AstraZeneca further ups its biologics manufacturing capacity - further evidence of future brodalumab production?

In our recent alert announcing Valeant's decision to in-license psoriasis candidate, brodalumab from AstraZeneca we commented that the deal may suffer from a lack of manufacturing capacity for biologics.  AstraZeneca appears to be making a concerted effort to expand manufacturing capacity potentially addressing this

• AstraZeneca has recently invested $285M in its Swedish biologics facility.  Capacity at an existing Maryland site is also to be expanded (see our original alert below)
  
• Now AstraZeneca has announced  the purchase of a biologics bulk manufacturing facility from Amgen in Colorado
• AstraZeneca reportedly plans to start staffing the facility immediately to support refurbishment and infrastructure improvements
• Once complete, the site is expected to be operational and licensed for commercial production by late 2017
• The facility will eventually double AstraZeneca's biologics manufacturing capacity in the US.

Comments:  Across the AstraZeneca/Medimmune pipeline at least 6 mAbs may be in a position to launch in the near term (Durvalumab, Moxetumomab and Tremelimumab for oncology and brodalumab, Benralizumab and Tralokinumab for immunology).  New capacity will be required to meet this over demand.  Although it is unclear whether AstraZeneca will be responsible for brodalumab manufacture under its deal with Valeant,  today's new makes it increasingly likely that it will be able to do so if necessary.  Furthermore until Amgen's recent decision to drop brodalumab it may have even been the intent to manufacture commercial supply at the Colorado site suggesting that processes are up and ready to rapidly meet demand

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Valeant in-licenses global rights to brodalumab outside of Japan and other Asian geographies as it further grows into the dermatology space

Valeant in-licenses global rights to brodalumab

From: UpdatesPlus-Psoriasis our regular psoriasis monitoring and analysis service

• Just a few weeks ago we reported that AstraZeneca seemed likely to continue brodalumab development and that a new partner was being sought to replace Amgen
• Amgen had earlier decided to discontinue development due to concerns over labelling relating to suicidality (See Amgen pulls out of brodalumab development amongst fears of suicidality - bad luck, bad target or victim of brodalumab's efficacy)
• Valeant has now announced that it will in-license global rights to brodalumab from AstraZenecca.  
• Valeant will make an upfront payment of $100M to AstraZeneca, with another $170M in prelaunch milestones and up to $175M following launch
• Valeant will license exclusive global development and commercialization rights to brodalumab with the exception of Japan and certain other Asian countries where rights are held by Kyowa Hakko Kirin under a prior arrangement with Amgen
  
• After approval, AstraZeneca and Valeant will share profits although the profit split has not to our knowledge been disclosed
  
• EU and US filing is expected Q4 2015
• Valeant will assume all development costs associated with the regulatory approval for brodalumab

Comments:  Valeant had extensive commercial experience across the dermatology spectrum including actinic keratosis, acne and atopic dermatitis. A Steroid/Retinoid combination is expected to be filed for psoriasis in 2016.  Acquiring brodalumab could significantly expand Valeant's position in dermatology.  Under the terms of the current deal it seems that AstraZeneca will not be commercializing brodalumab if approved and instead Valeant will be responsible for this.  With Valeant's existing activity in dermatology and a limited level of AstraZeneca sales activity, this agreement seems logical.  On the other hand the deal will allow AstraZeneca to focus on immuno-oncology.  One barrier Valeant could face is its limited experience in biologics and in this respect it is of interest that AstraZeneca recently announced plans to invest $285M in a new biologics manufacturing facility in Sweden. The new plant will be focused on filling and packaging of protein therapeutics. Clinical trial material will be generated by 2018 with commercial capacity coming on line by 2019.  Biologics capacity at an existing site in Maryland is also reported to be expanded.  It is not known if these sites are to be responsible for brodalumab manufacture/filling - if this is however the case, brodalumab capacity may suffer a lag during the initial role out period (ie 2017/18)

Read more in our next issue of UpdatesPlus-Psoriasis our regular monitoring and analysis service. Reports are accompanied by ad hoc e-mail alerts providing near real time analysis of key breaking events. This alert along with all other recent events will be analyzed in our next issue of UpdatesPlus. Please contact jon.goldhill@leaddiscovery.co.uk

AstraZeneca suggests that it will be proceeding with brodalumab development

• AstraZeneca held its Q2 results call yesterday and hinted at continued development of brodalumab
• The future of brodalumab had been put in doubt earlier this year with Amgen announcing that it was no longer going to develop brodalumab in the US [see our earlier post]
  
• Amgen consequently transitioned rights to AstraZeneca
• Amgen stated its decision was due to reported suicidality and ideation of suicide in brodalumab trials
• While Amgen has yet to disclose the level of risk, it commented that there was a fear of labelled monitoring requirements diminishing the competitiveness of brodalumab
• During the company's comments AstraZeneca commented that an initial evaluation of data suggested that suicidality was likely unrelated to brodalumab
• It was also commented that it had received multiple partnering offers but that it was completing data analysis prior to selecting a partner
• On the slide deck accompanying the results call, brodalumab filing continues to be listed as 2015

Comments: The full reasons behind Amgen's decision to abandon brodalumab continue to be elusive.  The fact that AstraZeneca is muting possible licensing suggests others are less concerned that FDA requirements will reduce the competitiveness of brodalumab however a 2015 filing would seem unlikely in the US unless AstraZeneca opts for a commercial license handling  submission itself


Call quotes:  As for brodalumab we have conducted an initial evaluation of the data, which confirms that broda demonstrated strong efficacy in psoriasis and indicates that the observations of suicide or ideation are unlikely to be causally related to brodalumab therapy....we've actually had several expression of [partnering] interest. In fact we've already received offers, and we are considering those and engaging in discussions with potential partners. But it was really encouraging to see that we didn't get one, we got several expressions of interest from a variety of partners...But the key is really first of all to go through the data in more details, and that's what we are still doing. And secondly decide how we progress this together with the partner that we would select.

Read more in our next issue of UpdatesPlus-Psoriasis our regular monitoring and analysis service. Reports are accompanied by ad hoc e-mail alerts providing near real time analysis of key breaking events. This alert along with all other recent events will be analyzed in our next issue of UpdatesPlus. Please contact jon.goldhill@leaddiscovery.co.uk

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 jon.goldhill@leaddiscovery.co.uk - 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