Summit Therapeutics ($SMMT) has posted top line data on a Phase Ib trial of its Duchenne muscular dystrophy (DMD) drug, SMT C1100. And with the candidate living up to expectations in terms of therapeutic plasma levels, the drugmaker is preparing to advance into an open label Phase II trial.
Oxford, U.K.-based Summit designed the trial to assess the plasma levels of its drug, something that caused it problems in an earlier study. With very few of the participants in the earlier clinical trial hitting the plasma levels Summit thinks are needed for the drug to have an effect, researchers dug into possible causes for the problem. The investigation led Summit to realize that many of the participants in the study were on low-fat diets, a fact it thinks affected the bioavailability of its drug. Summit took steps in the latest trial to control such external influences.
"In the week before the kids even got going in the trial, the parents spoke to a dietician, they moved onto a balanced diet with a mix of carbohydrate, protein and fat and in addition took the glass of milk [at the time of dosing]," Summit CEO Glyn Edwards said on a conference call to discuss the data. "That seems to have shifted the exposure up in all the patients. We have target levels, including not just peak levels but the time of exposure. Six out of the 12 boys reached the levels that we feel comfortable going into a Phase II study with."
Summit has come up with its target levels using data from animal models and human cells to gauge how much drug is needed to increase levels of utrophin, a similar protein to the one people with DMD are unable to produce. "We're pretty confident that these levels are now such that we should expect to see utrophin upregulation and that should lead to a benefit," Edwards said. If Summit is right, it could be the owner of a drug which is more broadly effective than those in development at BioMarin ($BMRN) and Sarepta Therapeutics ($SRPT).
While its rivals are aiming to help people with specific mutations, Summit wants to treat all DMD patients by modulating levels of utrophin. The idea is unproven, though. The Phase Ib trial found no statistical difference in levels of creatine kinase, a biomarker of muscle damage, between the treatment and placebo arms. While Summit will ultimately want to see that its drug is having an effect on such biomarkers, Edwards downplayed the lack of a difference in the 14-day trial, noting that the earliest changes achieved by its DMD rivals in rigorous studies emerged after 10 weeks.
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