Filling Out the Roadmap for Faster Drug Approvals

MIAMI, FLORIDA (Dec. 10, 2024) – A new review published in Blood Cancer Discovery outlines a major multiple myeloma research project that supported a key regulatory decision by a U.S. Food and Drug Administration committee. The decision greenlights a new biomarker endpoint, minimal residual disease, for accelerated drug approval in multiple myeloma, and researchers say it could cut a decade off the drug development process.

How that happened is the topic of a new review co-authored by C. Ola Landgren, M.D., Ph.D., director of the Sylvester Myeloma Research Institute at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, and by Sean Devlin, Ph.D., the project’s lead statistician at Memorial Sloan Kettering Cancer Center.

The review outlines how research by Landgren and colleagues led to a recent ruling by an FDA committee that is expected to be incorporated into agency policy. In April 2024, the committee voted 12-0 to allow a clinical trial endpoint called minimal residual disease (MRD) to support accelerated drug approval in multiple myeloma.

The research examined how measurements of MRD, which can detect minute numbers of cancer cells in the body, correlate with clinical outcomes such as overall survival and progression-free survival.

Based on the data, the committee ruled that MRD-negative disease was reasonably likely to predict clinical benefit in multiple myeloma, the second most common blood cancer.

According to the researchers, the new endpoint could cut a decade off the drug development process.

“Drug approval will now happen much faster” for multiple myeloma, said Landgren.

The implications are even broader. Landgren has been approached for advice by leading researchers in other cancer fields who are similarly seeking to use MRD as an endpoint for FDA approval to speed up the pace of innovation.

A Better Endpoint

More than 20 new drugs have been approved for multiple myeloma in the last 20 years. A high proportion of patients now respond to existing therapies and live longer lives.

The flip side of this success is that it’s now difficult to show, based on standard clinical outcomes, that a new experimental therapy is statistically superior. Trials relying on such endpoints require a large number of patients, and data must be collected over many years.

Landgren and his colleagues began addressing this problem more than 10 years ago when they initiated their study assessing MRD as a potential alternative endpoint.

The result was the EVIDENCE meta-analysis, shorthand for “evaluating minimal residual disease as an intermediate clinical endpoint for multiple myeloma.”  The study culled data from more than 12 clinical trials and more than 6,000 patients.

The EVIDENCE study and a separate meta-analysis by another group swayed the FDA committee to accept MRD as an endpoint for accelerated approval, an expedited FDA process tailored to new treatments for serious or life-threatening diseases.

Landgren said the result will be streamlined drug development, clinical testing and regulatory review for multiple myeloma. He said other diseases may be next, but researchers will have to go through the same rigorous process to get the coveted green light from the FDA.

Key Lessons Learned

Landgren offers three pieces of advice for other cancer researchers:

1. Make sure the timing is right for the disease. Existing therapies have to be good enough to yield deep clinical responses. Before the advent of the new multiple myeloma drugs, clinical endpoints were potentially achievable in small studies in short time frames. “If you had tried this 30 years ago, it would be irrelevant for multiple myeloma,” said Landgren.
2. Work closely with regulatory authorities. Understand FDA guidance, rules and requirements, and develop a statistical plan with the agency ahead of conducting the study. Interact with the agency to analyze the data according to their standards.
3. Gather the data from all key sources. Landgren’s team had to gain the trust of biopharma companies to access their data. “It’s a very difficult task, and it’s surrounded by hefty legal barriers,” said Landgren. “You build on relationships and track record.”

Landgren said the committee vote is already beginning to change drug development. Some drug companies have already modified their multiple myeloma protocols to incorporate the MRD endpoint, and others are incentivized to develop improved technologies for measuring MRD.

“There are many new drugs on the horizon for multiple myeloma. It’s an exciting time,” he said. And now, physicians will learn a lot sooner how well these treatments work.

Read more about this drug development decision on the InventUM blog and follow @SylvesterCancer on X for the latest news on cancer research and care.

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Authors: C. Ola Landgren and Sean M. Devlin

Article Title: Minimal Residual Disease as an Early Endpoint for Accelerated Drug Approval in Myeloma: A Roadmap

DOI: 10.1158/2643-3230.BCD-24-0292

Funding and Disclosures: O. Landgren received research funding from National Cancer Institute (NCI)/National Institutes of Health (NIH), US Food and Drug Administration (FDA), Leukemia & Lymphoma Society, Rising Tide Foundation, Memorial Sloan Kettering Cancer Center, Multiple Myeloma Research Foundation (MMRF), International Myeloma Foundation (IMF), Paula and Rodger Riney Foundation, Tow Foundation, Perelman Family Foundation, Myeloma Solutions Fund, Cannon Guzy Family Fund, Amgen, Celgene, Janssen, and Pfizer; has received honoraria for scientific talks/participated in advisory boards for AbbVie, Adaptive, Amgen, Binding Site, Bristol Myers Squibb, Celgene, Cellectis, GSK, Janssen, Juno and Pfizer; and served on Independent Data Monitoring Committees (IDMC) for international randomized trials by Takeda, Merck, Janssen, and Novartis – all of the above are outside the submitted work. S.M. Devlin acknowledges research funding from Janssen and served on IDMC for Miltenyi Biotec.