall HRQoL, symptoms, and social activity.3 Rilzabrutinib also enhanced health status (EQ-VAS), further highlighting its benefits beyond platelet count normalization. These findings suggest that rilzabrutinib may address both clinical and quality-of-life aspects of ITP.

Advancing Hemophilia Care

New data were presented from the ATLAS-OLE phase 3 study of fitusiran, an investigational antithrombin-lowering therapy for patients with hemophilia A or B, including those with inhibitors.1 Fitusiran's pivotal data, which demonstrated significant bleed protection, was complemented by findings on its management potential. The therapy is under regulatory review in the US and China, with a target FDA action date of March 28, 2025.

Additionally, data from ALTUVIIIO's XTEND-1 phase 3 study emphasized its impact on joint health and quality of life in patients with severe hemophilia A. Interim outcomes from the XTEND-ed phase 3 extension study further bolstered its long-term efficacy profile.

Groundbreaking Advances in Multiple Myeloma Front-Line Therapy: Sarclisa in Combination Regimens

ASH data highlighted the role of isatuximab (Sarclisa) in front-line therapy for multiple myeloma (MM). A key aspect of the data was exhibited in the IMROZ phase 3 study, exploring minimal residual disease (MRD) negativity in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) and treated with isatuximab in combination with bortezomib, lenalidomide, and dexamethasone (VRd).

Part 1 of the German-speaking Myeloma Multicenter Group (GMMG)-HD7 phase 3 study evaluating isatuximab with lenalidomide, bortezomib, and dexamethasone (RVd) in patients who were transplant-eligible NDMM was featured in a pair of oral presentations. These results reinforce isatuximab's potential to improve outcomes across multiple patient populations.

Expanding Research Horizons

Interim results from the ISAMYP phase 2 study showcased isatuximab's potential in relapsed AL amyloidosis when combined with pomalidomide and dexamethasone (Pd). While investigational, these data pave the way for broader applications of isatuximab beyond MM, Sanofi stated. Additionally, ongoing research into NK Cell Engagers (NKCE) underscored the company's focus on novel therapeutic strategies.

A Vision for Transforming Care

"The breadth of data featured at ASH reflects our decades-long commitment to advancing first and best-in-class medicines in rare blood diseases," Dietmar Berger, MD, PhD, chief medical officer and global head of Development at Sanofi, said in the statement. "From new phase 3 data for rilzabrutinib to continued progress for Sarclisa in multiple myeloma, our work demonstrates a relentless pursuit of evolving care for people living with these challenging conditions."

References

1. ASH: new data underscore Sanofi's commitment to innovation in rare blood diseases and cancers. News release. Sanofi. December 3, 2024. Https://www.News.Sanofi.Us/2024-12-03-ASH-New-data-underscore-Sanofis-commitment-to-innovation-in-rare-blood-diseases-and-cancers

2. Kuter DJ, Ghanima W, Cooper N, et al. Efficacy and safety of oral Bruton Tyrosine Kinase inhibitor (BTKi) rilzabrutinib in adults with previously treated immune thrombocytopenia (ITP): a phase 3, placebo-controlled, parallel-group, multicenter study (LUNA 3). Presented at: 66th ASH Annual Meeting & Exposition; December 7-10, 2024; San Diego, CA. Abstract 5.

3. Ghanima W, Liebman HA, Hu Y, et al. Improved health-related quality of life (HRQoL) with oral Bruton Tyrosine Kinase inhibitor (BTKi) rilzabrutinib vs placebo in adults with previously treated immune thrombocytopenia (ITP): phase 3 LUNA 3 multicenter study. Presented at: 66th ASH Annual Meeting & Exposition; December 7-10, 2024; San Diego, CA. Abstract 2552.

Research Shows New Treatment Could Delay Cancer Progression In Patients With High-risk Smoldering Multiple Myeloma

A new treatment is showing promise for people with high-risk smoldering multiple myeloma (SMM). This precancerous condition can progress to active multiple myeloma, a type of blood cancer. High-risk SMM carries a higher likelihood of progression.

Results from a phase 3 clinical trial, published in the New England Journal of Medicine and presented at this week's American Society of Hematology meeting, demonstrated that daratumumab, a monoclonal antibody that targets CD38, a protein found on the surface of myeloma cells, significantly reduces the risk of progression to active multiple myeloma and improves overall survival compared to active monitoring.

Smoldering multiple myeloma is a condition in which abnormal plasma cells accumulate in the bone marrow but do not display symptoms of active multiple myeloma. High-risk SMM, however, carries a significant risk of progressing to active disease. Until now, there has been no approved treatment for this high-risk group.

The multicenter, international AQUILA study randomly assigned 390 patients with high-risk SMM to receive either daratumumab or active monitoring. After a median follow-up of 65.2 months, the study demonstrated a 51% reduction in the risk of disease progression or death for those receiving daratumumab. At five years, 63.1% of patients in the daratumumab group remained progression-free, compared to 40.8% in the active monitoring group. Survival at five years was also significantly higher in the daratumumab group (93% vs. 86.9%).

"These results are a major advancement in the treatment of high-risk smoldering multiple myeloma," says S. Vincent Rajkumar, M.D., hematologist, Mayo Clinic Comprehensive Cancer Center and lead investigator of the trial. "For the first time, we have a treatment option that can significantly delay or prevent the progression to active disease, improving the lives of patients and offering them a chance at a longer, healthier future."

While hypertension was the most common side effect, occurring in a small percentage of patients in both groups, no new safety concerns were identified with daratumumab.

"This study provides strong evidence for the use of daratumumab as a treatment for high-risk smoldering multiple myeloma," says Dr. Rajkumar, the Edward W. And Betty Knight Scripps Professor of Medicine in honor of Edward C. Rosenow III, M.D.

Patients should discuss this new treatment option with their healthcare team to determine if it is appropriate for their individual circumstances.

ASH24: Darzalex In Smoldering Myeloma, Merck's ADC Data And Novo's Sickle Cell Drug

This story was originally published on BioPharma Dive. To receive daily news and insights, subscribe to our free daily BioPharma Dive newsletter.

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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