Wednesday, September 24, 2014

Celgene has announced FDA approval of Otezla (apremilast) for the treatment of psoriasis -

This alert is from our UpdatesPlus-Psoriasis and UpdatesPlus-Spondyloarthopathies.  To get more alerts like this and our full monthly reports highlighting and analyzing all key advances in the area please contact fiona.watts@leaddiscovery.co.uk
  • Otezla (apremilast) was first approved for the treatment of psoriatic arthritis in March 2014
  • The label modification is "Patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy"
  • Approval was based on ESTEEM 1 and ESTEEM 2 demonstrating efficacy in treatment-na├»ve and -experienced patients including those previously treated with biologic agents or conventional systemic agents
  • The revised label reports publicly (we believe for the first time) rates of depression
  • During the 16wk blinded period of the ESTEEM studies 1.3% (12/920) of subjects treated with Otezla reported depression compared to 0.4% (2/506) treated with placebo.

Comments:  Otezla produced PASI-75 rates of 29-33% over 16wks in the ESTEEM program with an excellent safety profile.  Safety and freedom from monitoring would be expected to drive uptake early in the psoriasis treatment paradigm despite the relatively low efficacy in the context of new biologics.  Of note however, although efficacy is modest, PASI improvement is highly durable over 52wks (data presented at ADD), suggesting those patients who respond well to Otezla can expect to remain on treatment for an extended period.  As mentioned above, the revised label describes rates of depression.  Depression has already been flagged as a potential AE of Otezla at the time of approval for psoriatic arthritis.  In the PALACE studies however, the rates of depression appear similar between control and Otezla treated patients (1% vs 0.8%), and we interpreted the label warning of depression as being class related (roflumilast, another PDE4i is associated with increased depression).  According to the revised label, the increase in depression rates was larger in psoriasis studies (1.3% vs 0.4%).  It is unclear if this is significant.  More importantly, the rates of severe depression; discontinuation due to depression or; of suicidality were very low across treatment groups.  Against this it should be considered that depression is a co-morbidity of psoriasis and it will be interesting to see in real world studies whether depression is worsened in patients with pre-existent depression when receiving Otezla.  One final word; the new indication should help drive Otezla uptake significantly.  In our most recent issue of UpdatesPlus-Spondyloathropathies, we comment on excellent early uptake for psoriatic arthritis with Celgene claiming that Otezla was tying with Humira for the leading new to treatment choice after DMARDs. This represents a 20% share of this cohort.  Celgene has not yet been able to message skin data as the FDA requires specific psoriasis studies for this.  With the new approval however, Celgene reps will not only be able to more easily approach dermatologists, they will also be able to message skin data to rheumatologists further driving uptake in patients with psoriatic arthritis.

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