AstraZeneca Unburdens Itself Of Brodalumab
This article was originally published in Scrip
AstraZeneca plc has managed to offload the dermatology candidate brodalumab to Valeant Pharmaceuticals International Inc following Amgen's decision to pull out of a co-development deal earlier this year. Amgen made the move owing to potential side effect issues, with suicidal thoughts being linked to brodalumab administration during clinical development, despite evidence of efficacy.
AstraZeneca has now granted Valeant an exclusive license to develop and commercialize brodalumab, an IL-17 receptor monoclonal antibody in development for patients with moderate-to-severe plaque psoriasis and psoriatic arthritis.
Under the agreement, Valeant will hold the exclusive rights to brodalumab globally, except in Japan and certain other Asian countries where rights are held by Kyowa Hakko Kirin Co Ltd under a prior arrangement with Amgen, the originator of brodalumab. Valeant will assume all development costs associated with the regulatory approval for brodalumab. Regulatory submission in US and EU for brodalumab in moderate-to-severe psoriasis is planned for the fourth quarter of 2015, according to the companies.
Valeant will make an up-front payment to AstraZeneca of $100m as well as additional pre-launch milestones of up to $170m and further sales related milestone payments of up to $175m following launch. After approval, AstraZeneca and Valeant will share profits.
The transaction is expected to complete in the fourth quarter of 2015, subject to customary closing conditions, and it does not materially impact AstraZeneca's financial guidance for 2015. The upfront payment and any potential subsequent milestone payments are expected to be reported as externalization revenue.
Amgen and AstraZeneca formed a collaboration in April 2012 to jointly develop and commercialize six monoclonal antibodies from Amgen's clinical inflammation portfolio, including brodalumab. Amgen decided to discontinue development of brodalumab in May 2015. The collaboration arrangements remain in place for the other programs.
Brodalumab is supported by data from the three AMAGINE Phase III pivotal studies, which demonstrated that brodalumab has an effective mechanism of action. At the 210 mg dose, brodalumab was shown to be efficacious in total skin clearance of psoriasis compared to placebo and superior to ustekinumab (Johnson & Johnson's anti-IL-12/23 Stelara) at week 12 in two replicate comparator trials involving over 3,500 patients.
J. Michael Pearson, chairman and CEO of Valeant, described brodalumab as "potentially the most efficacious therapy yet for moderate-to-severe plaque psoriasis."
However, experts have said that recent therapeutic successes with novel therapies for psoriasis, notably anti-IL17a therapies such as Lilly's ixekizumab, which has been filed for approval, and Novartis's successfully launched Cosentyx (secukinumab), mean that the efficacy bar for new treatments should be raised.
Deutsche Bank analysts would agree. The current mainstay of treatment for more severe psoriasis patients, after cheaper topical/oral agents, is the well-established anti-TNF biological drug class followed by J&J's Stelara, they note. However Cosentyx, which was launched in early 2015, has "hit the ground running," generating $30m in its first full quarter of sales. "We forecast $4.5bn of 2023 sales for the IL-17 class with Cosentyx generating $3.6bn, supported by its first mover advantage."
The potential mechanism of the suicidal ideation observation is unclear. Brodalumab is broader acting than the other IL-17A antibodies – Cosentyx and Lilly's ixekizumab – as the latter two bind specifically to the IL-17A ligand whereas brodalumab targets the IL-17A receptor, with the resulting blockade of more IL-17A cytokine subtypes.
Damningly, Deutsche analysts expect "brodalumab to either not launch or generate minor sales." They say that physician feedback suggests brodalumab now has "no future, even if there turns out to be no link, given the importance of safety with these drugs and the number of alternatives available."