Eisai and Biogen have opted to take their BACE inhibitor E2609 into phase III trials, raising hopes of a new treatment option for Alzheimer’s disease.
The US FDA has indicated there is sufficient evidence of efficacy for the orally-active drug to warrant late-stage testing, according to Eisai. The agency also said after the end-of-phase II meeting on 20 July that it was happy with two clinical trial designs put forward for the phase III programme.
Eisai and Biogen want to carry out an international study of E2609, so discussions still need to take place with regulatory authorities in the EU and Japan. The protocol will recruit patients with early Alzheimer’s disease who will be randomised to treatment with either E2609 or placebo over a period of two years.
The outcome of the FDA discussions is a further boost for companies developing BACE inhibitors, which along with Eisai/Biogen also include Merck & Co, AstraZeneca/Eli Lilly and Amgen/Novartis, among others.
Merck has already started phase III trials of its MK-8931 candidate, while Lilly and AZ recently did likewise with AZD3293. Novartis and Amgen’s CNP520 is in phase I/II testing.
BACE (beta secretase cleaving enzyme) is one of the enzymes involved in the creation of amyloid plaques in the brain – a hallmark of Alzheimer’s disease – and it is hoped that inhibiting it might slow the progression of the disease.
If effective, this would represent the first time that any drug has been able to interfere with the underlying neurodegeneration in Alzheimer’s disease. At the moment, all available treatments are aimed at boosting the activity of nerve cells in the brain but do not stop them dying off.
The list of amyloid-targeting drugs that have been withdrawn from development is long, however, and the BACE inhibitor class has run into its own share of problems. Roche, Boehringer Ingelheim/Vitae Pharma and Lilly have all scrapped or halted BACE inhibitors in the last few years.
One issue seems to have been difficulties in achieving a high level of selectivity for BACE-targeting compounds, so that they inhibit amyloid without affecting other systems such as the myelin sheaths that surround nerve cells.
In a phase II trial E2609 was able to reduce levels of beta amyloid in the plasma and cerebrospinal fluid (CSF) and was well tolerated, with a single 50mg/day dose selected for phase III trials.
It is notable that the other phase III trials involving BACE inhibitors have looked at more than one dose in order to look at dose response and weigh up safety and efficacy.
Eisai said recently it is confident in its one-dose approach and believes this design will result in a smaller, faster study that could allow it to catch the leaders in the BACE race.