Sonelokimab

MoonLake Immunotherapeutics’ one and only pipeline drug has generated both a hit and a miss in paired pivotal trials testing it in the painful skin disorder hidradenitis suppurativa. Expectations had been high for the drug, called sonelokimab, with investors hoping that an unequivocal win could lead to a lucrative partnership or an M&A deal. MoonLake’s stock $MLTX dropped around 85% premarket on Monday. Data released Sunday showed that sonelokimab, a nanobody that inhibits IL-17A/F, missed MoonLake’s stated expectations and also fell short of UCB’s established hidradenitis suppurativa therapy Bimzelx on a cross-trial basis. In the VELA-1 trial, 34.8% of patients taking sonelokimab hit a bar called HS clinical response (HiSCR) 75 after four months’ treatment. HiSCR75 represents a 75% reduction in the number of abscesses and inflammatory nodules that characterize the disease. In the trial’s placebo arm, 17.5% met this goal, and the difference was statistically significant. However, the HiSCR75 rate with sonelokimab in VELA-2 was 35.9%, versus 25.6% with placebo. Using a strict statistical analysis that controlled for multiple testing, the delta over placebo was just 9%. That trial did not hit statistical significance (p=0.053). MoonLake said the placebo response in VELA-2 was “higher than expected.” Leerink analysts wrote that the placebo-adjusted figures came in well below MoonLake’s expectations of at least 20%. The identical studies evaluated a 120 mg subcutaneous dose of MoonLake’s nanobody every two weeks for the first six weeks, and once a month starting at week eight. The trials enrolled a total of 838 patients with moderate-to-severe HS. When the data from the two trials were combined, sonelokimab was statistically significantly better than placebo, with a 13.8 percentage point difference over the control arm. But analysts from Stifel called the pooled data “less than competitive.” That’s short of what UCB’s drug achieved in its two trials. In those, Bimzelx achieved a margin over placebo of 15 and 20 percentage points on the four-month HiSCR75 measure, though they used a different statistical analysis. Bimzelx is also an IL-17A/F inhibitor and is a blockbuster thanks to its approval in several indications, including psoriasis as well as HS. Sonelokimab’s safety readout was clean, with 2.9% of patients on the drug discontinuing treatment across both studies because of side effects. That rate was around twice as high as with placebo. MoonLake said it would submit the data to regulators and discuss a path to approval. But the drug’s potential market looks slimmer. So do the chances of MoonLake scoring a deal with a partner or buyer. This summer, Merck was rumored to be interested in buying the biotech. Some had predicted the weak results: Stifel analysts wrote in September that the drug had “limited differentiation versus other IL-17s and an uncertain near-term regulatory path in HS.” They lowered their potential of success for the product from 75% to 33%.

Dive Brief:An experimental immune disease drug from Moonlake Immunotherapeutics fell short of investors expectations in a pair of closely watched clinical trials, sending shares of the Swiss biotechnology company falling more than 80% on Monday.Both late-stage trials focused on patients with a chronic inflammatory skin condition known as hidradenitis suppurativa. In one, about 35% of participants treated with the Moonlake's drug, sonelokimab, had a significant reduction in disease symptoms after four months, versus about 18% of placebo recipients. While that result met statistical significance, the difference between the two groups wasnt as large as executives and investors had hoped.Sonelokimab also failed to meet its main objective in the second study, a result the company blamed on a higher than expected placebo response in a statement Sunday. Moonlake aims to discuss the approval path with regulators while the trials continue but, following the results, multiple Wall Street analysts expressed skepticism about a quick clearance as well as the drugs sales potential.Dive Insight:Moonlake had been hoping the study results would prove its medicine is a step forward in treatment for hidradenaitis suppurativa a skin disease that causes painful abscesses and tissue scarring, and that analysts see as a still-untapped opportunity for drugmakers.Sonelokimab binds to two inflammatory cytokines as well as a third protein, albumin, that are involved in the diseases progression. Moonlake has said the way in which the drug gets at those targets, as well as its small molecular size, might help it be more potent and longer lasting than available biologics like AbbVies Humira, UCBs Bimzelx and Novartis Cosentyx.Data leading up to late-stage testing suggested Moonlakes drug had an optimal profile compared to so-called IL-17 inhibitors like Bimzelx and Cosentyx, Leerink Partners analysts wrote in a January report. Moonlake reportedly turned down a buyout offer from Merck & Co. this year, too.Yet sonelokimab didnt demonstrate the kind of clear-cut dose response in mid-stage testing that investors like to see. In the meantime, the 2023 and 2024 approvals of Cosentyx and Bimzelx, respectively, added pressure for the company not just top its placebo comparator in testing, but show sonelokimab might be competitive with, or even superior to those medicines as well.The results disclosed Sunday, described by analysts as disappointing and undifferentiated, all but erased those hopes. The magnitude of the effects observed looks uncompetitive with Bimzelx, likely relegating sonelokimab to a much narrower role while casting doubts on its potential against other diseases, wrote RBC Capital Markets analyst Brian Abrahams.The data have also introduced uncertainty around Moonlakes approval path and commercial outlook, added Leerinks Thomas Smith.In its statement, Moonlake noted how pooled results from both studies demonstrated a clinically meaningful and statistically significant improvement across all trial goals and how, in the test that failed, placebo recipients responded at a much higher rate than history suggested they would. Executives will discuss the results with regulators, including the analytical strategies now necessary given the placebo groups performance.However, a clear path to approval is likely off-the-table in the near term, wrote Stifel analyst Alex Thompson.Moonlakes share price plummeted from about $62 apiece to less than $10 early Monday. '