Roche Bets up to $830M On Evotec's MAO-B for AD
BioWorld Today Correspondent
LONDON – Evotec AG has out-licensed its lead monoamine oxidase type B (MAO-B) product for Alzheimer's disease in a $830 million deal with Roche AG, taking $10 million up front, followed by short-term clinical milestones of $170 million and the balance to come in commercial milestones.
In addition, Roche is assuming all development and commercialization costs. The Basel, Switzerland-based pharma will start a large Phase IIb trial in 2012 powered to demonstrate that the orally available product, EVT 302, slows the progression of symptoms of Alzheimer's, and paving the way for a pivotal Phase III study.
The compound was originally licensed from Roche to Evotec in 2006, and was initially developed as a smoking cessation treatment. In May 2009 it failed to demonstrate efficacy in a Phase II proof-of-concept trial involving 414 smokers in which EVT 302 was tested alone and in combination with a nicotine replacement patch.
An earlier MAO-B inhibitor, EVT 301, also licensed from Roche, failed in a Phase I program in the treatment of Alzheimer's disease in 2006.
Werner Lanthaler, CEO of Evotec, said he is "very happy" Roche has decided to take back EVT 302, in what he claimed will be "the largest effort" in Alzheimer's disease drug development, with the clinical program costing "more than €100 million" (US$140.07 million).
While he was not prepared to give a specific timetable, Lanthaler said the clinical development program will be very fast, with Roche currently preparing for the Phase IIb.
"There will be full commitment and full speed. It will be much faster than many people think," he said during a conference call held to discuss the deal.
To date, no drug has demonstrated the ability to slow the progress of Alzheimer's disease, with all Phase III trials that have reported to date failing, Lanthaler noted. Meanwhile, drugs targeting the beta-amyloid pathway are yet to achieve proof of concept.
"The Evotec/Roche MAO-B program represents an alternative and potentially complementary approach [to beta-amyloid targeted drugs]," Lanthaler said.
Lanthaler claimed Hamburg, Germany-based Evotec has overcome the interaction with dietary tyramine seen with previous MAO-B inhibitors, saying EVT 302 has "a perfect safety profile."
He added, "We think it is the perfect molecule to test in Alzheimer's disease; Evotec has produced a robust clinical and preclinical development package."
MAO-B is responsible for the breakdown of certain neurotransmitters in the brain, and its activity is linked to the production of reactive oxygen species, causing oxidative stress and neuronal damage. The enzyme has been shown to be overexpressed in the postmortem brains of Alzheimer's sufferers, and it is proposed that blocking its activity will slow progression of the disease.
Evotec's Phase I data include PET studies that show it is possible to completely inhibit production of MAO-B with orally administered EVT 302. There were no safety or tolerability concerns with dosing of up to eight weeks.
In September 2006 Evotec discontinued development of the earlier compound EVT 301, following indications of potential liver toxicity in a Phase I trial in healthy volunteers. Roche had earlier put EVT 301 through five Phase I trials, but all of those were of a shorter duration, and did not highlight the liver toxicity.
EVT 301 was related to a predecessor MAO-B inhibitor, which had failed a Phase III trial in Alzheimer's, the results of which were not published. EVT 302 has a different chemistry from the earlier compounds.
Evotec has kept faith with the potential of MAO-B inhibition in Alzheimer's disease, pushing on with the development at a time when most of the other drugs in late-stage development for Alzheimer's, such as Eli Lilly and Co.'s solanezumab, Genetech's crenezumab and Roche's gantenerumab, target the beta-amyloid pathway.
Lanthaler said targeting MAO-B represents both a true alternative and a potential additive approach to beta-amyloid.
Published: September 7, 2011
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