Three potential game changers in rare disease therapies

Developing drugs to treat rare diseases is fraught with challenges; these range from trying to recruit from tiny patient populations to fill much-need clinical trials to the complex reimbursement landscape for these innovative, and often bespoke, therapies.

GlobalData’s Pharmaceutical Technology writer Allie Nawrat looks at three case studies of companies on the verge of having treatments for largely ignored rare diseases approved.

Restoring DNA repair functionality to cells: Rocket’s Fanconi gene therapy

Nawrat Says: “Fanconi anaemia (FA) is a rare paediatric inherited disease caused by a mutation in the FANC genes. Patients with Fanconi experience bone marrow failure as they are unable to create new blood cells.

“Rocket wants to change this situation with its lentiviral vector gene therapy, RP-L102. It is specifically for Fanconi-A, which is the most common form of the disease.

RP-L102 is currently in a global registrational Phase IIA study, which has been efficacious and safe in patients so far. Based on these promising signals, RP-L102 has received all accelerated regulatory tools from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The company is hoping to complete its biologics license applications and marketing authorisation applications (MAA) to the two regulators within the next few years.”

PTC’s localised gene therapy for AADC deficiency

Nawrat says: “Slightly further along the drug approval journey is PTC Therapeutics’ AADC deficiency drug, PTC-AADC, for which the company recently submitted an MAA to the EMA. The company expects full EMA approval towards the end of 2020 and to treat the first patients either in the first or second quarter of 2021.

“AADC deficiency is a rare condition caused by a mutation in the DDC gene, which leads to issues with the AADC enzyme and subsequent reductions in the production of dopamine. Children suffering with AADC deficiency fail to reach neurological and development milestones and have a high risk of death early in life.

“PTC’s MAA for its AADC deficiency gene therapy is based on two clinical trials of 26 patients in total.

PTC’s EMEA and Asia Pacific senior vice-president and general manager Adrian Haigh told GlobalData: “It is certainly not ethical to drill a hole in a patient’s head and inject a virus containing a placebo. Regulators need to be open to novel clinical trial design, particularly in rare diseases where you have ethical problems.”

Amryt’s AP101: The first drug for epidermolysis bullosa?

Nawrat says: “Epidermolysis bullosa (EB) is a group of rare skin conditions caused by genetic mutations in the genes that encode for the proteins of the skin, particularly in collagen VII. There are currently no approved treatments for this condition, however, UK drug company Amryt is hoping to submit authorisation applications to the FDA and EMA by the end of 2021 for its EB drug, AP101.

“AP101 is currently being studied in a Phase III study – Amryt claim this is the biggest global EB trial ever undertaken and has been granted rare paediatric disease designation from the FDA.”