A Group of Innovative Orphan Drugs Win FDA Approval in 2021

Rare Daily Staff

The U.S. Food and Drug Administration approved 26 novel orphan drugs in 2021, down from 31 novel orphan drugs (58 percent of the novel drug approvals) the previous year. Orphan drugs accounted for 52 percent of the total 50 novel drugs approved by the FDA’s Center for Drug Evaluation and Research in 2021. Just less than half of the approvals were for rare forms of cancer.

Some 21 of those drugs (81 percent) reflected first-in-class approvals, an indication of the strong innovation that is ongoing in the rare disease sector. A total of 22 of the orphan drugs won their first approval in the United States.

In a reflection of the disproportionate benefit rare disease therapies get from various FDA designations, 21 were approved with a Priority Review, 10 of the rare disease drugs won accelerated approval, 16 had Fast Track designations, 15 had Breakthrough Therapy designations. 

Notable approvals in 2021 included PharmaEssentia’s Besremi to treat adults with polycythemia vera, a rare, chronic, and life-threatening blood cancer caused by a mutation in stem cells in the bone marrow, resulting in the overproduction of blood cells. When this occurs, it puts a person at risk for serious health problems, including blood clots, stroke and heart attack. Besremi is the only interferon approved for PV. It is a monopegylated, long-acting interferon that exhibits its cellular effects in polycythemia vera in the bone marrow. Besemri was approved with a boxed warning for risk of serious disorders including aggravation of neuropsychiatric, autoimmune, ischemic, and infectious disorders.  

Two of the approvals in 2021 involved treatments for pruritis, an intense itching, associated with different rare liver diseases. Albireo won approval for Bylvay, the first drug approved for the treatment of pruritus in all subtypes of progressive familial intrahepatic cholestasis (PFIC). PFIC is a disorder that causes progressive liver disease and typically leads to liver failure. Bylvay is a potent, non-systemic ileal bile acid transport inhibitor, which does not require refrigeration and is easily administered as a once-daily capsule or opened and sprinkled onto soft foods. Albireo is launching Bylvay immediately to accelerate availability for the patients and families impacted by PFIC.

The agency also approved Mirum Pharmaceutical’s Livmarli to treat cholestatic pruritus in Alagille syndrome, an inherited condition in which bile builds up in the liver. It is the first and only FDA-approved medication for this rare liver disease which affects 2,000 to 2,500 children in the United States. Livmarli is a minimally absorbed ileal bile acid transporter (IBAT) inhibitor.

Apellis Pharmaceuticals won approval for Empaveli, the first and only C3 targeted therapy to treat adults with paroxysmal nocturnal hemoglobinuria (PNH), a rare, life-threatening blood disease. PNH is caused by an acquired mutation that leads to uncontrolled complement activation and the destruction of red blood cells through intravascular and extravascular hemolysis.

Origin Biosciences won approval for Nulibry, the first therapy approved for molybdenum cofactor deficiency type A, an inherited disorder that typically presents in the first few days of life. The condition causes hard-to-control seizures, brain injury, and death.

Other notable approvals included BioMarin’s Voxzogo to treat achondroplasia, the most common form of dwarfism; and Ascendis Pharma’s Skytrofa for the treatment of pediatric patients one year and older who have growth failure due to inadequate secretion of endogenous growth hormone. Skytrofa offers patients an opportunity for once weekly treatment. Other approved human growth hormones require daily administration.

The FDA’s U.S. Center for Biologics Evaluation and Research approved a total of 13 novel biologics in 2021, five of which carried orphan designations. This included Enzyvant’s regenerative tissue-based therapy Rethymic for immune reconstitution in children born without a thymus. Rethymic (allogeneic processed thymus tissue-agdc) is the first and only treatment approved by the FDA for immune reconstitution in pediatric patients with the ultra-rare condition pediatric congenital athymia. Children with the condition are born without a thymus and have profound immunodeficiency, life-threatening immune dysregulation, and high susceptibility to potentially fatal infections as a result. Rethymic is engineered human thymus tissue designed to regenerate the thymic function children with congenital athymia are missing and does not require donor-recipient matching.

The agency also approved Liminal Biosciences’ Ryplazim the first approved treatment for patients with plasminogen deficiency type 1, also referred to as hypoplasminogenemia, a disorder that can impair normal tissue and organ function and may lead to blindness.