Friday, May 22, 2015

Amgen pulls out of brodalumab development amongst fears of suicidality - bad luck, bad target or victim of brodalumab's efficacy

This content is sampled from our UpdatesPlus service. UpdatesPlus-Psoriasis is a regular monitoring and analysis service from our inflammation and dermatology collection. Reports are accompanied by ad hoc e-mail alerts providing near real time analysis of key breaking events.  This alert along will all other recent events will be analyzed in our next issue of UpdatesPlus.  Please contact - or access our UpdatesPlus product brochure for further details 

Update [31st July 2015]:  AstraZeneca seems likely to continue brodalumab development with new partner [more]

  • Amgen and AstraZeneca has been collaborating since 2012 on the development of 4 mAbs from Amgen's inflammation portfolio including IL-17R mAb, brodalumab
  • Amgen has however now announced that it will be terminating development of brodalumab
  • Brodalumab was in development for psoriasis, psoriatic arthritis, and axial spondyloarthritis
  • The decision was based on suicidal ideation and behavior.  Amgen believes this would have restricted labeling
  • The company has commented that "During our preparation process for regulatory submissions, we came to believe that labeling requirements likely would limit the appropriate patient population for brodalumab"
  • Amgen is now starting to transition the brodalumab program to AstraZeneca who now has the right to file (outside of Asia where Kyowa Hakko Kirin has rights)
Comments:  Despite high efficacy in Phase 3 studies, whispers of suicidality associated with brodalumab started to emerge at AAD.  At the time Amgen suggested this was related to disease however the company refused to comment on total rates and whether events were seen across arms.  At the time we commented that Amgen's suggestion that suicidality related to disease rather than drug was curious.   If this had have been the case events would have been expected to be skewed towards placebo groups where patients would have been less likely to achieve skin clearance.  In turn Amgen would have been expected to clarify this to protect brodalumab.  This was not the case.  Since suicide ideation is increased in patients with psoriasis, we agree with Amgen that a labelled warning of this adverse event could have been detrimental (although we note that this is a labelled warning for Otezla which has had a good launch).  The question is whether Amgen is being hyper-cautious or whether the risk of suicidality is especially concerning.  Questions also emerge around the cause of risk - is this a spurious cluster of events unrelated to brodalumab; is suicidality perhaps related to relapse from the excellent efficacy associated with brodalumab after withdrawal (remember most patients exhibited at least PASI 90 on treatment but durability was very poor upon withdrawal); or perhaps suicidality is related to blocking the IL-17RA (note that suicidality has not to our knowledge been reported for the IL-17A ligand mAb Cosentyx).  Questions also relate to whether AstraZeneca will file brodalumab.  Against the exceptional performance of Consentyx and also ixekizumab, as well as the apparently inferior durability of broadulamab vs  IL-17 ligand mAbs and now the possibility of suicide ideation warnings, the fate of brodalumab remains to be seen.  One final point is whether regulators will now reevaluate suicide risk of IL-17 related molecules as a class - much greater clarity of brodalumab data is required to make a judgement

Labels: , , ,


Post a Comment

<< Home