With AQUILA data, Johnson & Johnson seeks first drug approval for treatment of smoldering myeloma

Treatment with daratumumab or J&J's Darzalex alone seemed 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. Those results are part of applications that J&J sent to the FDA and EMA for approval for Darzalex monotherapy to treat high-risk smoldering myeloma, and experts expect that regulatory agencies will give the application a "thumbs up," said Ola Landgren, a myeloma physician and researcher at the University of Miami who did not work on the study.

The study randomized 390 smoldering myeloma patients to either receive Darzalex or receive active monitoring. After a median of 65.2 months, patients who received Darzalex had a 51% reduced risk of disease progression or death, and progression-free survival at five years was 63.1% among patients who received the drug and 40.8% among patients who did not. Seventeen patients in the Darzalex group also achieved a complete response or better, according to the results published in the New England Journal of Medicine on Monday.

Treating patients with smoldering myeloma has long been a hotly debated topic among myeloma physicians, in part because clinicians weren't certain that early treatment benefitted patients; it's also often unclear which smoldering patients will go on to develop active myeloma. Those patients who are fated to develop multiple myeloma may need stronger therapy than Darzalex alone, argued Hearn Jay Cho, the CMO of the Multiple Myeloma Research Foundation, who wasn't involved with the work.

"If you try to do something light, attenuated, more tolerable, you undertreat the people who are on the cusp 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 standard treatment for smoldering myeloma.

Other physicians strongly disagreed. "You can't argue anymore that there is no benefit from early treatment," said Irene Ghobrial, a myeloma physician and researcher at the Dana-Farber Cancer Institute who didn't work on the study. She said she plans to use Darzalex in some of her smoldering patients, though she added she wasn't sure if everyone in the myeloma community will.

Blenrep's comeback story keeps rolling on

A combination treatment with the GSK drug Blenrep cut the risk of death by 42% among patients with relapsed or refractory multiple myeloma, according to interim data from the DREAMM-7 trial presented Monday. Based on the data so far, GSK projected that the median overall survival period will reach 84 months for the Blenrep arm compared to 51 months for the comparator.

As readers probably remember, Blenrep won accelerated approval from the FDA in 2020 as an advanced myeloma treatment. But after it failed in a confirmatory study, GSK withdrew it from the market.

GSK kept up the program, however, and with the success in DREAMM-7, as well as another study called DREAMM-8, it recently refiled Blenrep with the FDA. An approval decision is expected by next summer. The company has lofty ambitions for moving the drug into earlier lines of treatment as well.

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Emerging efforts to ease 'conditioning' before genetic treatments

The approval one year ago of two genetic medicines for sickle cell disease, including the first therapy powered by CRISPR gene editing, was a milestone for people living with a debilitating blood disease long neglected by the medical establishment. But access to the near-curative treatments has been slowed by their high cost and the complicated procedures required to administer them.

New research presented here highlighted emerging efforts to remove one of the most concerning obstacles for patients: a "conditioning" course of a highly toxic chemotherapy called busulfan required to eliminate diseased cells from the bone marrow and make room for the genetically modified cells.

"Busulfan conditioning is a very challenging part of the procedure that will hold a lot of patients back from getting treatment, and it should," said John Evans, CEO of Beam Therapeutics, which is developing a CRISPR-based therapy for sickle cell, and a softer conditioning regimen, also powered by CRISPR, that eliminates the need for busulfan.

Kura Oncology touts encouraging early-stage trial results for menin inhibitor in AML

Kura Oncology, riding high on promising results of a small molecule drug for acute myeloid leukemia, believes its therapy has blockbuster potential — even though it's facing stiff competition that includes a pharma giant and a biotech that has beat 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 those that drive cancer cells to grow and spread uncontrollably. During ASH, Kura announced Phase 1 trial results showing that 100% of newly diagnosed AML patients with mutations in the gene NPM1 had complete responses to its oral drug, ziftomenib, combined with an intensive chemotherapy regimen, while 83% of patients with rearrangements of the gene KMT2A had complete responses to this regimen and Kura's drug.

Ziftomenib was well tolerated at all doses studied, and 50 out of 51 patients taking ziftomenib and intensive chemo (cytarabine and daunorubicin) were still alive as of the Oct. 1 data cutoff.

"This truly has the potential to be game-changing," Troy Wilson, Kura's CEO, told STAT's Jonathan Wosen. "You are turning acute leukemia into a chronic, manageable condition like hypertension. That would be the goal."

Market analysts liked the news, with analysts for Cantor writing that this was a "best-case data update."

Johnson & Johnson is developing its own menin inhibitor. And Kura is facing competition from Syndax, a Massachusetts biotech that won approval last month for a menin inhibitor in relapsed or refractory AML patients with mutations in KMT2A. But Wilson argues that the greatest market opportunity is in the first-line setting, and he adds that Kura's drug doesn't affect heart rhythms or blood cell counts in the way that Syndax's drug does. Wilson believes ziftomenib could one day bring in $5 billion in U.S. sales, though that'll depend in part on the results of two global Phase 3 studies the company and its development partner Kyowa Kirin, will launch next year.

Information on Oxbryta's withdrawal still scant

Pfizer representatives attended but did not speak during a special meeting Monday set up to discuss the recent withdrawal of Oxbryta, its drug for sickle cell disease due to safety concerns. The lack of new information on what, exactly, happened with the drug left session attendees asking questions that couldn't be answered.

There's a "long list of questions" that Pfizer and regulators need to address, said John Strouse, a sickle cell disease expert from Duke University who chaired Monday's meeting.

Alexis Thompson, a pediatric hematologist at the Children's Hospital of Philadelphia, said timely disclosures of scientific investigations is necessary, but "clearly did not happen here."

A report from the European Medicines Agency is expected to be released later this month, although an FDA inquiry will likely take longer, Strouse added.

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