Merck and Pfizer’s Steglatro, late to the SGLT2 party, has been working to catch up to its in-class rivals, which already bear heart-helping approvals. But its cardiovascular outcomes data won’t help it get on their level.
Steglatro showed it could match placebo when it comes to the combined rate of heart attack, stroke and cardiovascular death among high-risk Type 2 diabetes patients, satisfying an FDA requirement to show it’s not a threat to heart safety.
In each arm, 11.9% of patients suffered one of those cardiovascular events, the companies said Tuesday at the American Diabetes Association’s virtual annual meeting.
But while the results may show that Steglatro is safe, the drug is still lacking what competitors Jardiance from Eli Lilly and Boehringer Ingelheim; Invokana from Johnson & Johnson; and Farxiga from AstraZeneca already have: outcomes data showing they can ward off major CV events.
Jardiance was the first to produce that type of data and followed up by scoring an FDA nod to decrease the risk of cardiovascular death among high-risk Type 2 diabetes patients. Invokana came next with clearance to reduce the risk of major CV events in that same population, and, more recently, it also picked up a go-ahead to treat chronic kidney disease (CKD) and reduce the risk of hospitalization for heart failure in patients with Type 2 diabetes and CKD.
Farxiga, meanwhile, bears approvals to reduce the risk of hospitalization for heart failure in high-risk Type 2 diabetes patients as well as to cut the risk of cardiovascular death and hospitalization for heart failure in patients with a reduced ejection fraction, regardless of whether they have diabetes.
Merck and Pfizer's trial, dubbed Vertis CV, “was expanded when it became evident that there were some other potential benefits that were seen with SGLT2 inhibitors,” Sam Engel, M.D., Merck’s associate vice president of clinical research for diabetes and endocrinology, said.
Unfortunately for Merck and Pfizer, Steglatro also missed on all the key secondary endpoints from the trial. The drug didn't prolong the time to cardiovascular death or hospitalization for heart failure, nor did it ward off a group of kidney problems, including death and dialysis.
Why the struggle in an area where its competition has succeeded? It's tough to say, Engel said.
"It's always difficult to compare across studies because of differences in study design, study population, even differences in the era or timing when studies were conducted," he pointed out.
That’s not to say Merck and Pfizer saw no positive signs in the outcomes data. Researchers did spot a 30% reduction in the risk of hospitalization for heart failure, although that endpoint wasn’t part of the study’s hierarchical testing sequence.
“We’re obviously going to be looking at the data set from Vertis CV to understand more about this finding, and we look forward to sharing those analyses with the scientific community in the relatively near future,” Engel said.
In the meantime, Steglatro might be able to ride its rivals' coattails thanks to the perception of a so-called "class effect" around SGLT2s.
"The clinician will be looking at the similarities across the class on a variety of endpoints, and it'll be important to recognize that, while the point estimates for these various studies will differ, where there are similar patterns is what I think clinicians will probably base their conclusions on," Engel said.