Results

Merck KGaA posts mixed data from their big PhIIb MS study on evobrutinib — spurring plenty of questions

Merck KGaA is posting some of their mid-stage data from a trial of their BTK inhibitor evobrutinib for multiple sclerosis. But despite a bold boast that the drug represents just how innovative their in-house R&D group is, the data are distinctly mixed.

On the primary endpoint, researchers claimed a clear win for the once-daily dose of 75 mg topping out with a statistically significant p value of 0.0015 in reducing the number of lesions measured among patients in the drug arm. The twice daily dose came in at 0.03 while the low dose failed. That’s not unusual.

But the therapy also fell well short of statistical significance for a key secondary: the annualized relapse rate (ARR), though the company claimed the results were “clinically relevant” — always a rich field for dispute.

A reduction in ARR was seen with evobrutinib 75mg QD (0.13; p=0.09) and 75mg BID (0.08; p=0.06) versus placebo (0.37), with evidence of a dose-response relationship.

According to clinicaltrials.gov, this study also included a Tecfidera comparator arm, to give researchers a look at a market leader from Biogen. But their statement says the Tecfidera arm “represented an open-label reference arm, and there were no formal statistical comparisons between dimethyl fumarate and evobrutinib or placebo.”

In a followup with a Merck spokesperson on Tecfidera’s open-label numbers, I got this back:

Mean total T1 Gd+ lesions at Weeks 12-24 (SD) were 1.15 (3.70), 1.69 (4.69), 4.06 (8.02) and 3.85 (5.44) for evobrutinib 75 mg BID, 75 mg QD, 25 mg QD and placebo, respectively. In the same timeframe, mean total T1 Gd+ lesions were 4.78 (22.05) for (Tecfidera) dimethyl fumarate (reference arm).

Unadjusted annualized relapse rate (ARR) was 0.08, 0.13, 0.57 and 0.37 for evobrutinib 75 mg BID, 75 mg QD, 25 mg QD and placebo, respectively. The unadjusted ARR for dimethyl fumarate (Tecfidera) was 0.22 (reference arm).

Merck KGaA has gone through a grueling decade, looking to regain a rep for drug development it lost during a lengthy clinical drought. This drug represents a major investment on their part, coming out of their in-house R&D ops with other studies going for lupus and rheumatoid arthritis.


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