Eular 2022 – a new IL-17 threatens to underwhelm

At first glance, Friday’s mid-stage data on izokibep, the anti-IL-17 agent under development by Affibody, Acelyrin and Inmagene Biopharmaceuticals, look pretty competitive on a cross-trial basis. Look closer, however, and there are reasons to doubt that the product can take on the therapies that are forecast to become the leaders in this indication. Acelryn states that izokibep’s “high potency and small molecular size” allow it to reach similar exposure levels through a subcutaneous injection that antibodies require IV administration to achieve. But Cosentyx and Taltz, forecast to be the biggest selling anti-IL-17 MAbs in psoriatic arthritis in 2028 according to Evaluate Pharma, are both delivered subcutaneously – and less frequently than izokibep. And the drug forecast to be the top seller for psoriatic arthritis in 2028, Abbvie’s Rinvoq, is a pill. At least oral IL-17s might not be an immediate threat; several of these are in early or mid-stage trials, but not in this disease. If izokibep is able to maintain this level of efficacy in phase 3, ideally while being dosed half as often, it will still have grave difficulty making a splash in this highly competitive space. 

Battle of the anti-IL-17s
Company Affibody, Acelyrin, and Inmagene  Novartis Lilly
Project Izokibep 80mg Q2W Izokibep 40mg Q2W Placebo Cosentyx 150mg Q4W Cosentyx 300mg Q4W Placebo Taltz 80mg Q4W Placebo
Trial ABY-035-202 (Ph2; NCT04713072) Future 5 (Ph3; NCT02404350) Spirit-P1 (Ph3; NCT01695239)
N 135 100 100 98 107 106
ACR50 at wk16 (%)* 52 48 13 37 35 6 34 5
Forecast 2028 sales ($m) - 823 1,089
*At 12wk for Taltz. Patients in the Cosentyx and Taltz trials were TNF-alpha-naïve. Source: company communications, drug labels.

*Wk12 for Taltz. ACR50 is a composite measure defined as both a 50% improvement in the number of tender and number of swollen joints, and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure (most often Health Assessment Questionnaire), visual analogue pain scale, and erythrocyte sedimentation rate or C-reactive protein. Source: company communications; drug labels.

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