Rare Disease Day Celebrated on February 28

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February 28, 2025 marked the annual edition of Rare Disease Day, established in 2008 by the European Organization for Rare Diseases (EURORDIS) (1,2). On leap years, Rare Disease Day has been recognized on February 29, the rarest date on the calendar.

The day’s official website said that more than 70 patient organizations partner with EURORDIS on a yearly basis to help build an international community with the objectives of achieving “equity in social opportunities, healthcare, and access to diagnosis and therapies for people living with a rare disease”—some 300 million people worldwide, according to the site (1).

According to the Rare Disease Day website, a “rare disease” is defined as that which affects fewer than one in 2000 people (1). More than 6000 such diseases are known to exist, 72% of them being genetic in nature.

With February 2025 drawing to a close, positive trial results and regulatory approvals have been reported for numerous rare diseases. The following is a brief and non-exhaustive rundown of the latest developments:

Otoferlin-related hearing loss

While congenital deafness present at birth affects approximately 1.7 in 1000 children born in the United States, a specific condition caused by variations in the otoferlin (OTOF) gene is considered ultra-rare, according to Regeneron (3). That information was part of an announcement that the company’s investigational gene therapy, DB-OTO, showed 72-week progress in speech and development in a first child diagnosed at 10 months of age, and a “notable response” in 10 out of 11 other children enrolled in a Phase I/II study (CHORD) so far. A surgical procedure that administers DB-OTO is similar to that of a cochlear implementation, Regeneron said in a press release, allowing it to be deployed in young infants. DB-OTO has received orphan drug designation from both FDA and the European Medicines Agency, and additional fast track, rare pediatric disease, and regenerative medicine advanced therapy designations from FDA.

Myotonic dystrophy type 1 (DM1)

DM1 affects an estimated one in 8000 people, and there are approximately 40,000 patients in the US, 75,000 in Europe, and 15,000 in Japan (4). That’s according to Boston-based PepGen, which on February 24 announced positive initial results from a Phase I trial (FREEDOM-DM1) of its investigational candidate PGN-EDODM1.

DM1 is a monogenic, autosomal dominant, and progressive disorder primarily affecting skeletal, cardiac, and smooth muscles, as well as the central nervous system. In severe cases, life expectancy may be reduced due to the increased mortality rates that accompany pulmonary and cardiac complications—alongside the customary symptoms of muscle weakness, myotonia, cardiac and respiratory abnormalities, gastrointestinal problems, early cataracts, cognitive or behavioral issues, or fatigue (4).

Cerebrotendinous xanthomatosis (CTX)

CTX is a lipid storage disease caused by a mutation in the CYP27A1 gene. This results in a deficiency of an enzyme that is important insofar as the body’s ability to break down cholesterol in a normal way, exacerbated by the gene mutation causing reduced bile production in the liver. When that happens, atypical cholesterol metabolites are deposited and cause damage in places in the body such as the brain, liver, skin, and tendons. FDA announced on February 21 that it had approved Ctexli (chenodiol), from California-based Mirum Pharmaceuticals, as the first drug authorized by the agency to treat CTX (5). The recommended dosage for chenodiol is 250 milligrams, taken orally three times a day. Prescribing information includes a warning for liver toxicity in all patients, and increased risk of liver damage in patients with pre-existing liver disease or bile duct abnormalities.

Primary biliary cholangitis (PBC)

PBC is defined as a chronic, autoimmune disease of the bile ducts, for which there is no cure. In Europe specifically, it affects approximately 22 out of every 100,000 people. Women are more commonly affected than men, and the disease if left untreated can cause liver disease and ultimately liver failure. Gilead Sciences, of California, said on February 20 that its seladelpar, an oral, peroxisome proliferator-activated receptor (PPAR)-delta agonist, was granted conditional marketing authorization by the European Commission for treatment of PBC, either in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA alone, or as a monotherapy in patients unable to tolerate UDCA (6). (The drug is marketed as Livdelzi in the US.)

The pruritus, or chronic itch, and fatigue that are often symptoms of PBC—related to cholestasis, or impaired bile flow—can be debilitating, and a Phase III trial showed that improvement of pruritus was more pronounced after six months of treatment with seladelpar than with placebo (6).

Tenosynovial giant cell tumor (TGCT)

TGCT is a non-malignant type of tumor that forms within or near joints. It is caused by the dysregulation and subsequent overproduction of the CSF1 gene and, if recurring or left untreated, can damage or degenerate the affected joint and surrounding tissues, leading to the potential of significant disability. On February 14, Ono Pharmaceutical of Osaka, Japan announced that FDA had approved its subsidiary Deciphera Pharmaceuticals’ Romvimza (vimseltinib), a treatment in capsule form for adults with symptomatic TGCT for whom surgical resection would cause potential worsening functional limitation or severe morbidity (7).

Even though Rare Disease Day comes around just once annually, news on treatments for rare diseases is always developing, and is a genre worth following year-round.

References

1. Rare Disease Day. What is Rare Disease Day? rarediseaseday.org (accessed Feb. 27, 2025).
2. EURORDIS. Who We Are. EURORDIS.org (accessed Feb. 27, 2025).
3. Regeneron. Latest DB-OTO Results Demonstrate Clinically Meaningful Hearing Improvements in Nearly All Children with Profound Genetic Hearing Loss in CHORD Trial. Press Release. Feb. 24, 2025.
4. PepGen. PepGen Announces Positive Initial Results, Including Robust Splicing Correction, from Ongoing FREEDOM-DM1 Trial in Patients with DM1. Press Release. Feb. 24, 2025.
5. FDA. FDA Approves First Treatment for Cerebrotendinous Xanthomatosis, a Rare Lipid Storage Disease. Press Release. Feb. 21, 2025.
6. Gilead Sciences. Gilead’s Seladelpar Granted Conditional European Marketing Authorization for the Treatment of Primary Biliary Cholangitis. Press Release. Feb. 20, 2025.
7. Ono Pharmaceutical. U.S. FDA Grants Full Approval of Deciphera’s Romvimza (vimseltinib) for the Treatment of Symptomatic Tenosynovial Giant Cell Tumor (TGCT). Press Release. Feb. 14, 2025.