ELX-02, Potential Therapy for CF Nonsense Mutations, Named Orphan Drug

ELX-02, an investigational treatment of cystic fibrosis due to nonsense mutations, has been designated an orphan drug by the U.S. Food and Drug Administration (FDA).

This designation is given to treatments with the potential to improve care for rare diseases, defined as those affecting fewer than 200,000 people in the U.S. It qualifies its developer, Eloxx Pharmaceuticals, to benefits that include seven years of marketing exclusivity if approved, and financial incentives like waived fees, and tax credits to advance its development and testing.

“We are pleased to have received orphan drug designation from the FDA for ELX-02 in the U.S.,” Gregory Williams, PhD, CEO of Eloxx, said in a press release.

“Combined with our previous EMA orphan medicinal product designation in Europe, and upon approvals in the U.S. and the E.U., we will be able to … provide treatment options to patients with high unmet medical needs, particularly in patients with nonsense mutations for whom there are few, if any, treatments available,” Williams added.

Cystic fibrosis (CF) is caused by mutations in the gene CFTR, resulting in the production of a faulty CFTR protein.

One type of CF-causing mutation is known as a nonsense mutation. These are mutations that cause a “stop” signal to be coded in the gene, somewhat analogous to having a period erroneously placed in the middle of a sentence. A premature stop codon results in the production of a shortened protein that is unable to work properly.

ELX-02 is designed to restore the production of full-length and functional CFTR protein. The therapy works by binding to ribosomes — the cells’s protein-making machinery — allowing them to “read through” the aberrant stop signal to generate fully working protein.

Phase 1 clinical trials conducted in healthy volunteers showed that ELX-02 was generally well tolerated, and preclinical studies have supported its efficacy.

Eloxx is currently sponsoring two Phase 2 clinical trials — called EL-004 (NCT04126473) and EL-012 (NCT04135495) — to test ELX-02 in people with CF who have at least one G542X mutation in CFTR, the most common CF-causing nonsense mutation.

EL-004, taking place in Germany and Israel, aims to enroll 16 patients; EL-012 is being conducted in the U.S. and plans to enroll eight patients. Enrollment for both trials was nearly complete at the start of the year, but both trials were paused due to the COVID-19 pandemic.

Enrollment in EL-004 recently restarted, while EL-012 remains on hold at its five U.S. sites. Contact and site information about EL-004 can be found here; information about EL-012 is here.

“As previously announced, we have resumed enrollment in our Phase 2 proof of concept clinical trials in Israel and Europe, with our trial in the U.S. continuing to be temporarily paused due to the COVID-19 pandemic,” Williams said. “We look forward to reporting top line results as soon as feasible.”