Week's news analysis

is it the right time for Biogen?

By The Editor - 16 July 2020

Amid the Covid-19 pandemic and the desperate search for either a treatment or a vaccine, companies are doing "business as usual" on others therapeutics fields. This is the case of Biogen and partner Eisaï for the treatment of Alzheimer's disease.

Beginning of July, the companies have submitted a "biologics license application" (BLA) to the FDA for their potential but controversial aducanumab product. The agency has 60 days to decide whether to accept it or issue a complete response letter. If approved by the FDA, the application will be reviewed. Biogen bets the drug will be granted "priority status" due to the disease's unmet medical need, with the review being completed within 6 months instead of the 10 months it normally takes.

No drug has been approved in the past 17 years to treat Alzheimer's disease although the global social burden of the disease is expected to grow as the population ages. Almost 99 % of the 190 research programs on drugs developed have failed clinical trials in the last ten years. There are currently only four approved drugs which treat the symptoms of the disease affecting nearly 19 millions of people in the OECD (and 5 millions Americans among them). A figure that is likely to double by 2030...

The american biotech needs to convince the FDA, amid concerns over patents for its multiple sclerosis drug Tecfidera against Mylan and competition for its spinal muscular atrophy treatment Spinraza, under intensified competition with pending US approval of Roche's Risdiplam.

But analysts remain skeptical on the "clinical data package" of aducanumab. J.P. Morgan estimates the possibility of success of the whole regulatory process at 55 %, while others consider the therapy to have only a 33 % probability of success.

Indeed, aducanumab is a controversial subject among professionals. As J.P Morgan analysts suggest, "the majority of doctors don't believe that aducanumab should be approved... but plan to prescribe the drug to a substantial number of early Alzheimer's patients if it reaches the market".

The treatment under review is based on the approach on BACE inhibitors, aimed to prevent a protein from producing the amyloid that builds up in the brains of Alzheimer's patients and form deposits, called plaques. Biogen's product works to clear amyloid plaques in the brain. The history of this drug candidate has been highly eventful, so far.

Biogen's two trials Engage and Emerge have been criticized and were discontinued in May 2019. They reversed course in October and revived plans to seek US approval, claiming that positive results from a new analysis of the trials backed the effectiveness of high-dose aducanumab when administered to patients over an extended period.

In March 2020, Biogen started a new Phase IIIb open-label, multicenter safety study of aducanumab named Embark, which was halted due to the Covid-19 pandemic. The completed submission of July 2020 includes clinical data from the Phase 3 Emerge and Engage, as well as the Phase 1b Prime study. If approved, aducanumab could become "the first therapy to reduce the clinical decline of Alzheimer's disease and would also be the first therapy to demonstrate that removing amyloid beta resulted in better clinical outcomes", outlined the companies.

Will an Alzheimer's drug, that slows the progress of the brain disorder instead of treating the symptoms, ever come to market? Several announcements of failed Alzheimer's treatments over the past months disappointed both markets and investors.

The latest setback was in February 2020 when Roche and Eli Lilly announced that results from the Phase II/III DIAN-TU-001 study showed that the experimental anti-amyloid drugs gantenerumab and solanezumab did not significantly slow the rate of cognitive decline in patients who have an early-onset, inherited form of Alzheimer's disease, compared with placebo.

Previously, in January 2019, Roche and partner AC Immune stopped two Phase 3 studies (known as Cread 1 and Cread 2) of their drug Crenezumab in Alzheimer's early, after an interim analysis by a committee of investigators showed those trials were likely to fail. The drug had already shown disappointing Phase 2 results in 2014.

In June 2018, AstraZeneca and Eli Lilly announced they scrapped two late-stage trials of their experimental Alzheimer's drug, Lanabecestat, they have co-developed since 2014. In 2016, solanezumab from Eli Lilly, already failed a study called Expedition 3 in patients with early Alzheimer's, after two failed trials in 2012 (Expedition 1 and Expedition 2) in later-stage patients.

Others companies also stopped their trials, like Pfizer in January 2018, Axovant Sciences Ltd or Merck and Co, with verubecestat, that failed in 2017 on a clinical trial of patients with mild to moderate Alzheimer's. Boehringer Ingelheim also decided to axe its BACE inhibitor drug, too, following another trial failure.

A new R& D approach is targeting the protein tau, another degenerative process identified in the brain of Alzheimer's patients. Tau protein forms into tangles, which start in the areas of the brain important for memory. Several companies are working on this approach. Roche and AC Immune are among them with an anti-tau drug, RG 1600, which is in Phase 2 testing. In December 2018, Eli Lilly signed an agreement with AC Immune worth up more than $1.7 billion to target the tau tangles too. But it is not completely clear if tau, like amyloid, is causing the disease.

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