Setback for Merck's BTK Inhibitor Evobrutinib in Phase III Trials for Multiple Sclerosis
Merck Group
Pharmaceutical R&D Developer
Since its debut in 2013, the BTK inhibitor ibrutinib has been rapidly advancing.
The strong money-making ability of BTK inhibitors has attracted many players to enter the field, with hundreds of BTK inhibitors currently in the research and development stage.
Of course, not all BTK inhibitors are crowded in the hematological tumor field. Some pharmaceutical companies are attempting to rebuild the order of BTK inhibitors in the autoimmune disease arena.
However, the development of innovative drugs has always been challenging. This year, in the exploration of BTK inhibitors for autoimmune diseases, there has been Novartis' success, but also Merck KGaA's failure.
On December 6, Merck announced that the BTK inhibitor Evobrutinib did not demonstrate sufficiently good efficacy in two final-stage studies targeting patients with relapsing multiple sclerosis. Affected by this news,Merck's Stock Price Plummets.
What impacts will this bring?
/ 01 /
The Loss of the Leader
BTK, as a key kinase in the B-cell receptor signaling pathway, plays an important regulatory role in immune cells involved in the pathogenesis of multiple sclerosis, such as B lymphocytes, macrophages, and microglia.
Therefore, BTK inhibitors are expected to provide novel therapeutic options for autoimmune diseases such as multiple sclerosis.
Globally, there are already three products in Phase III clinical stage, which are Merck's Evobrutinib, Sanofi's Tolebrutinib, and Roche's Fenebrutinib, respectively.
Unfortunately, Evobrutinib has brought a message of failure first.
According to the announcement by Merck, the two Phase III EVOLUTION clinical trials showed that Evobrutinib had no advantage over oral teriflunomide in reducing the annual relapse rate in patients with relapsing multiple sclerosis.
The poor efficacy undoubtedly brings more uncertainties to the development of BTK inhibitors in the field of multiple sclerosis.
Prior to this, the shadow of liver injury caused by BTK inhibitors has been lingering. In April this year, the FDA partially placed clinical holds on Merck KGaA's Evobrutinib due to concerns about liver injury it may cause in Phase III studies for multiple sclerosis.
Apart from Merck, other companies including Sanofi, Norvatis, and domestic enterprises such as InnoCare Pharma have also encountered this issue.
Nowadays, while safety issues still need to be explored, efficacy issues have become a new challenge that all companies must consider.
/ 02 /
The Journey of Self-Immunity Continues
Of course, this does not mean that the exploration of BTK inhibitors in the autoimmune field has come to a halt.
In fact, after a series of BTK inhibitor challenges in autoimmune diseases ended in failure, this field has also welcomed a long-awaited victory this year.
On August 9, Novartis announced that its BTK inhibitor Remibrutinib had met all primary and secondary endpoints in the two Phase III studies, REMIX-1 and REMIX-2, namely, the absolute change from baseline in the weekly urticaria activity score (UAS7) at week 12.
Remibrutinib is a covalent irreversible BTK inhibitor with very high selectivity, which can rapidly bind to the inactive conformation of BTK to achieve long-term inhibition. Unbound drug is cleared from the body, reducing systemic exposure and minimizing toxic side effects.
Perhaps the unique structure of Remibrutinib determines its better safety.
As early as April this year, Novartis indicated that its BTK inhibitor might not encounter the same safety issues as its competitors' products. So far, no signs of liver damage have emerged in its clinical trials. The positive news brought by Remibrutinib also demonstrates its advantage in terms of safety.
This further tells the market that there is still room for exploration in the field of BTK inhibitors for treating autoimmune diseases, and safety issues are not an insurmountable threshold.
Although Merck faced setbacks in the multiple sclerosis field, the journey of BTK inhibitors in autoimmune diseases will continue.
Text by Cai Jiu
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