FDA’s ODAC Rules Unanimously on a Faster Way to Approve Multiple Myeloma Therapies

MIAMI, FLORIDA (April 12, 2024) – An advisory committee at the U.S. Food and Drug Administration voted 12-0 today in favor of a major shift in how the agency evaluates new treatments for multiple myeloma. The FDA often adopts the recommendations of its expert committees, and if it accepts this change, the result will be faster approval of new treatments for multiple myeloma.

Physician-scientists from Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, presented their assessment of a newer way to evaluate treatments through measuring “minimal residual disease.”

If the FDA adopts this new endpoint, patients will gain quicker access to new therapies, said C. Ola Landgren, M.D., Ph.D., director of Sylvester’s Myeloma Research Institute. Landgren led the assessment, called the “EVIDENCE meta-analysis,” and presented the findings at today’s Oncologic Drug Advisory Committee meeting.

“The research and evidence presented by Dr. Landgren was impactful, positive, clear and convincing,” said Stephen D. Nimer, M.D., director of Sylvester. “The vote by the Oncologic Drugs Advisory Committee supporting the use of minimal residual disease to approve new multiple myeloma treatments will greatly speed up the development of new drugs for myeloma and help the thousands of patients with myeloma receive optimal therapy.”

Easing the pathway to approval for new cancer treatments has long been a priority for Landgren. He and his colleagues have worked for years with U.S. regulatory authorities to assess how to improve the evaluation of new treatments for multiple myeloma, the second-most common type of blood cancer.

A host of oncology treatments go through the FDA’s accelerated approval pathway, an expedited process for new drugs and biologics for serious or life-threatening diseases. Treatments taking this pathway must show an advantage over available therapy based on a biomarker or other endpoint that is likely to predict clinical benefit. Sometimes, drugs may have to clear a post-marketing study to confirm a benefit in the clinic, such as showing improved overall survival.

For years, the accepted endpoint for myeloma for the accelerated pathway has been a measurement called the overall response rate (ORR), based on a blood biomarker and other data. An increasing number of newly diagnosed multiple myeloma patients are meeting that endpoint — 90 to 99% with one recently-adopted regimen, said Landgren.

Although the overall response rates are high, new drugs are still “absolutely” needed, said Landgren. Meeting the ORR endpoint requires only a 50% reduction in disease, he explained.

“Patients with residual disease will inevitably suffer from relapse and refractoriness,” said. Landgren. “In multiple myeloma, there is an unmet need until we have a cure.”

 

The Need for a New Endpoint

With so many patients meeting the ORR endpoint, showing that a new drug is superior to existing therapies in clinical trials has become increasingly difficult.

To show a statistically meaningful benefit, researchers have to wait for study data to mature on the clinical outcome of progression-free survival, said Dr. Landgren. It could take 10 years or longer for a new drug to clear the bar.

“It is no longer possible to develop new therapies for patients with newly diagnosed multiple myeloma, with ORR in the accelerated approval pathway,” said Dr. Landgren. “There is an urgent need for a new objective early endpoint which can replace ORR.”

Also joining the meeting was Jenny Ahlstrom, a patient advocate who has lived with multiple myeloma since her diagnosis at age 43, 10 years ago.

“Patients are living longer, and that’s a blessing. But it’s also sort of a curse when it comes to clinical trials or drug development because now we have to wait longer to get results, especially for newly diagnosed patients,” said Ahlstrom, who is CEO and founder of the HealthTree Foundation, which provides support to blood cancer patients.

“How do we maintain the pace of innovation?” asked Ahlstrom.

Researchers have long focused on minimal residual disease (MRD) as a newer endpoint.

 

A Focus on Minimal Residual Disease

Techniques that measure MRD can detect tumor cells in the blood or bone marrow with a sensitivity down to one in a million cells, including a DNA-based test cleared by the FDA for the market in 2018. Clinical trials for multiple myeloma now routinely test for MRD, and doctors use the measurement to guide treatment decisions.

MRD is such a sensitive readout of disease that researchers can start to see differences in responses between drug regimens quickly, within months. Studies have shown that MRD negativity correlates with clinical improvements, such as overall survival and progression-free survival.

In 2009, Dr. Landgren helped bring together the FDA, the National Heart, Lung and Blood Institute and the National Cancer Institute, where he was then chief of the Multiple Myeloma Section. The agencies launched an initiative to assess MRD as a measurement of the disease.

Since then, Dr. Landgren and his colleagues have regularly conducted research assessing the link between MRD and clinical outcomes. Last year, they completed the EVIDENCE meta-analysis, assessing more than 1,616 high-quality studies involving more than 8,000 multiple myeloma patients, conducted using criteria pre-approved by the FDA.

The meta-analysis was conducted in collaboration with researchers at other institutions, including Memorial Sloan Kettering Cancer Center, where Dr. Landgren was chief of the Myeloma Service after leaving the NCI and before joining Sylvester. Sloan Kettering associate attending biostatistician Sean Devlin, Ph.D., led the statistical evaluation.

“We have worked relentlessly on this for 15 years, and we have had continuous FDA feedback throughout the process,” said Landgren. “This is a very big undertaking.”

Bolstering their case is a separate analysis led by the International Myeloma Foundation and Mayo Clinic researchers, which was also presented at the FDA meeting, said Landgren.

“The results from these two independent studies are consistent and supportive of each other, which is a major strength,” said Landgren, who joined Sylvester in 2020.

 

Seeking a Cure 

From the start, Landgren’s aim at Sylvester has been to build a world-class program in multiple myeloma. “Our mission is driven by the unmet medical needs of patients diagnosed with myeloma,” said Landgren, who also lead Sylvester’s Experimental Therapeutics Program.

The efforts of he and his colleagues on MRD in multiple myeloma also may help pave the way for regulatory authorities for other blood cancers that use the same measurement, and could have implications for other types of cancers in the longer-term.

“It’s great that we have all these new drugs, but we are not done yet,” said Ahlstrom. “I don’t just want five years more. I want decades more.”

“Today’s ODAC positive vote – 12-0 in favor – for MRD as an early endpoint for accelerated approval of new multiple myeloma drugs is fantastic news for patients diagnosed with multiple myeloma,” said Landgren. “With MRD as a new endpoint, it will give patients access to new therapies much faster! This is exactly what patients need and want.” 

Read more about this on the InventUM Blog and follow @SylvesterCancer on X for the latest news on its research and care.

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