Oxford, UK, - Summit Therapeutics plc, the drug discovery and development company advancing therapies for Duchenne muscular dystrophy ('DMD') and Clostridium difficile infection, today reports Phase 1 clinical trial results that show a new formulation of ezutromid (referred to as 'F6') achieved a greater than six-fold increase in maximum plasma levels in DMD patients compared to those achieved with the current clinical formulation (referred to as 'F3') with only two fifths of the dose.
Following these positive data, Summit also outlines its development strategy through to applications for market approval for ezutromid, a utrophin modulator. Utrophin modulation is a potential disease modifying treatment for all patients with this fatal muscle wasting disease, regardless of their underlying dystrophin gene mutation.
"The rigorous development of ezutromid has identified this new F6 formulation that achieved higher ezutromid plasma levels in patients in this trial allowing us to further explore the therapeutic effect of this promising treatment," commented Dr Ralf Rosskamp, Chief Medical Officer of Summit. "Following these encouraging Phase 1 data, we plan to incorporate the F6 formulation of ezutromid into our ongoing Phase 2 trial, PhaseOut DMD. This will allow us to directly compare the safety and efficacy of the F6 and F3 formulations of ezutromid, and help determine which to use in future clinical trials."
"Utrophin modulation focusses on maintaining expression of utrophin protein to protect muscle health and function and we believe these two formulations of ezutromid are capable of achieving this. It is therefore appropriate to now outline our clinical pathway to seek marketing approval of ezutromid."
Informed by these clinical findings, the development strategy includes:
The incorporation of formulation F6 into the ongoing PhaseOut DMD Phase 2 proof of concept trial (subject to regulatory approval). It is planned to evaluate F6 in up to 10 of the 40 patients expected to be enrolled and compare F6 alongside the F3 formulation when dosed longer-term. Initial F3 24-week biopsy data are now expected Q2/Q3 2017.
- A randomised, placebo controlled trial designed with the potential to support accelerated and conditional regulatory approvals in the US and EU respectively; this trial is expected to start in H2 2017 (assuming positive interim data from PhaseOut DMD), with data available for potential regulatory filings in 2019.
"Building on the clinical progress achieved to date, we are pleased to outline our strategy for the development of ezutromid towards possible commercialisation," said Glyn Edwards, Chief Executive Officer of Summit. "These plans focus on efficient evaluation of the efficacy and safety of this utrophin modulator as we work towards making it available to all patients with DMD. Our plans are designed to support early submissions for accelerated and conditional approvals while continuing to build a broad and robust body of clinical evidence for this potentially life-changing treatment."
Results of Phase 1 Clinical Trial of Ezutromid F6 Formulation The clinical data being reported are from the second part of a Phase 1 clinical trial to assess the pharmacokinetics and safety of three fixed doses (250 mg, 500 mg and 1,000 mg twice daily) of the F6 formulation of ezutromid in patients with DMD aged between 5 and 9 years who followed a modified diet. Ezutromid was generally well-tolerated across the doses tested. One patient had changes in liver parameters in laboratory findings; he showed no clinical symptoms but was withdrawn from the trial and the finding was classed as a serious adverse event. At the highest dose, the five evaluable patients achieved an average maximum plasma concentration of 390 ng/mL on day 7, the final day of dosing. Utrophin modulation is also expected with the F3 formulation that in an earlier Phase 1 trial in patients who followed the same modified diet achieved an average maximum plasma concentration of 63 ng/mL (2,500 mg dose, twice daily) on the final day of dosing (day 14). More detailed findings from this Phase 1 trial will be reported at future meetings.