Table of Contents
This summary of news from the ASH 2024 conference first appeared in STAT’s “ASH in 30” newsletter. Sign up here to receive future editions.
Welcome back, ASH followers. Here’s your recap of Monday’s news.
By the way, it will always be an impressive sight to see huge naval ships leaving the harbor just behind the convention center.
With the AQUILA data, Johnson & Johnson aims to achieve the first drug approval for the treatment of smoldering myeloma
Treatment with daratumumab or J&J’s Darzalex alone appeared to improve outcomes for patients with high-risk smoldering myeloma, a condition that precedes multiple myeloma, in the primary results of the randomized phase 3 AQUILA trial. These results are part of the applications J&J has sent to the FDA and EMA for approval for Darzalex monotherapy for the treatment of high-risk smoldering myeloma, and experts expect regulators will give the application a “thumbs up,” says Ola Landgren, a myeloma doctor. and researcher at the University of Miami who did not participate in the study.
In the study, 390 patients with smoldering myeloma were randomized to Darzalex or active monitoring. After a median of 65.2 months, patients receiving Darzalex had a 51% lower risk of disease progression or death, and five-year progression-free survival was 63.1% among patients receiving the drug and 40.8% among patients who didn’t get it. Seventeen patients in the Darzalex group also achieved a complete response or better, according to results published Monday in the New England Journal of Medicine.
Treating patients with smoldering myeloma has long been a hotly debated topic among myeloma doctors, in part because doctors were unsure that early treatment would benefit patients; it is also often unclear which smoldering patients will develop active myeloma. The patients destined to develop multiple myeloma may need stronger therapy than Darzalex alone, argued Hearn Jay Cho, the CMO of the Multiple Myeloma Research Foundation, who was not involved in the work.
“If you try to do something light, debilitating and more tolerable, you are undertreating people who are on the brink of multiple myeloma. This is the dilemma,” he said. The data are exciting, Cho said, but he felt there are still challenges before adopting this as the standard treatment for smoldering myeloma.
Other doctors strongly disagreed. “You can no longer argue that there is no benefit from early treatment,” said Irene Ghobrial, a myeloma physician and researcher at the Dana-Farber Cancer Institute, who did not participate in the study. She said she plans to use Darzalex on some of her smoldering patients, although she added that she wasn’t sure if everyone in the myeloma community would do that.
Read more.
Blenrep’s comeback story continues
Combination treatment with the GSK drug Blenrep reduced the risk of death by 42% in patients with relapsed or refractory multiple myeloma, according to interim data from the DREAMM-7 trial presented on Monday. Based on data to date, GSK predicts that the median overall survival period will be 84 months for the Blenrep arm, compared to 51 months for the comparator group.
As readers likely recall, Blenrep received accelerated approval from the FDA in 2020 as an advanced myeloma treatment. But after it failed in a confirmatory trial, GSK pulled it from the market.
However, GSK continued with the program and thanks to the success of DREAMM-7 and another study called DREAMM-8, it recently resubmitted Blenrep to the FDA. An approval decision is expected by next summer. The company has great ambitions to also introduce the drug into earlier treatment lines.
Read more.
Emerging attempts to facilitate ‘conditioning’ prior to genetic treatments
The approval a year ago of two genetic drugs for sickle cell disease, including the first therapy made possible by CRISPR gene editing, was a milestone for people living with a debilitating blood disorder long neglected by the medical community. But access to the virtually curative treatments is slowed by their high cost and the complicated procedures required to administer them.
New research presented here highlights emerging efforts to remove one of the most worrisome obstacles for patients: a “conditioning course” of a highly toxic chemotherapy called busulfan, which is needed to eliminate diseased cells from the bone marrow and space to make the genetically modified cells.
“Conditioning with busulfan is a very challenging part of the procedure that will prevent many patients from receiving treatment, and so it should be,” said John Evans, CEO of Beam Therapeutics, which is developing a CRISPR-based therapy for sickle cell disease. a gentler conditioning regimen, also enabled by CRISPR, which eliminates the need for busulfan.
Read more.
Kura Oncology touts encouraging early-stage trial results for menin inhibitor in AML
Kura Oncology, which is riding high on the promising results of a small-molecule drug for acute myeloid leukemia, believes its therapy has blockbuster potential even as it faces stiff competition, including a pharmaceutical giant and a biotech that has beaten it in a race for regulatory approval.
The San Diego biotech is developing a molecule that inhibits menin, a protein that regulates the production of other proteins, including proteins that cause cancer cells to grow and spread uncontrollably. At ASH, Kura announced phase 1 trial results showing that 100% of newly diagnosed AML patients with mutations in the NPM1 gene had a complete response to the oral drug, ziftomenib, combined with an intensive chemotherapy regimen, while 83% of patients with KMT2A gene rearrangements responded completely to this regimen and Kura’s drug.
Ziftomenib was well tolerated at all doses studied, and 50 of 51 patients taking ziftomenib and intensive chemotherapy (cytarabine and daunorubicin) were alive at the time of data cutoff on October 1.
“This really has the potential to be a game changer,” Kura CEO Troy Wilson told STAT’s Jonathan Wosen. “You turn acute leukemia into a chronic, manageable condition like high blood pressure. That would be the goal.”
Market analysts welcomed the news, with Cantor analysts writing that this was a “best-case data update.”
Johnson & Johnson is developing its own menine inhibitor. And Kura faces competition from Syndax, a Massachusetts biotech company that last month received approval for a menin inhibitor in relapsed or refractory AML patients with mutations in KMT2A. But Wilson argues that the biggest market opportunity is in the first-line setting, adding that Kura’s drug does not affect heart rhythm or blood cell counts the way Syndax’s drug does. Wilson believes ziftomenib could one day generate $5 billion in U.S. sales, although that will depend in part on the results of two global Phase 3 trials that the company and its development partner Kyowa Kirin will launch next year.
Information about Oxbryta’s withdrawal is still scarce
Pfizer representatives were present but did not speak at a special meeting set up Monday to discuss the recent withdrawal of sickle cell disease drug Oxbryta due to safety concerns. The lack of new information about what exactly happened when the drug session participants asked questions that could not be answered.
There is a “long list of questions” that Pfizer and regulators need to answer, said John Strouse, a sickle cell disease expert at Duke University who chaired Monday’s meeting.
Alexis Thompson, a pediatric hematologist at Children’s Hospital of Philadelphia, said timely disclosures about scientific research are necessary but “clearly didn’t happen here.”
A report from the European Medicines Agency is expected to be released later this month, although an FDA investigation will likely take longer, Strouse added.