Aslan Pharmaceuticals is trying to come for Dupixent’s billion-dollar crown in atopic dermatitis, but with mid-stage data showing a more comparable than superior profile, the company hopes less frequent dosing and lower rates of a known side effect may lure patients onto eblasakimab.
The phase 2b dose ranging trial was testing to see if eblasakimab could produce a change in baseline on a rating scale of AD severity called the Eczema Area and Severity Index (EASI) at week 16 compared to placebo. The therapy met the main goal in three of the four dosing arms, which varied a 600 mg, 400 mg or 300 mg dose administered once every four weeks or once every two weeks, according to a Thursday press release.
Eblasakimab performed best in the 600 mg arm dosed every four weeks, with 62.7% of patients achieving an EASI-75 score compared to 30.7% on placebo with a p-value of 0.0041. And 34.1% of patients achieved EASI-90 compared to 10.1% in the placebo arm. This group also saw 31.2% of patients achieve clear or nearly clear skin compared to 15.1% in the placebo arm and 73% of patients had a mean reduction in EASI score from baseline, compared to 51.5% in the placebo group.
The therapy was not successful with a 400 mg dose administered every four weeks, however. This group failed to meet the primary or secondary endpoints, with 51.9% of patients achieving EASI-75 with a p-value of 0.05. Just 24.3% of patients achieved PASI-90 in this dose group, 15% achieved clear or nearly clear skin and 61.9% had a mean reduction in EASI score from baseline.
Shares of Aslan slipped 25% as the markets opened Thursday to $2.87, compared to a previous close of $3.83.
During a conference call with investors, CEO Carl Firth and Chief Medical Officer Alex Kaoukhov, M.D., stressed that eblasakimab outperformed historical trials of Dupixent on EASI-90 achievement in the three groups that did succeed on the primary endpoint. On a 300 mg dose offered every two weeks, 29.7% of patients taking the Sanofi and Regeneron blockbuster hit the EASI-90 mark in a phase 2b study, according to Aslan’s slide presentation, while 32.8% achieved this in a phase 3.
Dupixent is dosed every two or four weeks depending on age and weight via a pre-filled injectable pen after an initial loading dose of two subcutaneous injections.
With 232 patients in the study, Aslan reported 164 treatment-emergent adverse events, but just three were serious. In the 400 mg every four weeks group, eight patients experienced a worsening of their AD. Kaoukhov said these events were deemed not related to the study drug.
“In some patients obviously you see worsening of atopic dermatitis and if it's severe enough it has to be reported as an adverse event,” the CMO said.
Another adverse event of concern is conjunctivitis, which is known to occur in patients taking Dupixent. Firth touted the lower rate of conjunctivitis seen in the eblasakimab trial, which could put Aslan’s offering at an advantage for those prone to the condition. The rate in the study was 5.2% for patients treated with eblasakimab, compared to 1.8% on placebo.
Patients don’t always quit Dupixent due to conjunctivitis, according to Leon Kircik, M.D., a dermatogology professor at the Icahn School of Medicine at Mount Sinai who is a consultant for Aslan. He typically treats the condition by sending the patient to an ophthalmologist and “playing it safe.”
“Usually patients want to stay on the drug; however, if the patient is not clear or is not satisfied, on top of that they're getting the conjunctivitis, then certainly they are looking for another option,” Kircik said.
Aslan would like eblasakimab to be that second option, even as Firth acknowledged the tough job it will be to convince patients to try another medicine.
“We have to bear in mind there are very few other treatment options available and most of these patients are deriving certainly some benefit from [Dupixent]. So it's very challenging for them to consider coming off it,” Firth said. “I think if you present to them an alternative treatment that had comparable—possibly better—efficacy with lower rates of conjunctivitis, a monthly regimen, I think it will be a much easier decision to consider switching away.”
Analysts had questions about the high performance of the placebo arms. Kircik noted that the drug well out-performed placebo on the most important measures: EASI-90 and the clear skin rating scale.
“If the drug gets approved tomorrow, it's gonna be a great gain, not only for the patients but for us as clinicians that we're going to have something new in our armamentarium to treat atopic dermatitis. It's a win-win situation,” Kircik said, noting “very encouraging” efficacy.
He cautioned that dermatology practitioners are “very, very risk averse.” If eblasakimab can bring the adverse event rates down, it could someday become a first-line option. Aslan’s therapy also seemed to kick in quickly, with a sharp decline in severity occurring by the second week.
“We are a very impatient society. Our patients want to get better the next day,” he said.
With the mixed data between the doses, Kaoukhov said the 600 mg dose every four weeks is being considered for the phase 3 trial. Aslan will also be tweaking the inclusion/exclusion criteria for the coming late-stage trial. The CMO said one option is extending the “washout period” between taking a previous medication and entering the trial. However, this could restrict the patient population as many are unwilling to go off therapy for too long.
“Obviously it's a difficult balancing act to keep the studies feasible,” Kaoukhov said. “It's a very difficult disease and keeping patients off of treatment for an extended period of time, it's a difficult proposition to make.”