BMS returns the rights on rheumatoid arthritis candidate, clazakizumab to Alder

The following alert is part of our UpdatesPlus - Rheumatoid Arthritis service.  Read more about clazakizumab and other advances in the field in our August issue  available from fiona.watts@leaddiscovery.co.uk

• BMS has returned the rights to IL-6 mAb, clazakizumab to Alder[link]

• This reportedly follows pipeline reprioritization at BMS rather than efficacy or safety concerns

• 12wk clazakizumab data from a Phase 2b study of MTX-IR rheumatoid arthritis patients was reported at ACR 2013; 24wk data have since been reported at EULAR 2014 and a new TNF-IR study has opened. The second study remains on track to read out in 2015

• Efficacy was high at 24wks in the MTX-IR study (83% ACR20; 48% ACR50), and apparently similar with or without MTX. Serious infections continue to present the greatest AEs especially at higher doses (5%)

• Phase 2b PsA data will be presented at ACR later this year

Comments:  We find BMS' decision a little surprising given the good efficacy reported to date for clazakizumab. During its conference call earlier today, Alder stressed that no new data have emerged that drove BMS' decision. One potential issue that may slow down development and which may have contributed to BMS' decision is the apparent inability to so far select an optimal dose.  Dose ranging studies to date have reported similar efficacy across  doses (25-200mg, q4w).  Of note, Alder has now confirmed that the TNF-IR study is looking at doses under 25mg (the lowest dose investigated in the MTX-IR study).

Another issue is that the IL-6 space is currently competitive, with (Ro)Actemra sales evolving impressively (20-30% YoY growth) and Sarilumab under late stage development.  Clazakizumab is different from both of these molecules in that it targets IL-6 rather than its receptor.  This offers novelty however J&J/GSK have taken a similar approach with sirukumab which is more advanced and currently in Phase 3.  This level of competition may be acceptable to a smaller company such as Alder willing to take a relatively small share of a large IL-6 market, but less so for BMS.  BMS appears to have shaken up its rheumatoid arthritis portfolio recently. BMS-817399, a CCR1 antagonist appears to have been terminated, at least for rheumatoid arthritis following reports of poor efficacy.  BMS-986104 has however entered the pipeline.  The MOA of this candidate is unknown but is orally active