Strike Novartis from the list of rivals to Incyte’s topical eczema drug Opzelura. After getting a look at early clinical data, Novartis has dumped (PDF) its topical pan-JAK inhibitor CEE321 over an unfavorable risk-benefit profile.
Novartis talked up the molecule at its R&D day late in 2019, pitching it as a potential first-in-class topical “soft” pan-JAK inhibitor. The idea was to achieve strong therapeutic effects in the skin without causing the systemic effects associated with oral administration, and thereby deliver a drug suitable for use in the treatment of children with mild to moderate atopic dermatitis.
At that time, Novartis had shown CEE321 inhibited biomarkers of atopic dermatitis in simulated human skin and found drug concentration in minipig skin was more than 25,000-fold higher than in blood after topical administration. Buoyed by the data, Novartis moved into a phase 1 clinical trial.
Novartis started testing CEE321 in healthy subjects in February 2020, before modifying the protocol to include atopic dermatitis patients several months later. The 28-participant phase 1 trial wrapped up in May 2021.
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The story sours after that. Having reviewed its data, Novartis has determined CEE321 has an unfavorable benefit-risk profile, prompting it to discontinue the program rather than advance deeper into the clinic. Novartis disclosed the discontinuation in a quarterly update to its drug development pipeline.
Novartis envisaged CEE321 as a new option for patients with mild to moderate atopic dermatitis whose symptoms are unresolved after receiving existing topical therapies. At that time, Sanofi and Regeneron’s Dupixent was available for moderate to severe patients and oral JAK inhibitors targeting the same set of patients were coming down the pipeline, but Novartis saw a gap at the milder end of the spectrum.
Other companies saw the same opportunity. Last year, Incyte became the first company to win approval for a topical JAK inhibitor in the U.S., but its label carries safety warnings. Leo Pharma has a prospect in phase 3, and a clutch of companies are in midphase development. Novartis once thought it could muscle through the pack and become a leader in the space. The phase 1 data ended that plan.