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

For detailed analysis of immunology pipelines, R&D activity and commercial activity ask us about UpdatesPlus - sample 100 page reports available on request

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

Vandetanib is approved in the US for medullary thyroid cancer

About 44,600 new cases of thyroid cancer were diagnosed in the US last year, with about 1,690 of those resulting in death, according to the US National Cancer Institute. Medullary thyroid cancer is estimated to represent up to 5% of all thyroid cancers, with about 2,200 patients being diagnosed last year with that form of the disease.

Multi-targeted tyrosine kinase inhibitors dominate the thyroid cancer pipeline (see: Pipeline Insight: Cancer Overview Malignant Melanoma, Neuroendocrine Tumors and Thyroid Cancer). There are four late-stage drugs which are forecast to achieve sales of $97m by 2019. It has long been thought likely that at least one of the late-stage drugs will be the first agent approved specifically for medullary thyroid cancer.

Likelihood has now become reality as the FDA has approved orphan drug vandetanib for the treatment of thyroid cancer.

The safety and effectiveness of AstraZeneca's vandetanib were established in a single, 331-patient randomized international Phase III ZETA study designed to measure progression free survival in patients with late-stage medullary thyroid cancer.

The results showed a median PFS of 16.4 months in the placebo arm and at least 22.6 months in the vandetanib arm. Final progression-free survival in patients treated with vandetanib has yet to be disclosed; moreover, overall survival data re not currently available.

Despite these two issues, vandetanibdoes represent an advance in the treatment of thyroid cancer, but not without a price. Vandetanib's labeling comes with a black-box warning of QT prolongation, torsades de pointes and sudden death. Because of those risks, AstraZeneca was required to implement a risk evaluation and mitigation strategy (REMS) plan for vandetanib,.

While the majority of medullary thyroid cancer cases are sporadic, approximately 20% to 25% are hereditary, caused by inherited mutations in the RET proto-oncogene, which drives the growth of malignant cells. Approximately 25-60% of sporadic MTCs have a somatic mutation of the gene as well.

Vandetanib inhibits RET, as well EGFR and VEGFR, which are involved in cell proliferation and angiogenesis in a number of different tumour types.

Vandetanib is also in Phase II development for the common forms of thyroid cancer (follicular and papillary).