Taiho's late-stage Duchenne candidate fails trial

Taiho Pharmaceutical has suffered a blow to its near-term pipeline after a drug candidate for Duchenne muscular dystrophy (DMD) missed the mark in a phase 3 trial.

The REACH-DMD study of pizuglanstat (TAS-205) – a selective haematopoietic prostaglandin D synthase (HPGDS) inhibitor being developed by Otsuka subsidiary Taiho for the Japanese market – showed no significant difference in the mean change from baseline to 52 weeks in the time to rise from the floor.

That was the primary endpoint in the ambulatory cohort of the study, which has enrolled 82 patients in Japan with DMD aged five years and older and includes both ambulatory (able to walk) and non-ambulatory cohorts. It is comparing a twice-daily oral dose of pizuglanstat to placebo.

Taiho said it would present the results from the study at an upcoming medical conference, but did not comment on the future of pizuglanstat or REACH-DMD. The drug does not appear to have started clinical trials outside Japan.

The result is a disappointment for the DMD community, as pizuglanstat had been held up as a possible treatment for DMD that could be used regardless of the type of dystrophin gene mutation underlying the disease. Targeting HPGDS, which exacerbates the inflammatory response in DMD patients' muscles is a novel treatment approach for the disease.

At the moment, the treatment of DMD relies mainly on infusions of exon-skipping therapies – like Sarepta's Exondys 51 (eteplirsen), Vyondys 53 (golodirsen), and Amondys 45 (casimersen) and Nippon Shinyaku's Viltepso (viltolarsen) – which target specific exons in the dystrophin gene and allow the production of a shorter, but potentially functional, version of the dystrophin protein that is deficient in DMD.

Oral treatment options include Italfarmaco's HDAC inhibitor Duvyzat (givinostat) and Santhera's novel steroid-based therapy Agamree (vamorolone) – both options that can be used regardless of dystrophin mutation – as well as PTC Therapeutics' Translarna (ataluren) which can be used in DMD patients with nonsense mutations.

There is a gene therapy option as well, Sarepta/Roche's Elevidys (delandistrogene moxeparvovec), although that has been hit by patient deaths caused by acute liver failure in non-ambulatory DMD patients, while a cell therapy for DMD cardiomyopathy (deramiocel), developed by Capricor Therapeutics , is due to be scrutinised by an FDA advisory committee later this month.