In the high-stakes world of biopharma, few stories are as compelling as the race to develop a successor to a multi-billion-dollar drug. We’re joined today by Ivan Kairatov, a biopharma expert with deep experience in research, development, and the intricate dance between clinical data and commercial reality. We’ll be discussing the recent mixed trial results for Sanofi’s amlitelimab, a promising new treatment for eczema. Our conversation will explore the complexities of navigating divergent global regulatory standards, the commercial impact of a single serious adverse event, the immense pressure of succeeding a blockbuster like Dupixent, and what it will take for this new class of drugs to regain market confidence.
A new drug might meet U.S. filing criteria but miss a key European statistical threshold due to different data analyses. How does this kind of mixed result impact a global launch strategy, and what specific steps would a company take to navigate these divergent regulatory landscapes?
This is a classic, and frankly, gut-wrenching scenario that can make or break a drug’s global potential. You have this moment of celebration in one region, but a significant roadblock in another. The immediate impact is a fractured launch strategy. Instead of a unified global rollout, you’re forced into a staggered, resource-intensive approach. A company like Sanofi will pivot to what they call a “totality of the data” argument. This means they won’t just submit the problematic COAST 2 trial data in isolation. They’ll build a comprehensive narrative for the European regulators, leading with the strong, unequivocal success of the SHORE trial and supplementing it with all other positive signals, such as the long-term safety study showing efficacy builds over time. They might also proactively propose post-approval registries or real-world evidence studies to gather more data and reassure regulators. It’s about demonstrating that the one statistical miss—where 28% of patients responded versus 19% on placebo—is an anomaly in an otherwise consistent and positive data package.
When a single case of a serious adverse event, such as Kaposi’s sarcoma, emerges in a late-stage trial, how do regulators typically weigh this risk? Please walk me through the potential commercial impact of a “black box” warning on a new drug’s market adoption by physicians.
Regulators face a difficult balancing act. A single case of a serious cancer like Kaposi’s sarcoma is alarming, and they will scrutinize it intensely. They’ll dig into the patient’s history, comorbidities, and any other potential confounding factors. However, they weigh this one event against the drug’s benefit for a large population suffering from a chronic, often debilitating condition. The key question is whether this is an isolated incident or a signal of a broader risk. Commercially, the fallout can be significant. If the FDA decides the risk is plausible, they can mandate a “black box” warning—the most serious type. This is a literal black box on the drug’s label that screams “caution” to every prescribing physician. It immediately puts the drug at a disadvantage, especially against established treatments like Dupixent that have a clean safety profile. Doctors become hesitant, especially for a less-frequently dosed convenience drug. It could relegate the drug to a second or third-line therapy, dramatically shrinking its potential market share from day one.
Sanofi’s Dupixent is a multi-billion dollar drug with a patent expiring in 2031. Considering amlitelimab’s potential for less frequent dosing but mixed trial data, what key clinical and commercial metrics must it achieve to be considered a worthy successor in a competitive market?
To be a worthy successor to a juggernaut like Dupixent, which pulls in over $13 billion annually, amlitelimab has to clear some very high bars. Clinically, the convenience of a 12-week dosing schedule is its main selling point, but that convenience cannot come at the cost of efficacy or safety. The data must eventually show it’s at least as good as, if not better than, Dupixent in clearing skin lesions for a significant portion of patients. Anything less, and physicians will stick with the devil they know. Commercially, the key metric will be market access and pricing. It needs to secure favorable formulary placement with insurers, and that will be tough if there’s a black box warning or lingering questions about its European approval. To truly succeed, it needs to capture a significant share of new patients and, critically, convince a portion of the vast Dupixent patient pool to switch—a monumental task unless the overall value proposition is overwhelmingly superior.
Market expectations for OX40L inhibitors have cooled after some disappointing data in the class. Given this context, what specific evidence from amlitelimab’s two upcoming Phase 3 trials would be needed to rebuild confidence and truly differentiate it from both Dupixent and other pipeline competitors?
Confidence in the entire OX40L class is fragile right now, so these next two readouts are pivotal. To turn the tide, the data needs to be clean, consistent, and compelling. First, both trials must unequivocally meet their primary endpoints under both U.S. and European statistical models. There can be no more ambiguity. Second, we need to see “Dupixent-like” or better efficacy numbers—that 25% to 33% skin clearance rate needs to be at the higher end of that range, or even exceed it, to get people truly excited. Finally, the safety profile must be pristine. The best-case scenario would be no new serious adverse events, which would help contextualize the Kaposi’s sarcoma case as a tragic but likely isolated incident. If Sanofi can deliver two clean, highly effective, and safe trials, it would not only secure amlitelimab’s future but also breathe new life into the entire OX40L mechanism as a legitimate therapeutic pathway.
What is your forecast for the next generation of eczema treatments?
My forecast is a move toward greater personalization and convenience. We’re seeing a shift from “one-size-fits-all” blockbusters to a more stratified approach. The next wave will likely include more oral medications, moving away from injectables for patients with moderate disease, and potentially even more targeted biologics with even longer dosing intervals than amlitelimab’s proposed 12 weeks. I also anticipate a deeper focus on long-term safety and durability of response. The market is maturing; it’s no longer enough to just show a drug works. The winning treatments of the 2030s will be those that offer sustained relief with the least possible disruption to a patient’s life and an absolutely pristine long-term safety profile. The bar is getting higher, and companies that can deliver on that complete package will lead the next era of eczema care.
