Tuesday, July 14, 2015

Anacor reports positive Phase 3 data on PDE4 inhibitor ANA2728 (Crisaborole)

In yesterday's issue of UpdatesPlus-Atopic Dermatitis** we reported that Anacor has fully enrolled two Phase 3 pivotal ANA2728 studies and that data were expected this quarter.  Data were released yesterday [Link]

**UpdatesPlus is our regular report analyzing breaking development across the field of atopic dermatitis research and development - for further information and sample copies  please contact Dr Jon Goldhill
  • ANA2728 now known as Crisaborole is a topical PDE4 inhibitor.  The molecule is based on Anacor's boron based chemistry which is intended to increase skin penetration
  • Each of the two studies enrolled 750 patients aged 2yo and treated for 1 month
  • Patients had mild-moderate dermatitis covering approximately 18% of the skin.  Approximately 60% patients had moderate disease
  • The primary endpoint (ISGA 0/1 - clear/nearly clear, with a minimum of a 2 grade improvement) was improved in both studies from 25%-18% with vehicle to 33%-31%.  This produced a delta of 7% and 13% in the two studies
  • During Anacor's investor call, the company highlighted the secondary endpoint, ISGA 0/1 (without a requirement for a 2 grade improvement) as clinically more important.  This was improved from 41-30% to 52%-59% (delta of 11% and 19%)
  • Efficacy was achieved within 8d (see below).  The safety profile was benign and the only measure worthy of mention is a small increase in application site pain (1.2% vs 4.4%).  Severity of pain was not reported however there was no increase in discontinuation between test and vehicle
  • A long term safety study is now underway.  During the results call it was disclosed that 500 patients had enrolled

Comments:  During Anacor's call, market research was presented claiming that there is a large unmet need in the atopic dermatitis market with high potency corticosteroids producing excessive adverse events.  The benign safety profile of Crisaborole suggests benefit in this respect although a active control arm allowing comparison of efficacy between the two strategies would have been useful.  On the other hand, low potency corticosteroids are viewed as being insufficient in resolving itch.  The present study suggests that rash is resolved in up to 60% patients.  Again an active comparator arm would have been useful.

Of note one non-steroidal comparator, Elidel (pimecrolimus) produces clear/nearly clear rates of 35% at 6wks.  This is nominally lower than for Crisaborole although the Elidel vehicle response was also markedly lower (18%).  It is unclear at present therefore how much of the power of Crisaborole lies in its vehicle.  Indeed Crisaborole vehicle produced clear/nearly clear rates very similar to Elidel response (30-41% vs 35%).   Quite how important or relevant this is is unclear.  Anacor actively set out to rationally optimize its vehicle.  Moreover the important issue is the degree of efficacy seen with the product in its entirety.  The observation does however suggest the possibility of developing the vehicle alone as a maintenance treatment for some patients.

Data were not reported on itch and this is eagerly awaited.  Of note, in our UpdatesPlus report yesterday we suggests that evidence, particularly from topical tofacitinib studies, suggests a dissociation of rash and itch resolution.  Given the importance of itch as a patient reported out come it will be important to note how Crisaborole improves itch.  The company was asked about this in its call and commented that data were not yet full analyzed but appeared promising, including in terms of speed to response

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