Today, Summit Therapeutics plc announced positive results from a Phase 1 trial of a new formulation of ezutromid, which they are calling F6. In this trial, Summit showed that F6 is able to be better absorbed in patients than the current formulation of ezutromid, which they are calling F3. Because of these positive results, Summit plans to incorporate F6 into its PhaseOut DMD clinical trial alongside F3. This allows Summit to study the effect of higher concentrations of ezutromid with F6 and evaluate how its safety and efficacy compare with the F3 formulation over the 48 weeks of dosing.
Below are some questions that you might have about this announcement provided by Summit, as well as the press release.
1. What is different about this new formulation? Is it still taken orally?
The new F6 formulation of ezutromid uses different technology that helps it to be better absorbed as shown in this Phase 1 clinical trial. At the core, it is still the same drug candidate as the current F3 formulation, and it is still taken orally.
2. Does the new formulation still require a balanced diet and a small glass of full fat milk?
The results from this F6 formulation clinical trial were from patients who followed specific dietary guidance providing for a balanced proportion of fats, proteins and carbohydrates and who took the F6 formulation with a small glass of full fat milk.
3. Is the F6 formulation going to be used in the PhaseOut DMD trial?
We expect that up to ten boys in PhaseOut DMD will receive the F6 formulation of ezutromid, subject to regulatory approval. We are now enrolling up to 30 patients on the F3 formulation.
4. Why aren’t all boys in PhaseOut DMD receiving the F6 formulation?
We believe utrophin modulation will be possible with both the F3 and F6 formulations. The new F6 formulation allows us to study the effect of higher concentrations of ezutromid and evaluate how its safety and efficacy compare with the F3 formulation over the 48 weeks of dosing. We expect the F6 formulation will only be available in the US at a limited number of sites, subject to regulatory approval. We expect the results from PhaseOut DMD to inform which formulation of ezutromid we use in future trials.
5. Is the F6 formulation safe?
The F6 formulation of ezutromid was generally well-tolerated at the doses tested. One patient had changes in liver parameters in laboratory findings; he showed no clinical symptoms but was withdrawn from the trial as a precaution and the finding was classed as a serious adverse event. The enzyme levels returned to normal soon after ezutromid dosing was stopped.
6. Will my son have a better chance of seeing benefit if he’s on the F6 formulation?
We don’t yet know if either the F3 or F6 formulation of ezutromid will produce a clinical benefit in patients with DMD, which is why we are testing both in the PhaseOut DMD clinical trial. The key to beneficial effects of utrophin modulation in animal models of DMD is sustained utrophin production and not necessarily the level of utrophin. We believe both formulations will be able to sustain utrophin production in patients.
7. How will you choose which boys get the F6 formulation?
If the protocol amendment to include the F6 formulation in PhaseOut DMD is approved by the regulatory authorities, we expect to enroll up to ten patients on the F6 formulation. This is likely to occur after 30 patients are enrolled on the F3 formulation, and the assignment of the boys to the F6 formulation will be based on the revised protocol.
8. If the trial is extended, which formulation will the boys receive?
This decision will be based on the data gathered from PhaseOut DMD.
9. If my son is already enrolled in the trial, can I ask for him to go on the F6 formulation?
No, patients who are already receiving ezutromid will continue to get the formulation with which they started. The incorporation of the F6 formulation into the PhaseOut DMD trial will be based on the revised trial protocol, once the amendment is approved by the regulators, and not family/patient/physician choice.
SUMMIT REPORTS POSITIVE PHASE 1 NEW FORMULATION DATA AND OUTLINES ROUTE TO MARKET STRATEGY FOR DMD CANDIDATE EZUTROMID
- New formulation of ezutromid achieved over a six-fold increase in maximum plasma levels in patients
- Plans include incorporating new formulation into PhaseOut DMD trial
Oxford, UK, 9 August 2016 – Summit Therapeutics plc (NASDAQ: SMMT, AIM: SUMM), 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.”