Cystic Fibrosis & Amyloidosis Orphan Drugs Get European Yes

The European Medicines Agency (EMA) recommended in its April meetings approval of marketing authorizations for two orphan medicines: Alyftrek for the treatment of cystic fibrosis and Attrogy for the treatment of hereditary transthyretin (TTR)–mediated amyloidosis.

Alyftrek, a combination of deutivacaftor, tezacaftor, and vanzacaftor, manufactured by Vertex Pharmaceuticals (Ireland), is indicated for the treatment of cystic fibrosis (CF) in people aged 6 years or older who have at least one F508del mutation or another responsive mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

The Committee for Medicinal Products for Human Use (CHMP) said that two active ingredients, vanzacaftor and tezacaftor, are CFTR correctors that bind to different sites on the CFTR protein, leading to an increase in the amount of CFTR protein on the cell surface, while deutivacaftor improves the activity of the defective CFTR protein at the cell surface. These combined actions make lung mucus and digestive juices less thick, thereby helping to relieve CF symptoms. The drug yielded improved lung function, as measured by percent predicted forced expiratory volume in 1 second, after 24 weeks of treatment.

Two phase 3, randomized, double-blind clinical studies in patients with CF and non–class I mutations aged 12 years or older had shown Alyftrek to be as effective as Kaftrio, another triple combination agent (elexacaftor/tezacaftor/ivacaftor) already approved for this patient population.

Alyftrek was designated as an orphan medicine for the treatment of CF in the European Union (EU) in 2021. It is available as film-coated tablets in doses ranging from 4 mg to 125 mg. It is subject to additional monitoring to allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions, the most common of which are nervous system, gastrointestinal, and hepatobiliary disorders; skin rashes; and elevated creatine phosphokinase.

New Agent for Hereditary AmyloidosisThe CHMP also adopted a positive opinion for Attrogy (diflunisal) for the treatment of hereditary TTR–mediated amyloidosis in adult patients with stage I or stage II polyneuropathy. The applicant for marketing authorization was Purpose Pharma International AB.

The condition is characterized by slowly progressing peripheral sensorimotor and/or autonomic neuropathy. Amyloidosis can involve several organs, including the heart, central nervous system, eyes, and kidneys.

The active substance of Attrogy, diflunisal, stabilizes the TTR tetramer, preventing its dissociation into the TTR monomers that are responsible for the disease pathology. The committee said that a randomized, double-blind, placebo-controlled clinical trial had shown the drug to delay disease progression measured by the Neuropathy Impairment Score plus 7 nerve tests (NIS + 7) after 2 years compared with placebo. The most common side effects are gastrointestinal.

Attrogy was given orphan drug designation in 2022. It will be available as 250 mg film-coated tablets.

Detailed recommendations for both products will be given in the summary of product characteristics, which will be published on the EMA website in all official EU languages after the marketing authorization has been granted by the European Commission.