Merck & Co.'s Midas Touch Continues as Heart Drug Succeeds Where Pfizer, Eli Lilly and Roche's Failed
June 27, 2017
By Mark Terry, BioSpace.com Breaking News Staff
Kenilworth, NJ – Merck announced that its Phase III REVEAL trial of anacetrapib met its primary endpoint, significantly cutting major coronary events compared to placebo.
On the surface, that would appear to be great news. However, at least two things garnered attention in the company’s announcement. First, it said it was going to review the trial data with external experts before or if it was going to file a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA). And secondly, in what is unusual for these types of releases, there was no quote provided by a company executive.
Umer Raffat, an analyst with Evercore ISI, wrote in a research note, “Buyside was NOT expecting this Merck trial to ‘work’…”
Seamus Fernandez, an analyst with Leerink, also spent some time parsing the Merck press release for what it did and did not say, noting that the “cryptic language in the press release suggests a less than definitive risk/reward profile of the drug.”
John Carroll, writing for Endpoints News, says, “Heart disease R&D, though, has become a much changed field over the last few years, as new PCSK9 cholesterol drugs have proved. Amgen recently tried to grab a market lead with its positive outcomes data, but so far has gained little traction among payers who were unconvinced by the numbers. And significantly, Merck’s short statement notes that the giant player is still considering whether to file for an approval, leaving everyone eager to see the hard data at the European Society of Cardiology meeting August 29.”
Anacetrapib is an investigational cholesteryl ester transfer protein (CETP) inhibitor. The REVEAL study, which stands for Randomized Evaluation of the Effects of Anacetrapib through Lipid modification, evaluated 30,000 patients over at least four years. It was used to assess the efficacy and safety of adding anaceptrapib to a statin medication, Lipitor (atorvastatin).
The trial was designed and independently conducted by the Clinical Trial Service Unit (CTSU) at the University of Oxford in collaboration with the TIMI Study Group at Brigham and Women’s Hospital in Boston, and with Merck. Merck provided the funding.
Forbes notes, “Whereas many recent heart drug trials have looked at only heart attacks, strokes, and cardiovascular deaths, Merck’s study also included stenting procedures to open blocked arteries. Exactly what the drug prevented will be important. Also, anacetrapib has a liability: the molecule stays in the body, in fat tissue, for years after patients take it. That could make the drug more effective, but it also means that any side effects could last even after patients stop taking the drug.”
One of the surprises of the trial is that a CETP inhibitor worked at all. Pfizer , Eli Lilly and Roche have all had failures with CETP inhibitors. Many analysts and scientists thought the category was a dead end.
Pfizer’s CETP inhibitor combined with Lipitor increased the rate of death, and increased blood pressure. Roche licensed its from Japan Tobacco, and in 2012, halted a 15,000-patient study because it didn’t seem to have a positive effect on LDL. Lilly scrapped its CETP inhibitor in 2015 because of a lack of efficacy.
Sekar Kathiresan, director of the Center for Genomic Medicine at Massachusetts General Hospital, tweeted, “It’s a shock. Where else have three drugs in a class failed in large-scale [randomized controlled trials] but the fourth succeeds! Drug development is a tough business.”