Menlo's Phase 2 skin data disappoints, shares plummet
- Menlo Therapeutics Inc. disclosed the failure of a Phase 2 clinical study of its experimental drug serlopitant for the treatment of pruritus in adults and adolescents with a history of atopic dermatitis, sending shares down more than 75% on April 9.
- The drug not only missed statistical significance on its primary endpoint, but also its secondary objectives — a result at odds with reduced pruritis seen in two prior Phase 2 studies.
- Safety results showed a greater percentage of patients in the high dose arm of serlopitant actually saw increased atopic dermatitis compared to those in the placebo cohort. A higher percent of patients given the low dose of the drug, meanwhile, experienced worsened pruritus versus the rate seen in the placebo group.
Despite two prior mid-stage successes, Menlo's candidate failed to separate from placebo in reducing itch as measured by an average weekly worst-itch numeric rating scale. While the company was quick to point to a numerically greater reduction in itch scores for patients on the drug, the clinical miss sent shares spiraling downward.
In fact, rather than relieve itch caused by atopic dermatitis — the most common type of eczema — treatment with the drug actually led to greater pruritus in 5.6% of patients given the lower dose (versus 5.1% in the placebo arm and 1.9% on the high dose).
Menlo CEO Steve Basta acknowledged the results were disappointing but stressed other studies of the drug in an effort to retain confidence in the candidate's clinical potential.
As a result of the setback, Jeffries investor David Steinberg advised a downgrade from buy to hold of the company's shares. Steinberg also said it was "unlikely" management would continue with the AD indication. Menlo only went public in January.
For the drug's other proposed indications, including pruritus as a result of plaque psoriasis and to treat refractory chronic cough, Steinberg appeared a bit more optimistic while noting the programs' greater risk. Readouts for these indications are due in late 2018 or early 2019 and the fourth quarter of 2018, respectively.
While results from previous Phase 2 trials were indeed generally positive, there were a total of four patients who reported experiencing worsening pruritus in the treatment arms (two in the 0.25 mg group and two in the 1 mg group) compared with one patient reporting pruritus in the placebo arm.
Curiously, in that earlier trial for pruritis, a number of patients in the serlopitant treatment groups at a single trial site had no detectable levels of serlopitant in their blood samples — something the researchers called "a pharmacokinetic anomaly." But the researchers added this anomaly had no effect on the significance or outcome of those studies.
Serlopitant is an neurokinin-1 receptor antagonist originally developed to treat overactive bladder. It is thought that antagonism of this pathway can reduce chronic and intractable itch. For patients refractory to antihistamines and corticosteroids, the pathway may present a promising option. Binding of NK1-R has been shown to be a mediator of sensory nerve signaling, including the itch-scratch reflex, the cough reflex and the vomiting reflex.
- Menlo Therapeutics Inc. Press release