Summit Therapeutics said today it will take as-yet-unspecified measures to cut costs and halt development of its Duchenne muscular dystrophy (DMD) candidate ezutromid after it failed a Phase II trial—triggering a stock selloff that caused shares to lose 80% of their value.
Shares fell to £38.50 ($50.65) from yesterday’s close of £159.00 ($209.20) on the London Stock Exchange in trading as of 1:30 p.m. BST (8:30 a.m.), after the company announced that ezutromid missed its primary and secondary endpoints in the Phase II PhaseOut DMD trial (NCT02858362) after 48 weeks of treatment in DMD patients.
The open-label study was designed to assess the activity and safety of utrophin modulation with ezutromid in 40 boys with DMD ages 5 to 10. Ezutromid was dosed twice a day at either 1000 mg (F6 formulation) or 2500 mg (F3 formulation) at multiple centers in the U.S. and the U.K. PhaseOut DMD included a screening and baseline phase of up to 28 days, a 48-week open-label treatment phase, and a 30-day safety follow-up phase.
The primary endpoint was the change from baseline in magnetic resonance parameters related to the leg muscles, Summit said. Biopsy measures evaluating utrophin and muscle damage were included as secondary endpoints, with patients having two biopsies: one at baseline and their second after either 24 weeks or 48 weeks of ezutromid treatment. Exploratory endpoints included the six-minute walk distance, the North Star Ambulatory Assessment, and patient-reported outcomes.
While statistical decreases in developmental myosin and magnetic resonance T2 measures were seen after 24 weeks of treatment, these effects were not seen after 48 weeks of treatment, Summit acknowledged, without disclosing details.
“These data come as a great disappointment to us and to all those living with DMD,” Summit CEO Glyn Edwards said in a statement.
Ezutromid, formerly SMT C1100, was Summit’s lead utrophin modulator candidate designed to stimulate utrophin production in people who lack dystrophin, such as people with DMD.
Summit said it is working with investigators in PhaseOut DMD to conclude the trial and an associated extension phase, and is exploring how data gathered through the failed trial can be made available to support other DMD research activities for the benefit of the DMD community.
Refocusing on Antibiotics
“While we believe utrophin modulation could still have a place in the treatment of DMD, it is clear that ezutromid is not providing a benefit for patients,” Edwards added. “We therefore feel that our resources are better focused on the development of our promising pipeline of new mechanism antibiotics.”
Summit said its clinical focus has shifted to the infectious disease caused by Clostridium difficile bacteria—for which the company is developing ridinilazole (formerly SMT19969), an antibiotic that is being developed to treat the initial infection and reduce rates of recurrent disease. Ridinilazole has demonstrated clinical proof of concept in a Phase II clinical trial and is expected to enter global Phase III trials in Q1 2019, under a development program for which Summit won a contract for up to $62 million from the Biomedical Advanced Research and Development Authority (BARDA) in September 2017.
Summit is also developing new antibiotics using its Discuva Platform, which combines transposon technology with bioinformatics to create a tool designed to identify new antibacterial drug targets, elucidate antibiotic mechanisms of action, and optimize against bacterial resistance to generate new antibiotic drug candidates.
Earlier this month Summit unveiled its second of two novel targets for the killing of the bacteria Neisseria gonorrhoeae at the ASM Microbe 2018 congress, held June 20–24 in Atlanta, where the company also reported preclinical data on its lead series of “new mechanism” antibiotic candidates for the treatment of gonorrhea, saying it intended to select a candidate to enter Investigational New Drug (IND)-enabling studies in the second half of this year.
The failure of ezutromid comes a week after Sarepta Therapeutics reported positive preliminary clinical data on another DMD candidate.
Sarepta announced that all three patients in the Phase I/IIa gene therapy clinical trial assessing AAVrh74.MHCK7.micro-Dystrophin in patients with DMD showed robust micro-dystrophin expression in muscle measured by all methods, as well as significant decreases in the levels of serum creatine kinase (CK), an enzyme biomarker strongly associated with muscle damage caused by DMD. The mean reduction of CK was over 87% at day 60.
In 2016, Sarepta acquired rights to the pipeline of Summit Therapeutics, led by ezutromid, for Europe, Turkey, and the Commonwealth of Independent States, for up to $562 million-plus.