This article first appeared in MedPage Today (http://www.medpagetoday.com/meetingcoverage/mds/65883)
by Kristina Fiore, Deputy Managing Editor, MedPage Today
June 08, 2017
VANCOUVER — Two companies are working on anti-tau monoclonal antibodies for progressive supranuclear palsy (PSP), although one withdrew its phase I results just ahead of the scheduled presentation at the Movement Disorder Society meeting here.
AbbVie’s ABBV-8E12 and Bristol-Myers Squibb’s BMS-986168/BIIB092 — rights to which were recently licensed to Biogen — both proved safe and well-tolerated in phase I studies, and both have moved into phase II trials, according to the companies.
But an MDS press release featuring the BMS/Biogen drug was pulled from the conference website because the authors withdrew the study at the last minute, according to an MDS spokesperson.
Catherine Falcetti, a spokesperson for Biogen, blamed the licensing deal: “The transition from BMS to Biogen took place days before the meeting, thus the decision to postpone the presentation.”
Biogen announced in April that it would pay BMS $300 million up-front plus potential milestone payments and royalties for rights to the drug.
BMS-986168/BIIB092 is a monoclonal antibody that targets extracellular tau (eTau), and according to the original MDS press release, it was safe and well tolerated in PSP, with good target engagement as evidenced by significant suppression of free eTau in cerebrospinal fluid (CSF).
The phase I trial, conducted by Irfan Qureshi, MD, of Albert Einstein College of Medicine in New York, and colleagues enrolled 48 patients who were given ascending doses of the antibody as intravenous infusions every 4 weeks over 3 months.
Falcetti noted that the first patient has been dosed in the phase II study.
Nuno Mendonca, MD, a medical director for AbbVie in Germany, presented phase I findings for ABBV-8E12, in which 30 patients with PSP were randomized 3:1 to receive placebo or various intravenous doses of the drug (2.5, 7.5, 15, 25, or 50 mg/kg).
The drug was safe and well tolerated, with 70% of patients experiencing adverse effects, the majority of which were rated as mild (75%) or moderate (21%). There were three serious adverse events, one each in the 15-, 25-, and 50-mg/kg cohorts. There was one discontinuation in the subject in the 25-mg/kg group that had an increase in agitation/anxiety and had a prior history of both. There was a subdural hematoma in the 15-mg/kg group and hypertension with 50 mg/kg, but this was determined unrelated to treatment given the patient’s history of hypertension.
Mendonca said the phase II ARISE trial in PSP is currently recruiting its target of 180 patients who’ve had the disease for less than 5 years. The primary endpoint will be change in PSP Rating Scale score from baseline to one year.
“The current thinking is that the misfolded protein tau is behind the disease, so it’s a pure tauopathy,” Mendonca told MedPage Today, suggesting that removing the aberrant tau could impact the disease course.
In the withdrawn press release about the BMS/Biogen drug, Werner Poewe, MD, of Medical University Innsbruck in Austria, noted that immunotherapies targeted at tau, “which plays a key role in PSP, have shown promising results in transgenic mouse models of this disorder in terms of reducing tau concentrations and neuronal pathology.”
“These results provide important additional support for the concept of anti-tau immunotherapy with monoclonal antibodies in PSP,” Poewe added.
PSP is a progressive neurodegenerative disease characterized by the deposition of tau and neurofibrillary tangles in several areas of the nervous system. It affects 20,000 people in the U.S. and the median survival after symptom onset is 7 years. Currently, there are no disease-modifying therapies available.
Given the role of tau in Alzheimer’s disease, anti-tau monoclonal antibodies are also being investigated in that condition. Mendonca told MedPage Today that Abbvie is currently recruiting 400 patients with early Alzheimer’s disease and a positive amyloid PET scan into a 96-week trial. The primary endpoint will be change on the Clinical Dementia Rating-Sum of Boxes (CDR-SB).
“In Alzheimer’s, we know that beta-amyloid seems to be the trigger for what then becomes a tauopathy,” he said. “It seems to be more directly correlated with what happens in the disease. So removing it may be a good opportunity to halt progression of the disease.”
Biogen has also expressed interest in developing its anti-tau candidate for Alzheimer’s.