Three More Experimental Therapies Receive Rare Pediatric Disease Designation by FDA

Rare Daily Staff

The U.S. Food and Drug Administration granted Rare Pediatric Disease designation to three companies for their experimental therapies, just days after handing it out to three other companies.

The new designations cover Imara’s IMR-687 for the treatment of beta-thalassemia; Marinus Pharmaceuticals’ ganaxolone for the treatment of CDKL5 deficiency disorder; and Dynacure’s DYN101 for the treatment of myotubular and centronuclear myopathies.

IMR-687 is a highly selective and potent small molecule inhibitor of PDE9, acting to increase cyclic guanosine monophosphate (cGMP) levels, which are associated with reactivation of fetal hemoglobin. Increased levels of HbF in red blood cells have been demonstrated to improve symptomology and lower disease burden in patients with sickle cell disease and patients with beta-thalassemia, inherited blood disorders that lead to low levels of hemoglobin, impaired blood flow, increased inflammation, greater cell adhesion and reduced nitric oxide mediated vasodilation.

Imara recently initiated a phase 2b clinical trial of IMR-687 in adult patients with beta-thalassemia and expects to dose the first patient in the near-term. Imara anticipates initiating pediatric clinical testing in beta-thalassemia after gathering sufficient clinical data in adult patients with beta-thalassemia.

IMR-687 has also received Fast Track designation, a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need.

Marinus’ ganaxolone is a positive allosteric modulator of GABAA receptors that is being developed in intravenous and oral formulations as an anti-seizure medication. Marinus has conducted the first ever phase 3 pivotal trial in children with CDKL5 deficiency disorder, and is conducting a phase 2 trial in Tuberous Sclerosis Complex, as well as a phase 2 biomarker driven proof of concept trial in PCDH19-related epilepsy.

CDKL5 deficiency disorder (CDD) is a serious and rare genetic disorder that is caused by a mutation of the cyclin‑dependent kinase‑like 5 (CDKL5) gene, located on the X chromosome that encodes proteins essential for normal brain function. It predominantly affects females and is characterized by early‑onset, difficult‑to‑control seizures and severe neuro‑developmental impairment. Most children affected by CDD cannot walk normally, talk, or care for themselves. Many also suffer from scoliosis, visual impairment, gastrointestinal difficulties and sleep disorders. There are no treatments approved specifically for CDD. Genetic testing is available to determine if a patient has a mutation in the CDKL5 gene.

Dynacure’s DYN101 is an experimental antisense medicine, developed using Ionis’ technology, which is designed to modulate the expression of dynamin 2 (DNM2) for the treatment of myotubular and centronuclear myopathies (CNM). CNMs are serious, rare, life-threatening disorders that affect skeletal muscles from birth that are driven by mutations in multiple genes including DNM2. Preclinical studies have demonstrated that DYN101 has the potential to be disease modifying in CNM and Dynacure has begun a phase 1/2 study to evaluate its safety and tolerability, pharmacokinetics, and preliminary efficacy in approximately 18 patients older than 16 years of age with X-linked or autosomal dominant CNM.

The FDA grants Rare Pediatric Disease designation for serious diseases that primarily affect children ages 18 years or younger and fewer than 200,000 persons in the United States. If the FDA approves the experimental therapy, the designation may enable the company to receive a Rare Pediatric Disease Priority Review Voucher program.

The vouchers can be used to reduce the time of an FDA new drug approval review to six months from ten months. The vouchers are potentially lucrative because they are transferable. Most recently, Sarepta sold its priority review voucher to Vifor Pharma $111 million in February 2020.

Editor’s note: This story was updated to correct the most recent sales of a priority review voucher.