Immediate release formulation of investigational MS therapy has optimal results

Key takeaways:

• An analysis of BIIB091 in various formulations and doses included 47 healthy volunteers.
• Administration twice per day of 250 mg immediate release tablets provided optimum results.

Treatment with immediate release tablets of a non-covalent Bruton’s tyrosine kinase inhibitor for relapsing forms of multiple sclerosis met pharmacokinetic and pharmacodynamic goals, data show.

“BIIB091 is a highly selective, potent, reversible and non-covalent Bruton’s tyrosine kinase inhibitor being developed for treatment of relapsing forms of multiple sclerosis,” Diana Gallagher, head of Biogen’s MS and Immunology Development Unit, told Healio in an email. The study was presented at ECTRIMS 2023.

Lead study author Hui-Hsin Tsai, PhD, associate medical director at Biogen, and colleagues sought to explore several formulations and treatment regimens of BIIB091 to enhance pharmacokinetic strength and achieve a steady state trough level (Ctrough) of > 221 ng/mL while limiting the drug exposure for those with relapsing-remitting MS.

They first analyzed data from 18 healthy volunteers given modified release (MR) tablets of the investigational therapeutic in five sequential dosing periods, with the ability to alter doses (50 mg to 500 mg) and in vitro release rate (80% in 2 to 12 hours) with BIIB091 crystalline active pharmaceutical ingredients and a spray dried dispersion MR tablet (250 mg, 80% release at 12 hours). Subsequently, 19 healthy volunteers were dosed in four sequential periods receiving immediate release (IR) tablets across varied dosing regimens as well as in both fed and fasting states. Multiple dosing and PD effects of the selected IR tablet regimen were then assessed in 10 healthy volunteers.

Results showed that the MR tablets did not meet the primary outcome Ctrough target, suggesting that absorption of BIIB091 was limited to the upper gastrointestinal tract, the researchers wrote. Tsai and colleagues then tested two doses of 250 mg (fasted) and 350 mg (with moderate fat [MF] meals) IR tablets 12 hours apart, which provided geomean C24 of 282 and 411 ng/mL, respectively.

Multiple dosing with 250 mg IR tablets twice per day in the MF fed state had geomean steady state Ctau of 407 ng/mL, with 9 of 10 volunteers achieving target Ctrough (221 ng/mL) and maintaining > 90% inhibition of CD69 expression on B cells during the 7-day treatment period. This formulation and dose would be subsequently tested in a planned phase 2 clinical trial.

“Since BIIB091 is highly selective and binds to BTK non-covalently, it may potentially have a lower risk of drug induced liver injury than covalent BTKs,” Gallagher said.

Editor's Note: The article was updated to clarify the formulation of BIIB091 as tablets and not capsules.