May 12 was a big day for advancing rare disease treatment as the FDA granted Orphan Drug Designation to Stealth BioTherapeutics, Neurocrine Biosciences, and Editas Medicine. Stealth BioTherapeutics aims to treat Duchenne muscular dystrophy, Neurocrine Biosciences is focused on chorea associated with Huntington’s disease, and Editas Medicine on beta thalassemia, a rare blood disorder.
Significance of the Orphan Drug Program
The FDA established its Office of Orphan Drug Development program in 1983 to assist in developing treatments for rare diseases and conditions. A rare disease or condition that affects less than 200,000 people in the United States qualifies as a rare disease. Any treatment development targeting one of these diseases is eligible for the Orphan Drug Designation Program.
The perks that come along with an Orphan Drug Designation are tax credits for qualified clinical trials, exemption from user fees, and most notably, the potential for seven years of exclusive marketing rights after approval.
The unique program has assisted in developing over 600 drugs and biologic products aimed at treating rare diseases since its inception. With approximately 7000 rare diseases recognized, the FDA is always looking for opportunities to assist biotech and pharmaceutical companies in researching treatment options for these debilitating and potentially life-threatening diseases.
Stealth BioTherapeutics’ Mitochondrial Motivations
Stealth BioTherapeutics announced that its lead product candidate, elamipretide, received Orphan Drug Designation to develop a treatment for Duchenne muscular dystrophy (DMD). Stealth has also confirmed that it has been granted a pre-Investigational New Drug meeting with the FDA’s Division of Neurology to discuss using elamipretide in combination with phosphorodiamidate morpholino oligomers to treat muscular dystrophy.
DMD is a rare muscle disorder that affects males almost exclusively. Raredisorder.org states that approximately 250,000 are affected by DMD, but Stealth still received Orphan Drug Designation and the associated benefits that come with the designation. DMD is usually detected in early childhood. As the child grows older, muscles in the lower legs, pelvic area, and upper arms develop weakness and atrophy before spreading to the rest of the body. Several health complications are associated with DMD like cardiomyopathy, increased risk of respiratory infections, and dysmotility.
Stealth BioTherapeutics’ elamipretide is a peptide compound that penetrates cell membranes, targets the mitochondrial membranes, and binds to cardiolipin. Stealth stated that preclinical and clinical studies have shown that this mechanism normalizes the inner mitochondrial membrane and improves mitochondrial function. This function is essential to DMD because the rare disease is thought to be associated with mitochondrial dysfunction.
Stealth BioTherapeutics is also studying elamipretide to treat Barth syndrome, geographic atrophy, and primary mitochondrial myopathy due to nDNA mutations.
Neurocrine BioSciences’ Hunt for Huntington’s
Neurocrine BioSciences’ valbenazine (brand name INGREZZA) received Orphan Drug Designation for its potential to treat chorea associated with Huntington’s disease (HD). Chorea is a movement disorder where individuals make involuntary abrupt, irregular, and unpredictable movements. HD and chorea are closely associated because HD is a neurodegenerative disease, and as neurons degenerate, loss of intellectual abilities, emotional disturbances, and uncontrolled movements can occur.
In its Phase 3 clinical study, KINECT-HD, Neurocrine is studying the effect of a daily oral dose of valbenazine on chorea among 128 adult participants. The FDA originally approved valbenazine to Neurocrine BioSciences in 2017 for tardive dyskinesia (TD), a different movement disorder typically affecting the movement of a patient’s mouth and jaw area.
Though valbenazine has proven to reduce uncontrollable body movements associated with TD, INGREZZA states that the mechanism at play is not fully understood. INGREZZA states that a reason it may improve patient outcomes is that movement disorders may be associated with increased dopamine signaling in the brain. Valbenazine may play a role in decreasing that signaling.
Following the KINECT-HD study, Neurocrine is planning the KINECT-HD2 study, which will enroll 150 participants for a 112-week period to study the long-term safety and tolerability of valbenazine for patients with chorea.
Editas Medicine’s Blood Disorder Orphan Drug
Genome editing company Editas Medicine received an Orphan Drug Designation for its investigational medicine, EDIT-301, to treat beta thalassemia. Last month, EDIT-301 received a Rare Pediatric Disease Designation to treat beta thalassemia and sickle cell disease.
Beta thalassemia is a rare blood disorder that affects approximately 1 in 100,000 individuals in the United States and is an inherited blood disorder that results in reduced levels of functional hemoglobin. The severity and symptoms of beta thalassemia vary drastically, but serious cases can be life-threatening due to severe anemia and organ failure.
Editas’ EDIT-301 leverages CRISPR gene-editing technology to increase fetal hemoglobin production. The revolutionary technology has the potential to provide a one-time treatment for patients suffering from beta thalassemia.
As the prevalence of rare diseases rises, medical technology must keep up with the demand to treat patients in need. The FDA’s Orphan Drug Development program is crucial to provide incentives for companies to develop therapies for diseases that may otherwise lack treatment options. These three Orphan Drug Designations are a step forward in offering treatment possibilities for previously unmet medical needs.
