Atopic dermatitis is being pitched as a big new market for immune-modifying drugs but is a tough drug development prospect—as Vanda Pharmaceuticals has just found out.
A phase 2 trial of the biopharma firm's neurokinin-1 receptor tradipitant failed to hit its main target of improving average levels of chronic pruritis (itching) compared to placebo measured via a visual analog scale (VAS). The company said the failure was a result of a high placebo response, a factor which has plagued many trials of therapies for the chronic skin condition.
Vanda is looking on the bright side, saying that tradipitant was able to achieve statistically significant improvements compared to placebo in the intensity of the worst itch experienced by patients measured using VAS, and it reduced the overall severity of disease based on the widely used SCORAD (Scoring Atopic Dermatitis) index, which evaluates swelling, dryness, oozing and skin thickening, among other symptoms.
The SCORAD improvement—which is based on patient assessments—was backed up by a significant improvement in the physician-led Clinical Global Impression (CGI) scale, said Vanda. CEO Mihael Polymeropoulos, M.D., said overall he was "extremely pleased" with the results and that tradipitant's "ability to significantly help the underlying pathophysiology of atopic dermatitis represents a potentially significant medical advance in treating these patients."
That upbeat interpretation wasn't quite enough to calm investors, who reacted to the top-line results by driving the share price down almost 6% in after-hours trading. Moreover, the company said recently that the FDA was not enamored of using VAS as an endpoint, but according to Polymeropoulos has not proffered an alternative.
Analysts at Jefferies said that the company believes the worst itch VAS is more compelling to the FDA than average itch VAS, "offering a regulatory path forward in phase 3 in 2018+."
Atopic dermatitis is notoriously hard to pin down clinically, as it is a diverse disease with a broad range of symptoms driven by a highly complex set of genetic and immunological mechanisms. That has made developing new drugs for the disease challenging, and for years patients could only rely on elderly treatment options such as emollients and topical steroids to manage symptoms.
Last year, Pfizer added to options available with its topical drug Eucrisa (crisaborole) for patients with mild to moderate symptoms. That drug has been tipped to make peak sales of $2 billion thanks to pent-up demand for new and effective treatments. And in March, Sanofi and Regeneron claimed approval for IL-4 and IL-13 inhibitor Dupixent (dupilumab) for patients with moderate-to-severe symptoms, which is also tipped for blockbuster status.
Vanda licensed tradipitant in 2012 from Eli Lilly, which had been developing the drug for treating alcohol dependence, for just $1 million upfront and $99 million in milestone payments.
The company is conducting a second tradipitant study in patients with gastroparesis, but because of slow recruitment it now expects to report results not this year but in in the first half of 2018.