On March 2, PTC Therapeutics announced that Translarna (ataluren), which is indicated for cystic fibrosis (CF), did not achieve its primary or secondary endpoints in Phase III clinical trials.

Intended to treat CF patients with nonsense mutations in the CFTR gene, PTC’s Translarna is a benzoic acid derivative protein restoration therapy designed to enable the formation of a functioning protein in patients with genetic disorders caused by a nonsense mutation.

Currently, Translarna is licensed in Europe for the treatment of nonsense mutation Duchenne muscular dystrophy in ambulatory patients ages five years and older.

The primary endpoint of lung function for the Phase III CF study was measured by absolute change in percent-predicted FEV1 over 48 weeks from baseline, and the secondary endpoint was measured by the rate of pulmonary exacerbations. The results of the trial revealed that no statistically significant changes were observed in either percent-predicted FEV1 or rate of pulmonary exacerbations compared to placebo. Even though Translarna was generally well tolerated and had a favorable safety profile, lung function was not improved.

From a previous Phase III CF study, PTC extrapolated that aminoglycoside antibiotics, mainly tobramycin, render Translarna ineffective in CF patients. Tobramycin is most commonly used in CF patients as a treatment for Pseudomonas aeruginosa infections.

Since receiving the disappointing results from its Phase III trial for CF, PTC now plans on discontinuing its current clinical development of ataluren for CF, closing ongoing extension studies, and withdrawing its application for marketing authorization towards CF in Europe.

According to research conducted by GlobalData, the failure of this trial brings bad news to approximately 500 CF patients worldwide who currently do not have any CFTR modulator treatment option indicated for their CF mutation type. The two marketed CFTR modulators, Vertex’s Kalydeco (ivacaftor) and Orkambi (lumacaftor + ivacaftor), currently provide treatment for approximately 54.8% of CF patients in the US. Vertex’s ivacaftor + tezacaftor, a CFTR modulator in late stage clinical trials, will cover an additional 36.2% of CF patients in the US if approved and launched. Thus, about 9% of CF patients in the US, including those with nonsense mutations, are left without a modulating therapy, highlighting an important unmet need in the CF space.

While Vertex, Nivalis, Novartis, and Bayer all currently have CFTR-modulator therapies in early-stage clinical trials, these therapies do not target this specific subpopulation of CF patients. As such, GlobalData anticipates that this need will remain unmet through 2025, leaving substantial room for new market entrants in this CF subpopulation.