Merck, Pfizer amp up ertugliflozin outcomes study as SGLT2 med scores in PhIII

Merck Pfizer combo

NEW ORLEANS--Merck & Co. and Pfizer are doubling down on their ertugliflozin cardiovascular outcomes study as rival SGLT2 med Jardiance continues to generate buzz for its recent score in a heart-safety test.

The development partners are now looking to enroll 8,000 patients with Type 2 diabetes and established vascular disease, and they added two secondary endpoints--cardiovascular death and a composite endpoint covering CV death and hospitalization for heart failure.

The study started as a 4,000-patient trial focused on cardiovascular safety, Dr. Peter Stein, VP of late-stage development in diabetes and endocrinology, told FiercePharma. "We are expanding it further so we can properly power it to measure a cardiovascular benefit," Stein explained. The Jardiance CV benefits drummed up new excitement about outcomes trials, and Merck and Pfizer "are very excited to be part of that," he said.

News of the expanded outcomes trial came along with data from two pivotal studies, in which ertugliflozin hit its blood-sugar goals. In one, the single drug topped placebo at lowering A1C, a key measure of blood glucose, and in the other, a combo with Januvia beat that drug alone at the same task.

Outcomes trials are increasingly important as doctors weigh newly launched drugs and payers consider whether to cover them. In its big EMPA-REG outcomes trial, Eli Lilly ($LLY) and Boehringer Ingelheim’s Jardiance reduced cardiovascular risks compared with placebo, becoming the first diabetes drug to achieve that feat. Since then, Novo Nordisk ($NVO) rolled out top-line data on its GLP-1 med Victoza, showing that it, too, cut the risk of cardiovascular complications in diabetes patients.

New data from both of those trials--EMPA-REG and the Novo trial, LEADER--will be presented in the next few days at ADA. The primary endpoint in Merck ($MRK) and Pfizer's ($PFE) outcomes trial is still a non-inferiority test of ertugliflozin against placebo on a common composite CV endpoint comprising CV death, heart attack and stroke.

Merck and Pfizer’s outcomes trial news comes along with data from two Phase III ertugliflozin trials. In the first, a 5-mg ertugliflozin dose cut A1C by 0.99% compared with placebo, and a 15-mg dose beat placebo with a 1.16% reduction. More patients on ertugliflozin also hit an A1C goal of 7%, at 28.2% and 35.8%, compared with 13.1% for placebo.

In the other study, ertugliflozin combined with Januvia beat Merck’s blockbuster DPP-4 drug alone. Adding the SGLT2 drug to Januvia achieved an A1C reduction of 1.5% at both the 5-mg and 15-mg ertugliflozin doses, compared with 1% for that drug alone and 1.1% for a 100-mg dose of Januvia alone.

The potential for a Januvia combination is one reason why Merck jumped into the SGLT2 field, Stein said: "Januvia is a go-to drug that doctors are comfortable with, and it's exciting to have a new SGLT2 with a different profile and potentially complementary mechanism."

More than half of patients taking 5 mg of ertugliflozin plus Januvia hit their 7% A1C goal--results that Stein called "exciting"--and almost half of the patients taking 15 mg did. The biggest percentage of patients taking any of the single-drug regimens to achieve that goal was 32.8% for Januvia.

Merck and Pfizer plan to submit ertugliflozin for FDA approval by the end of this year, along with two combo meds: one that pairs ertugliflozin with the standard diabetes therapy metformin, another that married ertugliflozin with Januvia. The company plans more trials with different combinations, as well as some comparative studies, Stein said.

The suite of ertugliflozin-based products would hit the market after several other SGLT2 singles and combos. There’s Lilly and Boehringer’s Jardiance, of course, but also Johnson & Johnson’s ($JNJ) first-to-market Invokana and its metformin combo Invokamet, and AstraZeneca’s ($AZN) Farxiga. A Farxiga combo, which pairs the drug with AstraZeneca’s DPP-4 med Onglyza, was turned back by the FDA in October. The agency asked for additional clinical data, delaying the two-in-one med by at least 8 to 10 months, analysts said, and perhaps a couple of years.

- see the release from Merck and Pfizer

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