Makary touts FDA speed, flexibility for rare disease drugs

During a meeting to commemorate Rare Disease Day on Monday, officials from the US Food and Drug Administration (FDA) highlighted the importance of collaboration among stakeholders, while FDA Commissioner Marty Makary touted recent FDA initiatives to speed the development of new drugs for rare diseases.

The officials also said the agency is working to incorporate the perspectives of multiple stakeholders – including patient advocates, industry, and physicians – into its policies. For instance, they said FDA is paying close attention to the message that patients and their families are seeking incremental improvements in survival for new treatments of rare diseases, rather than expecting a grand slam.

FDA Commissioner Marty Makary said that while significant progress has been made in addressing rare diseases, further efforts are necessary.

“We live in very exciting times right now, rare diseases were previously underappreciated and underrecognized, but now the FDA has several programs to help advance the cause,” Makary said.

Makary said these efforts include the Orphan Drug Act, tax credits for conducting clinical trials, waiving user fees, expanded access, and the rare pediatric disease priority voucher program.

“Speed is a high priority for all therapies not just rare diseases. Last year we created the National Priority Voucher Program which can accelerate the review [of drugs] from 10 to 12 months to two months,” Makary added. He noted that about a third of the recipients of the voucher program are for rare diseases.

Other initiatives he cited include a set of flexibilities for manufacturing cell and gene therapies, and the agency’s embrace of Bayesian statistics to support optimal dosing for pediatric patients.

The newest initiative is the plausible mechanism framework, a new regulatory pathway for ultra-rare diseases and individualized therapies. The program was announced at a press conference on the same day. (RELATED: FDA proposes plausible mechanism pathway for ultra-rare diseases, Regulatory Focus 23 February 2026)

Makary said that “scientists are now very good at characterizing the molecular changes that underlie a genetic disease and can sometimes help develop therapies designed to target those particular unique circumstances. It is generally not feasible to conduct a randomized clinical trial for this type of therapy, given how rare and specific it is. The plausible mechanism framework is a way of streamlining the path for these types of therapies for patients who are suffering from these ultra rare and bespoke conditions.”

“These [initiatives] are all great but we need to keep going,” Makary said.

Patient engagement initiatives

During the meeting, experts from each FDA medical product center highlighted how patient engagement is driving policy in the rare disease sector, aiming to increase treatment options in this area.

Najat Bouchkouj, associate director for pediatrics and the Office of Therapeutic Products (OTP) at the FDA’s Center for Biologics Evaluation and Research (CBER), stated that under the Prescription Drug User Fee Act (PDUFA VII), the FDA has committed to enhancing patient engagement in the cell and gene therapy space.

As a result, the FDA held two patient listening meetings in 2024, one in September and the other in December. The first meeting focused on safety considerations for approved cell and gene therapies, the second addressed early enrollment in cell and gene therapy clinical trials.

At the meetings, patients expressed the importance of measuring quality of life outcomes, not just focusing on toxicity data. They also emphasized that both patients and caregivers need risk information presented in plain language.

Bouchkouj said that some of these insights have been incorporated into the FDA's regulatory policies. For instance, FDA captured these sentiments in a draft guidance in September 2025 regarding post-approval methods for capturing safety and efficacy data for cell and gene therapy products.

Kristin Wessel, a medical officer in the Division of Oncology 2 at the FDA’s Center for Drug Evaluation and Research (CDER), discussed how the agency is promoting drug development for osteosarcoma by collaborating with patients and advocacy groups.

Wessel noted that since the approval of methotrexate in 1988, no new drugs have received FDA approval for this condition. Currently, the survival rate for patients with metastatic or recurrent osteosarcoma is only 20%.

Wessel added that osteosarcoma makes up 5% of all pediatric cancers, with around 800 new cases diagnosed each year in the United States. There is still a significant unmet medical need for this type of cancer, as the last time the FDA approved a drug specifically for osteosarcoma was in 1988.

Although the survival rate from this disease increased from the 1960s to the 1990s, it has since plateaued. “In light of the continued unmet medical need for new treatments for osteosarcoma, we began discussions with the OSI Foundation.” The Osteosarcoma Institute (OSI) is a non-profit organization founded in 2017 to improve survival rates for osteosarcoma by funding research and clinical trials for this disease.

“We began to brainstorm about how to collaborate and identify some of the barriers to drug development for osteosarcoma and formulate new strategies to overcome some of these barriers. The idea for hosting a workshop arose from the acknowledgment that drug development occurs in an ecosystem and achieving progress in rare cancers involves buy-in and coordination from many different stakeholders.”

Wessel emphasized the importance of gaining support from the pharmaceutical industry conducting clinical trials, patient advocates, philanthropic organizations providing funding, regulators, and patients.

The workshop took place in October 2025. Wessel stated that one of the workshop's goals was to bring together key stakeholders to share their perspectives on the challenges of osteosarcoma treatment and to identify opportunities for advancing the clinical development of therapies through collaboration and communication.

“During the day of the workshop we had the opportunity to hear from patients, and some common themes were raised. Some common themes from patients was the shock that they felt when they got the diagnosis, and the treatment that has not changed in 40 years. While it can result in a cure for some, the toxicity that comes from the treatment significantly impacts the quality of life,” Wessel said.

Other key areas of agreement were the need for more consistent genetic profiling of tumor samples to identify “gentler and more targeted therapies,” and the importance of capturing patient reported outcomes

Another key learning was the importance of equitable access to specialized treatment centers. This finding “sparked a discussion on how we can decentralize trials for osteosarcoma” and whether patients have to travel to the center for all of the lab draws, or whether some of the draws be done locally to remove some of these logistical hardships for patients.

Wessel said that patients and families at the meetings also emphasized the need for treatments that improve overall survival, even if these improvements are incremental.

During the osteosarcoma workshop, a parent of a child with osteosarcoma shared their perspective, stating that “I am not looking for a grand slam, I will take singles and doubles all day if this means that my child will live longer.”

She added that “this puts the onus on academia and industry and FDA to ensure that trials are designed to detect real survival benefits that are meaningful to patients.”

“One theme that kept emerging from these discussions is that thoughtful coordination among all the stakeholders is vital to achieving progress. An example of this that we see on an everyday basis is when a pharmaceutical company conceptualizes a new trial for a new therapy. The industry sponsors may seek input from key opinion leaders and doctors and the osteosarcoma community and from FDA and patient advocates when they select the patient populations they will study … Ideally, these discussions should occur well in advance when initiating a trial to support a marketing application to ensure seamless and effective drug development.”

Wessel said that “we continue to foster multistakeholder engagement and encourage pharmaceutical companies to invite patent advocates and academic investigators to meet with us to discuss their drug development programs.”

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Makary touts FDA speed, flexibility for rare disease drugs

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