Nearly two months after landing the controversial FDA nod for its Alzheimer's drug Aduhelm, Biogen has some early-stage but positive news to share on its tau-targeting treatment for the neurodegenerative disease.
Biogen's 2019 $45 million upfront bet on Ionis Pharmaceuticals' antisense treatment is paying off. The two companies said Tuesday that a phase 1b study of the treatment, BIIB080/IONIS-MAPTRx, was safe and tolerable in patients with mild Alzheimer's disease (AD).
This comes around six weeks after Biogen threw out a late-stage asset in gosuranemab, a drug also targeting tau in AD, and part of a $300 mill Bristol Myers pact. The trial missed its primary efficacy endpoint, failing to halt the rate of clinical progression in patients, and the pair decided to call it a day. It will hope to have better luck with BIIB080/IONIS-MAPTRx, though Bernstein analysts wrote the chances of success at this stage with its second hopeful were low.
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While Aduhelm (aducanumab) targets amyloid plaques, the Alzheimer's research community's most invested area, BIIB080 is focused on lowering tau protein, another big focus in recent years. The companies presented the results at the 2021 Alzheimer's Association International Conference in Denver.
All patients in the small study were white, according to a Bernstein analyst's note. Biogen and Ionis spokespersons didn't immediately respond to requests for comment on trial demographics. Trial diversity, across the healthcare spectrum, has come to the forefront in the past year amid the pandemic, and Aduhelm's approval has come with pushback from a variety of fronts, with lack of trial participant diversity being one of them. Older Black and Hispanic Americans are 1.5 to 2 times as likely to have Alzheimer's or other dementias as older white Americans, according to the Alzheimer's Association.
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Biogen said the phase 1b study showed concentration of total-tau in the cerebrospinal fluid had decreased 30%, 40% and 49% eight weeks after the final dose in the low, medium and high dose groups, respectively. Those were given every four weeks, and a fourth dose was given every 12 weeks. All patients, 46 in total, completed the multiple ascending dose and three voluntarily withdrew from the post-treatment period.
Bernstein analysts wrote in a note that the results are "successful" given the treatment achieved the pharmacodynamic target and "suggest a (somewhat) clinically viable dosing regimen of quarterly intrathecal dosing." The analysts predict clinical data in mid-2022 as the open-label extension is slated to end in May 2022.
In their note, the Bernstein analysts predict a phase 2 proof-of-concept trial will begin before the end of this year and lead to a potential read out in late 2023.
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The analysts did not hold back. They pinned the odds of success "low" at this point. The silver lining? The asset is still a "very good test of the Tau hypothesis," the Bernstein analysts wrote.
"These study results support further investigation of BIIB080 for the treatment of Alzheimer’s disease and suggest that antisense-mediated suppression of tau protein may be a feasible therapeutic approach for other tauopathies,” said C. Frank Bennett, Ph.D., Ionis chief scientific officer and leader of the company's neurological programs, in a statement.
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Biogen's head of research and development, Alfred Sandrock, Jr., M.D., Ph.D., said in a statement that the results are encouraging and the company "looks forward" to more clinical studies for the asset.
The trial enrolled patients ages 50 to 74 with mild Alzheimer's who had confirmed amyloid positivity at screening. Part 1 was a multiple ascending dose study of 46 patients in a three-month treatment evaluation period followed by a six-month post-treatment period. Part 2 comprised an open-label long-term extension study consisting of 12 months of treatment evaluation and four or six months post-treatment.
Biogen and Ionis reported no serious adverse events in the trial's patients. The trial was conducted at sites in the UK, Sweden, Netherlands, Germany, Finland and Canada.