Merck - Arcoxia: Nice try but no MEDAL yet!

Arcoxia (etoricoxib) was to be Merck's follow-up to Vioxx.

"After four years of conducting this arthritis study program in more than 34,000 patients, we are looking forward to sharing the full MEDAL Program results in the future," said Dr. Peter S. Kim, president, Merck Research Laboratories.

Yeah, right. Sure thing Peter.

As Forbes say:

"The Arcoxia results will represent yet another minefield for Merck, now operating under the shadow of more than 11,000 Vioxx lawsuits that could cost it many billions of dollars. Even if the giant study, called MEDAL, shows no link between Arcoxia and heart problems, critics are likely to claim the study was designed in a way that hides the drug's risks.

But with no other study of a Vioxx-like drug's heart risk expected for at least three years, researchers who are hungry for leads as to why and how arthritis drugs lead to heart problems are likely to pore over the data."

The MEDAL Program was a prospectively designed clinical program combining CV safety data from three trials - the MEDAL, EDGE and EDGE II studies.

The MEDAL study, the longest of the three studies, was an event-driven CV outcomes study that included data in more than 23,000 OA and RA patients. The primary hypothesis of the MEDAL Program was that in the treatment of patients with OA and RA, Arcoxia 60 or 90 mg would be non-inferior or "no worse than" diclofenac 150 mg daily based on confirmed thrombotic CV events.

Thus, Arcoxia met its main goal of causing no more blood clot-related heart attacks than diclofenac, but more patients taking Arcoxia withdrew from the trial due to serious side effects. According to this preliminary analysis, the incidence of patients withdrawing from the trial due to side effects related to high blood pressure, edema and congestive heart failure was significantly higher for Arcoxia than for diclofenac.

Why diclofenac?

Unfortunately, there is a "distinct possibility" that MEDAL will not give any clear answers about the Cox -2 drugs and cardiovascular risk, according to Steven Nissen, a Cleveland Clinic cardiologist who was one of Vioxx's earliest critics.

Nissen frets that Merck is comparing Arcoxia to diclofenac, a drug that itself is thought to be a Cox-2 inhibitor that poses some cardiovascular risk.

In the lab, it behaves much like Celebrex. Moreover, he says, the MEDAL study takes into account not only heart attacks, strokes and cardiovascular events, but also clots in the veins and lungs, which might not be the result of Cox-2 drugs at all.

To further cloud the matter, heart attacks and other cardiovascular problems will only be counted in the first 14 days after patients stop their painkiller. In an editorial in the American Heart Journal, where the MEDAL design was recently published, Curt Furberg of Wake Forest University wrote that there is "no scientific support" for handling the data in this way. Furberg also wrote that the safety data on Celebrex are "disturbing."

So, the devil will lie in the details. And we await the "picking over" of the detailed data, once it has been revealed!