On $MLTX ... foreseeing today's Ph3 failure.
My stories are published behind STAT's paywall, but for those who are not subscribers, I've written critically / skeptically about sonelokimab going back two years.
Here is what I wrote in June 2023:
https://t.co/hYwsI5xRMO
For two days starting on Sunday, Moonlake Immunotherapeutics happily crunched numbers and shared results from a mid-stage clinical trial that depicted its experimental antibody in the most flattering terms possible.
The drug, called sonelokimab, was “changing the game” for the treatment of a debilitating skin condition called hidradenitis suppurativa, or HS, said Moonlake CEO Jorge Santos da Silva, on a call for investors and analysts. The drug’s benefit for patients placed it “at the top of the heap,” he added.
For other, equally important data from the same study that did not fit Moonlake’s home-run narrative, the company took a DIY approach. Curious about how sonelokimab performed against a treatment that’s already approved for HS? Pull out a calculator and do the math yourself. How badly did a higher dose of the drug underperform a lower dose? Take a guess.
No rule requires biotech companies to be fully transparent with study results, and investors expect management teams to shade discussions of data in ways that accentuate the positives. But Moonlake did a lot more than just brush aside potentially troubling findings. The company worked hard to keep that information from surfacing.
Why? Perhaps to help raise money. Moonlake’s strategy worked. On Monday, the stock rose 78% to $46. On Tuesday, shares rose another 13% to $52. The company floated a $250 million stock offering, which was upsized to $400 million and priced at $50, the company said Wednesday.
Is sonelokimab a blockbuster drug in the making and a “best in class” treatment for hidradenitis suppurativa? It’s entirely possible, as the market reaction suggests. The data not shared freely by Moonlake also raise meaningful doubts.
In its Phase 2 study, 43% of patients treated with a 120 mg dose of sonelokimab showed a 75% reduction in abscesses and inflamed skin nodules that characterize HS. The corresponding response rate in the placebo group was 15%. The result achieved the study’s primary goal, but was also not much of a surprise.
But Moonlake also tested a higher, 240 mg dose of sonelokimab that also beat placebo, but performed worse than the lower dose. Moonlake didn’t disclose the exact response rate, making investors guess based on a line on a chart. The lack of a dose response is typically a warning sign, particularly for antibodies where blocking more of the inflammatory target — in this case a cytokine called IL-17 — should result in greater symptomatic improvement.
Moonlake said the 120 mg dose was an “optimum level” of sonelokimab, so don’t worry about the higher dose proving less effective.
The same study also randomized a group of participants to receive Humira (or adalimumab), which is currently the only approved antibody treatment for HS. Moonlake predicted with confidence that sonelokimab would demonstrate superiority over Humira. Investors expected it.
But when Moonlake announced the study results in a press release on Sunday, the sonelokimab versus Humira comparison wasn’t disclosed. On Monday’s conference call, management only addressed the issue in the most opaque terms. I got the same treatment when I reached out to a company spokesperson for answers to questions about the study.
Sonelokimab beat Humira, the company insisted, but refused to offer specifics. Charts and tables from the study compared the sonelokimab and placebo response rates, but the comparable — and highly relevant — Humira response rates weren’t included.
Some relatively easy calculations explained Moonlake’s behavior: Approximately 36% of participants treated with Humira showed a 75% improvement in their HS symptoms. When that DIY result is overlaid on the data Moonlake chose to disclose, Humira actually beat the higher 240 mg dose of sonelokimab. The lower dose of sonelokimab performed better than Humira, but by a margin smaller than Moonlake expected.
Moonlake has a Humira problem. It has sold investors on the idea sonelokimab is the best treatment for HS. Its own data don’t fully support the claim. The company plans to start Phase 3 studies next year, but comparing sonelokimab against Humira (to show superiority) now looks like a riskier endeavor than it anticipated.
Soon, Humira likely won’t be the only treatment for HS. Bimzelx and Cosentyx are currently approved antibody treatments for other autoimmune diseases, marketed by UCB and Novartis, respectively. Both drugs are likely to secure expanded labels covering HS relatively soon, based on successful Phase 3 studies.
Bimzelx and Cosentyx both work by blocking the inflammatory IL-17 cytokine, just like sonelokimab. That makes it harder for Moonlake to include a placebo arm in its Phase 3 studies because people with HS might balk at the prospect of receiving dummy injections when other anti-IL-17 treatments are approved and available.
Phase 2 studies, even when randomized, tend to produce the best results. Sonelokimab will probably never look better than it did this week. I tip my cap in respect to Moonlake — a little cynically — for stage managing a data presentation that resulted in a $400 million windfall.
The company now has the money it needs to pay for the Phase 3 studies. If drug development history is a guide, the gloss applied to sonelokimab will wear off.
