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Clinical Trials

Date: 2018-08-16

Type of information: Interim results

phase: 3

Announcement: interim results

Company: Regeneron Pharmaceuticals (USA - NY) Teva Pharmaceutical (Israel)

Product: fasinumab

Action mechanism:

  • monoclonal antibody. Fasinumab is a fully human monoclonal antibody against Nerve Growth Factor (NGF) that was designed to reduce pain sensitization in neurons. Preclinical experiments indicate that fasinumab specifically binds to NGF and blocks NGF activity, and that fasinumab does not bind to or block cell signaling for closely related neurotrophins (NT) such as NT-3, NT-4 or BDNF (brain-derived neurotrophic factor).
  • Regeneron and Teva are jointly developing fasinumab as part of a global collaboration agreement. In Japan and 10 other Asian countries, Mitsubishi Tanabe Pharma Corporation holds exclusive development and commercial rights for fasinumab.

Disease: moderate-to-severe osteoarthritis pain of the hip or knee

Therapeutic area: Rheumatic diseases - Inflammatory diseases

Country:

Trial details:

  • The Phase 3 study is a sub-study of a larger, long-term trial that involves 52 weeks of active treatment, designed to determine the safety and tolerability of fasinumab, including AEs of special interest, in patients with pain due to radiographically-confirmed OA of the knee or hip. Approximately 85% of sub-study patients had OA of the knee. The primary efficacy data were assessed at 16 weeks; the primary safety analysis of the larger long-term trial will occur at 72 weeks (52-week active treatment and 20-week follow-up periods).

Latest news:

  • • On August 16, 2018, Regeneron Pharmaceuticals and Teva Pharmaceutical Industries announced positive topline results from a Phase 3, randomized, double-blind, placebo-controlled study of fasinumab in patients with chronic pain from osteoarthritis (OA) of the knee or hip. At the week 16 primary efficacy analysis, the study met both co-primary endpoints and all key secondary endpoints. Fasinumab-treated patients experienced significantly less pain and significantly improved functional ability from baseline compared to placebo.
  • The study compared two different fasinumab treatment arms (subcutaneous 1 mg every four or eight weeks) with placebo. The co-primary endpoint results are presented in Table 1.
  • Table 1: Topline Efficacy Results from Phase 3 Study

Placebo

(n=214)

Fasinumab 1 mg every 8 weeks

(n=215)

Fasinumab 1 mg every 4 weeks

(n=217)

Change in pain at week 16 vs. baseline (least squares [LS] mean)2

-1.56

-2.25

(p=0.0019)

-2.78

(p < 0.0001)

Change in physical function at week 16 vs. baseline (LS mean)3

-1.37

-2.10

(p=0.0011)

-2.57

(p < 0.0001)

  • 1. Approximately 85% of sub-study patients had OA of the knee;
  • 2. As measured by the Western Ontario and McMaster Universities Osteorarthritis Index (WOMAC) pain subscale score (score range: 0-10);
  • 3. As measured by the WOMAC physical function subscale score (score range: 0-10)
  • After the primary efficacy assessment at week 16, patients continue on therapy for an additional 36 weeks, followed by a subsequent 20-week off study drug follow-up period for further safety assessment.
  • Interim safety data indicate that fasinumab was generally well tolerated, with similar adverse events (AEs) as those observed in previous fasinumab trials. At week 16, treatment discontinuations due to AEs had occurred in 6% of the placebo group patients, 5% of the fasinumab 1 mg every eight weeks group patients and 6% of the fasinumab 1 mg every four weeks group patients. The fasinumab safety program was designed to capture all arthropathies (joint damage), including those identified due to symptoms and those identified by regularly-scheduled radiographic monitoring, the first of which was scheduled at week 24. Among the approximately 65% of patients who had completed their first radiographic assessment, the placebo-adjusted rate of adjudicated arthropathies was approximately 2%. The majority of arthropathies were captured by the regularly-scheduled radiographic monitoring and involved isolated joint space narrowing, called RPOA-1 (rapid progressive OA type 1). No cases of osteonecrosis have been identified to date in this study.
  • The safety data presented here are interim data and preliminary in nature. Earlier this year, an Independent Data Monitoring Committee (IDMC) monitoring the safety and efficacy of ongoing fasinumab trials recommended that the two higher dose regimens (3 mg every four weeks and 6 mg every eight weeks) be discontinued.
  • The companies plan to present detailed results at an upcoming medical congress.
   

Is general: Yes