- Merck and Pfizer touted positive trial results for the jointly developed SGLT-2 inhibitor ertugliflozin at the American Diabetes Association conference, announcing two combinations pairing the type 2 diabetes drug with metformin or Merck's blockbuster Januvia (sitagliptin) helped improve blood glucose control in separate Phase 3 studies.
- The two pharmas have three New Drug Applications under review by the Food and Drug Administration for ertugliflozin and the combinations of the drug with metformin and Januvia, respectively. Decisions on all three are expected by December of this year, but even with a clean sweep ertuglizflozin would be the fourth SGLT-2 inhibitor approved.
- J&J's Invokana (canagliflozin) and AstraZeneca's Farxiga (dapagliflozin) are the current market leaders in a class that is expected to grow further. But proving a cardiovascular benefit has become the next hurdle to clear after Eli Lilly and Boehringer Ingelheim's Jardiance (empagliflozin) demonstrated a cardio-protective effect in the landmark EMPA-REG study.
While Merck and Pfizer hit on both Phase 3 studies testing ertugliflozin, the two will have their work cut out to successfully differentiate the SGLT-2 inhibitor — if approved later this year — from the three existing options on the market.
In addition to Jardiance's already proven cardiovascular benefit, J&J and AstraZeneca both have outcomes studies underway that could further raise the barrier to entry for a drug like ertugliflozin.
Results from J&J's trial, called CANVAS, are expected to be announced later today from the American Diabetes Association conference in San Diego. AstraZeneca has its own large outcomes study, dubbed DECLARE, under way, aimed at showing a cardioprotective benefit to Farxiga. Full results from that study are expected in 2019 at the latest.
Concurrent with the announcement of ertugliflozin's study successes, Merck and Pfizer also said a cardiovascular study for the drug completed enrollment with approximately 8,000 patients. Estimated study completion is late 2019, according to clinicaltrials.gov.
In Merck and Pfizer's two studies, ertuglifozin showed a competitive ability to lower A1C, a commonly used measure of average blood glucose in diabetes patients. When added to metformin, treatment with ertugliflozin resulted in a 0.7% and 0.9% reduction in A1C levels at the 5 mg and 15 mg doses, compared to 0.0% for placebo plus metformin.
The second trial, pairing ertugliflozin with Januvia, showed a greater than 1.6% and 1.7% A1C lowering at the two respective dose levels, compared to 0.4% for placebo and Januvia.
In both cases, a substantially greater proportion of patients reached the benchmark A1C treatment goal of less than 7.0% than those in the placebo arms.
Even in a competitive SGLT-2 class, ertugliflozin's performance could help Merck bolster its Januvia franchise. With Januvia, Merck currently has a dominant market share in the DPP-4 class of diabetes drugs. Sales slowed somewhat in the first quarter, although Merck chalked that up to the effect of customer stocking. Approval of a Januvia/ertugliflozin combo could help extend the life of Januvia and slow sales erosion.
Still, a more restrictive payer environment, coupled with strong competition, could make for a slow ramp-up for ertugliflozin, if approved.
J&J reported a sales decline of nearly 13% in the first quarter for Invokana, mostly due to performance in the U.S. where the pharma giant flagged higher discounts and a greater proportion of treated patients covered under Medicaid.
AstraZeneca notched 2% sales growth for Farxiga over the same period, but also noted a "subdued" environment due to managed-care access and affordability programs.
Following EMPA-REG, positive cardiovascular results from CANVAS could help support earlier use of SGLT-2 inhibitors as a class, but would also raise the stakes for Farxiga and ertugliflozin to also hit on their respective outcomes studies down the road.