Date: 2015-10-29
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the 2015 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) being held in Indianapolis
Company: Alkermes (Ireland)
Product: ALKS 8700 (monomethyl fumarate)
Action
mechanism: ALKS 8700 is an oral, novel and proprietary monomethyl fumarate (MMF) molecule in development for the treatment of multiple sclerosis (MS). ALKS 8700 is designed to rapidly and efficiently convert to MMF in the body and to offer differentiated features as compared to the currently marketed dimethyl fumarate, Tecfidera®.
Disease: multiple sclerosis
Therapeutic area: Neurodegenerative diseases
Country:
Trial details:
Latest
news: * On October 29, 2015, Alkermes provided an update on its regulatory strategy and positive clinical trial results for ALKS 8700, a novel, oral monomethyl fumarate (MMF) molecule in development for the treatment of multiple sclerosis (MS). ALKS 8700 is designed to rapidly and efficiently convert to MMF in the body and offer differentiated features as compared to the currently marketed dimethyl fumarate, Tecfidera®. Based on a meeting with the FDA, Alkermes plans to file a 505(b)(2) New Drug Application (NDA) using pharmacokinetic bridging data from studies comparing ALKS 8700 and Tecfidera®, as well as a two-year phase 3 safety study of ALKS 8700 in approximately 600 patients with MS. Importantly, this means that Alkermes will not be required to conduct a separate phase 3 efficacy study in patients with MS. In addition, Alkermes intends to initiate a randomized, head-to-head study comparing the gastrointestinal (GI) tolerability of ALKS 8700 and Tecfidera® in approximately 420 patients with MS in mid-2016. Alkermes expects to complete these studies and file the NDA in 2018. Clinical update: Alkermes recently completed a randomized, double-blind phase 1 comparative pharmacokinetic study evaluating plasma MMF levels achieved by administration of single doses of ALKS 8700 and Tecfidera®. Initial data from this study showed that ALKS 8700 met the pharmacokinetic criteria for bioequivalence to Tecfidera®. The most common adverse events (AEs) in the study were flushing, dizziness and constipation for ALKS 8700, and flushing, nausea and diarrhea for Tecfidera®. Based on these results, Alkermes has selected the ALKS 8700 dose to be used in the registration program. Alkermes will need to conduct additional preclinical studies and pharmacokinetic studies to further support pharmacokinetic comparability to Tecfidera®. * On May 29, 2015, Alkermes announced that data from its phase 1, randomized, double-blind clinical study of ALKS 8700, a novel monomethyl fumarate (MMF) molecule in development for the treatment of multiple sclerosis (MS), is scheduled to be presented at the 2015 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) being held in Indianapolis, Ind. , May 27-30, 2015 . ALKS 8700 is designed to rapidly and efficiently convert to MMF in the body and offer differentiated features as compared to the currently marketed dimethyl fumarate, Tecfidera®. The study evaluated the safety, tolerability and single-dose pharmacokinetics (PK) of oral formulations of ALKS 8700 compared to both placebo and active control groups in healthy volunteers. Data from the study showed that ALKS 8700 was generally well tolerated and provided MMF exposures comparable to Tecfidera®, with less variability and favorable gastrointestinal (GI) tolerability. The most common adverse events (AEs) were flushing and GI-related. Based on the positive results from the study, Alkermes plans to advance ALKS 8700 with twice-daily dosing into pivotal development in 2015. * On February 9, 2015, Alkermes announced positive topline results from a phase 1, randomized, double-blind clinical study of ALKS 8700, a novel monomethyl fumarate (MMF) molecule in development for the treatment of multiple sclerosis. The study evaluated the safety, tolerability and single-dose pharmacokinetics (PK) of several oral formulations of ALKS 8700 compared to both placebo and active control groups in 104 healthy volunteers. Data from the phase 1 study showed that ALKS 8700 was generally well tolerated and provided MMF exposures comparable to Tecfidera®, with less variability and improved gastrointestinal (GI) tolerability. The most common adverse events (AEs) were flushing and GI-related. Based on the positive results from the study, Alkermes will request a meeting with the FDA, and plans to advance ALKS 8700 with twice-daily dosing into pivotal development in 2015. The three-part, randomized, double-blind phase 1 study was conducted in 104 healthy subjects. Part 1 was a single-ascending-dose, placebo-controlled design in 56 subjects to evaluate the safety, tolerability and PK of a range of single doses of ALKS 8700, and determine a dose that would provide MMF exposure comparable to 240 mg Tecfidera®, to be used in Part 2. Part 2 was a two-treatment, two-period crossover design in 16 subjects that compared the PK and tolerability of a single dose of ALKS 8700, 240 mg Tecfidera® or placebo. Part 3 included 32 subjects and evaluated PK of extended-release formulations of ALKS 8700. In Part 1, doses of ALKS 8700 ranging from 49 mg to 980 mg were evaluated. ALKS 8700 was rapidly converted to MMF, a dose-exposure relationship was observed, with higher MMF exposure associated with increasing ALKS 8700 dose levels, and a dose of ALKS 8700 providing MMF plasma exposure comparable to 240 mg Tecfidera® was identified for Part 2. In Part 2, subjects on active drug received either the selected dose of ALKS 8700 from Part 1 or 240 mg Tecfidera®, followed by the other agent on a subsequent day, thereby enabling a crossover comparison of PK and tolerability within the same subjects. In this part of the study, subjects who received ALKS 8700 demonstrated less variability in MMF exposure than subjects who received Tecfidera®, with a significantly lower maximum plasma concentration (Cmax). The percentage of subjects with GI-related AEs was lower with ALKS 8700 (8.3%) compared to Tecfidera® (41.7%). In Part 3, the PK data of the extended-release formulations of ALKS 8700 provided new insights into approaches for once-daily dosing options, which Alkermes will continue to pursue. Throughout the study, all dose levels of ALKS 8700 were generally well tolerated. The most common AEs were flushing and GI-related; all AEs were mild or moderate in severity. No serious AEs or discontinuations due to AEs were observed for ALKS 8700 in the study. Alkermes will present safety and PK data from the phase 1 study at an upcoming medical meeting and submit the results for publication in a peer-reviewed journal. * On July 17, 2014, Alkermes announced the initiation of a phase 1 clinical study of ALKS 8700, a novel monomethyl fumarate (MMF) molecule in development for the treatment of multiple sclerosis (MS). The randomized, double-blind study will evaluate the safety, tolerability and pharmacokinetics of several oral formulations of ALKS 8700 compared to both placebo and active control groups in approximately 125 healthy volunteers. ALKS 8700 is designed to rapidly and efficiently convert to MMF in the body and offer differentiated features as compared to the currently marketed dimethyl fumarate, Tecfidera®. This phase 1 study will investigate the pharmacokinetics and pharmacodynamics of multiple formulations and doses of ALKS 8700, and is designed to determine those suitable to progress into advanced clinical testing. The initiation of the phase 1 study follows Alkermes\' filing of an Investigational New Drug (IND) application with the FDA, and the issuance of a composition of matter patent for ALKS 8700 from the United States Patent and Trademark Office (USPTO) in March 2014 , which is expected to provide patent protection into 2033.
Recent Phase 1 Study Design and Results: This phase 1, randomized, double-blind clinical study evaluated the safety, tolerability and single-dose pharmacokinetics (PK) of ALKS 8700 compared to active control in 35 healthy volunteers. In this two-treatment, two-period crossover design, subjects received a single dose of either ALKS 8700 or Tecfidera®, followed by the other agent in the subsequent treatment period, thereby enabling a crossover comparison of PK and tolerability within the same subjects. Initial data from this study showed that ALKS 8700 met the pharmacokinetic criteria for bioequivalence to Tecfidera®.
The most common AEs in the study were flushing, dizziness and constipation for ALKS 8700, and flushing, nausea and diarrhea for Tecfidera®. No serious AEs or discontinuations due to AEs were observed in the study. Alkermes will present safety and PK data from the phase 1 study at an upcoming medical meeting and submit the results for publication in a peer-reviewed journal.
