The paucity of therapeutic choices is a reality often acknowledged by the US Food and Drug Administration (FDA) as it reviews applications for new medical products or expansions to approved indications. This is especially true in the case of rare diseases, the majority of which lack any approved treatments. The FDA continues to emphasize the importance of promoting medical product development for rare diseases, including actions taken within the past few months.

“One of the greatest obstacles facing individuals who suffer from rare diseases is the limited treatment options currently available,” said FDA Commissioner Robert M. Califf, MD, in a statement issued in October 2022.¹ The agency announced that it had awarded 19 new grants and two new contracts totaling more than $38 million in funding over the next four years to support clinical trials, natural history studies, and regulatory science tools related to rare diseases. These grants and contracts were funded by the FDA’s Orphan Products Grants Program.² The agency received 33 clinical trial grant applications, of which 11 were chosen to receive funding (more than $25 million) over the four-year period. Seven of the awards fund studies of rare cancers, largely targeting cancers of the brain and peripheral nerves:³

• Phase 2 study of multi-tumor–associated antigen-specific T-cell therapy (MT-401) for the treatment of relapsed/ refractory acute myeloid leukemia (AML) patients following allogeneic stem cell transplant.
• Phase 1/2 study of 177Lu-DOTATATE for the treatment of recurrent/progressive high-grade central nervous system (CNS) tumors and meningiomas that express somatostatin type 2A receptors.
• Phase 2 study of ASTX727 (combination of decitabine and cedazuridine) for the treatment of malignant peripheral nerve sheath tumor.
• Phase 2 study of palbociclib (CDK4/6i) plus INCMGA0012 (PD-1 blockade) for the treatment of well-differentiated or dedifferentiated liposarcoma.
• Phase 2 study of SONALA-001 sonodynamic therapy for the treatment of diffuse intrinsic pontine glioma.
• Phase 2 study of neoantigen-specific adoptive T-cell therapy for the treatment of glioblastoma.
• Phase 1 study of RNA-lipid particle vaccines for the treatment of newly diagnosed glioblastoma.

Among the 43 natural history grant applications received by the FDA, eight were chosen to receive more than $11 million over the next four years.3 Three of the selected natural history studies are related to rare neurodegenerative diseases: 1) a retrospective and prospective study in amyotrophic lateral sclerosis (ALS) of clinic-based multicenter data collection, 2) a prospective study in ataxia telangiectasia, and 3) a prospective study in myotonic dystrophy type 1 to establish biomarkers and clinical endpoints. These studies serve to meet a requirement under Public Law 117-79, the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS),4 signed into law in December 2021, for the FDA to award grants or contracts to public and private entities to cover costs of research on and development of interventions intended to prevent, diagnose, mitigate, treat, or cure ALS and other rare neurodegenerative diseases in adults and children.

The two contracts that received funding are also related to rare neurodegenerative diseases. One contract, co-funded by the US National Institutes of Health (NIH) and the FDA, will study whether a physical assessment of ALS patients, usually performed in a healthcare professional’s office, can be done remotely at home to minimize the patient burden. The second contract is a landscape analysis of patient-preference information studies focused on brain-computer interface (BCI) devices. For this analysis, the FDA is interested in BCI devices that communicate with the brain and provide patients who are no longer able to speak or move with the ability to interact with their families and healthcare professionals.