A phase 2 trial of Avalo Therapeutics’ hidradenitis suppurativa (HS) candidate hit its primary endpoint, emboldening the biotech to advance toward a registrational study.
While the placebo-adjusted result fell short of the bar set by Avalo, analysts and AbbVie’s rival program, the biotech’s stock jumped in premarket trading.
Investigators randomized 253 adults with moderate-to-severe HS, an inflammatory skin disease, to take one of two doses of the anti-IL-1β antibody abdakibart or placebo. Like AbbVie’s 1α/1β antagonist lutikizumab, which is in phase 3, the former Eli Lilly asset abdakibart is designed to improve outcomes by neutralizing the activity of a pro-inflammatory cytokine implicated in the disease.
Patients in the abdakibart cohorts received either a 600 mg loading dose followed by 300 mg every four weeks, or a 300 mg loading dose followed by 150 mg every two weeks. The primary endpoint looked at HiSCR75, a measure based on a 75% reduction in total abscess and inflammatory nodule count.
At Week 16, the HiSCR75 response rate was 42.2% for the 150 mg dose and 42.9% for the 300 mg dose. The placebo-adjusted response rate was 16.9% for the average of the two abdakibart doses, compared to 21% in the weekly dosing cohort of AbbVie’s phase 2 trial. Cross-trial comparisons can be unreliable, but Avalo’s placebo-adjusted HiSCR75 response rate also fell short of other yardsticks.
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At a TD Cowen event in March, Avalo CEO Garry Neil, M.D., said the biotech expected that “anything over 20% placebo subtracted would be a clear win for the drug, even though we are hoping, and I think we have a reasonable expectation of doing, better than that.” Neil said a 25% placebo-adjusted result would be “a home run” and discussed a “grand slam” scenario in which abdakibart delivered even stronger data.
Guggenheim Securities analysts outlined similar expectations in a note to investors in April. The analysts said a 20% placebo-adjusted response rate would be “a competitive outcome,” although they added that a result over 18% “should be well-received by the Street” given the novel biology.
Yet Avalo’s share price rose 40% to $22.80 in premarket trading Wednesday following news of its 16.9% placebo-adjusted response rate.
Avalo’s inability to hit its 20% target reflected a higher-than-expected placebo response rate. Abdakibart achieved a higher HiSCR75 rate than lutikizumab, with AbbVie reporting responses in 38.5% of patients who received the weekly regimen the Big Pharma took into its pivotal trial. However, Avalo’s placebo response rate, 25.6%, was higher than AbbVie’s 17.5%.
Placebo response rates typically fall in the 13% to 18% range, Neil said in March. However, the Avalo CEO highlighted “a couple of highly visible and notable exceptions lately, especially Vela-2,” referring to the MoonLake Immunotherapeutics’ HS trial that missed its primary endpoint last year. MoonLake reported a 25.6% HiSCR75 response rate in Vela-2.
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The size of Avalo’s trial helped the biotech deliver a statistically significant result despite the placebo response rate. Avalo assumed a 20% placebo response rate when it designed the trial, Neil said at a TD Cowen event in November. Increasing enrollment from 180 to 222 gave Avalo the power to withstand a 22% placebo rate, Neil said, and surpassing that target offered protection against “a placebo surprise.”
Avalo plans to move into phase 3 on the strength of the data. The biotech filed to raise $375 million in a stock offering to secure enough money to deliver topline phase 3 data on the drug candidate in HS.
