Although the study did not meet primary and secondary endpoints in patients with PSP, Biogen still plans to continue to study the drug for mild cognitive impairment in Alzheimer disease.
Alfred Sandrock Jr, MD, PhD
Top-line results from the phase 2 PASSPORT study of BIIB092 (gosuranemab; Biogen) failed to meet the primary and secondary endpoints in patients with progressive supranuclear palsy (PSP), leading to discontinuation of the trial.1
“We remain unwavering in our commitment to advancing therapies that have the potential to address the significant unmet medical needs of people with neurodegenerative diseases who are faced with limited to no treatment options,” Alfred Sandrock Jr., MD, PhD, executive vice president of Research and Development and chief medical officer at Biogen, said in a statement.1
The double-blind, placebo-controlled, parallel-group study of gosuranemab (NCT03068468) included 490 participants randomly assigned to either 50 mg of gosuranemab or placebo. Patients were administered 50 mg of gosuranemab through intravenous (IV) infusion once every 4 weeks for 48 weeks in the double-blind treatment period followed by a 50 mg dose of gosuranemab once every 4 weeks from weeks 52 to 208. Patients were assessed on change from baseline in the PSP Rating Scale (PSPRS) at week 52. Additionally, investigators measured frequency of deaths, serious adverse events (SAEs), adverse events (AEs) leading to discontinuation, and grade 3 and 4 laboratory abnormalities as a way to assess the safety and tolerability profile of gosuranemab.
At week 52, gosuranemab did not meet the primary endpoint of change from baseline in the PSPRS, showing no significant difference from placebo. The investigators noted that the safety results from the trial remained consistent with previous studies of gosuranemab.
Earlier this year at the 2019 International Congress of Parkinson’s Disease and Movement Disorders (MDS), September 22-26, in Nice, France, Biogen presented late-breaker data from the open-label, long-term study of gosuranemab in patients with PSP.2 Results showed that gosuranemab appeared to be well tolerated with an acceptable safety profile. In this study, patients received gosuranemab (150, 700 or 2100 mg) or placebo every 4 weeks for 12 weeks. Forty-seven of the 48 patients enrolled were included in anadditional open-label study (NCT02658916) that spanned 24 months and assessed safety parameters such as SAEs, AEs, laboratory tests, and ECG data.
Of the 47 participants assessed, 30 reached more than 96 weeks of gosuranemab exposure, while the overall median exposure was 750 days. Only 1 participant did not experience an AE. Common AEs included falls (n = 34), urinary tract infection (n = 23), and contusion (n = 19).Among the 22 SAEs, 11 occurred in the gosuranemab 2100 mg dose group. The most common SAE was death, which occurred in 4 patients, all in the gosuranemab 2100 mg dose group.
Biogen still plans to continue its phase 2 TANGO study (NCT03352557) of gosuranemab for mild cognitive impairment due to Alzheimer disease (AD). The ongoing trial includes 654 participants, age 50 to 80, who will be randomly assigned to receive a low dose, medium dose, or high dose of gosuranemab every 4 weeks or placebo. In addition, some participants will Others will receive a low dose of gosuranemab every 12 weeks and a placebo dose at the 4-week dosing visits.
The randomized, double-blind, placebo controlled, parallel-group study will assess the safety, tolerability, and efficacy of gosuranemab. Patients will be assessed for change from baseline in Clinical Dementia Rating Scale — Sum of Boxes score to week 78.Additionally, patients will undergo physical exams, including electrocardiograms and blood tests through week 90. The trial, which began in May 2018, is expected to conclude in March 2024.
1. Biogen reports top-line results from phase 2 study in progressive supranuclear palsy [news release]. Cambridge, MA. Biogen. December 13, 2019. globenewswire.com/news-release/2019/12/13/1960373/0/en/Biogen-Reports-Top-Line-Results-from-Phase-2-Study-in-Progressive-Supranuclear-Palsy.html. Accessed: December 13, 2019.
2. Kuperman J, Boxer A, Grundman M, et al. Safety results of an open-label, long-term treatment study of gosuranemab (formerally BIIB092) in participants with PSP. Presented at: 2019 International Congress of Parkinson’s Disease and Movement Disorders. September 22-26, 2019; Nice, France. Abstract LBA 11.