GTC Biotherapeutics (fka GTCB)

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MM-093 IS SAFE AND WELL TOLERATED IN AN EXPLORATORY PHASE 2 STUDY AND PATIENTS WITH THE HIGHEST SERUM LEVELS OF MM-093 ACHIEVED ROBUST CLINICAL RESPONSES


http://tinyurl.com/2zkgnj

J. Murray1, A. Sawitzke2
1Clinical, Merrimack Pharmaceuticals, Inc, Cambridge, 2Rheumatology, University of Utah, Salt Lake City, United States

Background: MM-093 is a non-glycosylated, recombinant version of human alpha-fetoprotein that is produced by recombinant DNA technology in a transgenic goat expression system. The purpose of this exploratory dose-ranging study was to evaluate the safety and efficacy of MM-093 in patients with moderate-severe RA despite current MTX therapy.

Methods: Adults with active RA [ ≥6 swollen joints; ≥6 tender joints]; ≥6 months’ duration of RA; and on stable MTX therapy were randomized to receive MM-093 (2.5mg, 7.5mg, 20mg) or placebo. Study drug was administered by the patient as a subcutaneous injection in their abdomen once a week for 6 months. A total of 259 patients were randomized at 39 centers in the United States. The primary endpoints were safety and efficacy as measured by ACR20 response. Secondary efficacy endpoints included DAS28-CRP and EULAR.

Results: MM-093 was safe and well tolerated across all dosing groups. The number of patients experiencing an adverse event (AE); the relationship of AE’s to study drug; and the severity of AE’s was similar between groups. There were no dose relationships in any of the lab analytes or in any of the clinically significant lab abnormalities. Additionally, there were no drug related SAE’s in the active groups and none of the patients had detectable limits of anti-MM-093 antibodies.

In the intent to treat population, there was a non-statistically significant improvement in ACR20 in the 20mg group versus placebo. The percentage of patients achieving a EULAR “good” + “moderate” response was statistically significant in the 20mg group versus placebo (p = 0.038) and there was a -1.6 improvement in the DAS28-CRP score from baseline in the 20mg group, compared to a -1.3 improvement in the placebo group.

In general, clinical responses increased as serum levels of MM-093 increased. In patients with the highest serum levels of MM-093 (i.e. >1600ng/ml), 7/9 achieved an ACR20, 8/9 achieved a moderate/good EULAR response and 6/9 had low disease activity or were in remission as measured by DAS28-CRP (See Table below).

Conclusion: In an exploratory dose-ranging study, MM-093 was safe and well tolerated. Patients with serum levels above 1600ng/ml showed a robust clinical response, suggesting that higher doses need to be tested in future trials with MM-093.