UPDATE: MoonLake hopes another phase 2 win helps IL-17 drug shine brighter in inflammatory race

MoonLake Immunotherapeutics is hoping to maintain its position as a key player in the race to get an IL-17 inhibitor to market for inflammatory skin conditions courtesy of another phase 2 readout the biotech touted as a success.

The trivalent camelid nanobody, called sonelokimab, was able to induce a statistically significant response in patients with active psoriatic arthritis compared to placebo. A total of 46% of patients who received the 60-mg dose and 47% of those who received the 120-mg dose saw a 50% or greater reduction in signs and symptoms of disease activity at Week 12, hitting the trial’s primary endpoint.

These figures covered patients whose treatment involved an initial induction period, MoonLake pointed out. “As expected, the 60 mg dose without induction did not reach statistical significance, confirming the 60 mg and 120 mg with induction as the potential dose regimens to carry forward into phase 3,” the biotech said in the Nov. 5 release.

Across the 207-patient ARGO trial, sonelokimab also achieved all its secondary endpoints, including a 90% or greater improvement from baseline on the Psoriasis Area and Severity Index score for both doses with induction.

AbbVie’s psoriasis blockbuster Humira was used as an active reference in the trial, and, while the study was not powered for statistical comparison, MoonLake claimed that both doses of sonelokimab “numerically outperformed” the arthritis mainstay on the primary endpoint and all key secondary endpoints. These data “further support the potential for sonelokimab as a future leading therapy,” the biotech argued.

“The high performance of sonelokimab and its favorable safety profile continue to support the potential of using a smaller biologic with albumin-binding capacity to inhibit IL-17A and IL-17F for the treatment of inflammatory diseases,” the Zurich-based company added.

However, on an R&D call this morning to discuss the results, a couple of attendees questioned the high ratio of patients in the placebo group, at 20%, who still reported a 50% reduction in symptoms. Some of the patients in this cohort would be on other background medication that could have caused a response, Chief Scientific Officer Kristien Reich explained on the call.

“If we actually look at those patients ‘on placebo’ that have a response, these eight patients … were on pretty high background doses of methotrexate and some of them were on additional corticosteroids,” he said.

“We think this is explainable; this is something that has been seen in other [psoriatic arthritis] trials,” Reich added. “And it means, again, that the most solid comparisons are to an active reference arm.”

Investors didn't seem convinced, however, sending MoonLake's stock down 30% to around $36 in pre-market trading on Monday morning.

Yesterday’s readout follows a successful phase 2 trial for sonelokimab in another skin condition called hidradenitis suppurativa (HS), which sent the Swiss biotech’s stock rocketing 62% in June to around $50 per share, a region it had remained at—until this morning.

The HS trial in June came just days after Eli Lilly handed over $2.4 billion upfront to acquire Dice Therapeutics in another reminder of why IL-17 remains a hot R&D target at the moment.

MoonLake CEO Jorge Santos da Silva, Ph.D., touted the ARGO readout yesterday as a “landmark milestone” that marked “the first trial in psoriatic arthritis using a nanobody.”

“As with our hidradenitis suppurativa program, the preparation of our phase 3 program in PsA is rapidly advancing and expected timing of end-of-phase 2 regulatory meetings will be announced in due course,” da Silva added in the release.

Jefferies analysts have previously suggested that the failure of Acelyrin’s IL-17A inhibitor izokibep to beat placebo in a phase 2b/3 trial in severe HS in September had opened up a space for sonelokimab.

“Due to this competitive landscape change, we now project [sonelokimab] to reach peak penetration of 35% in the U.S. (from 32.5%) and 15% in the EU (from 12.5%), both in post-TNF HS patients in 2035,” the analysts said in a September note.

Editor's note: This story was updated at 11.20 a.m. ET on Monday, Nov. 6, 2023, to include information from MoonLake's R&D call.