The Medicines Co. (NASDAQ: MDCO) announced last week that its cholesterol-lowering medicine inclisiran, meant to be taken just twice a year, had passed a key test but offered no details. Some of those details arrived this morning.
At a medical meeting in Paris, a presentation from the test, a 1,617-patient Phase 3 study called ORION-11, did nothing to derail the expectation that inclisiran is just as safe and effective as other next-generation cholesterol fighting drugs.
However, as Xconomy reported, the data also don’t portend whether inclisiran, if approved by the FDA, will succeed commercially where two other, similar medicines—all of which reduce or block a cholesterol-boosting protein called PCSK9—have struggled.
“We believe inclisiran can change the treatment of cardiovascular disease,” MedCo CEO Mark Timney told Xconomy in an interview to discuss the data before Monday’s presentation.
Those are strong words. The two approved PCSK9 inhibitors—evolocumab (Repatha), from Amgen (NASDAQ: AMGN), and alirocumab (Praluent), from Regeneron Pharmaceuticals (NASDAQ: REGN) and Sanofi (NYSE: SNY)—were also supposed to change medical practice, particularly for people who can’t reduce potentially dangerous cholesterol levels with other medicines.
But insurers balked at their high prices and have curtailed use of Repatha and Praluent. Despite price concessions, evidence of longterm health benefits, and more, the two drugs have yet to generate $1 billion in annual sales combined, well short of once-lofty sales projections.
Inclisiran’s convenience could be the difference. It is injected twice a year, compared with the other two drugs that are self-injected one or twice a month.
Inclisiran could be “very beneficial, as long as it’s affordable and accessible,” said Prashant Vaishnava, a cardiologist at the Mt. Sinai Hospital in New York, with no ties to MedCo or other PCSK9 companies. But “if accessibility were to be a barrier, the advantage of twice-yearly administration would diminish.”
With the data presented today in Paris, MedCo hopes to convince doctors that inclisiran is just as safe and good at clearing LDL cholesterol as Repatha and Praluent.
Patients in the study began with average of 106 mg of LDL cholesterol per deciliter of blood, despite treatment with statins, the standard of care for treating high cholesterol. They got a shot of inclisiran at the start of the study, three months later, and then every six months afterwards, for a total of 18 months.
Their LDL cholesterol levels dropped 49 percent (58 mg/dl), which was 54 percent better than the patients taking placebo over the course of the study. Their average LDL-C levels were a time-averaged 50 percent lower than placebo patients from 90 to 540 days after getting their first shot as well. These were the study’s two main goals, and the results put inclisiran in the same ballpark as Repatha and Praluent. Cutting LDL cholesterol in half, starting from a baseline of 106 mg/dl is “impressive,” said Vaishnava.
Details about safety, which MedCo hinted last week would be impressive, showed that inclisiran patients in fact had slightly lower side-effect rates than the placebo patients (22.3 percent for inclisiran, 22.5 percent for placebo). Liver enzyme spikes, an indicator of possible liver damage, and plasma creatinine, a measure of kidney function, were even or favored inclisiran.
The biggest hiccup: More inclisiran patients (4.7 percent, vs. 0.5 percent placebo) had injection-site reactions. MedCo chief development officer Peter Wijngaard told Xconomy that the reactions were mostly mild and all “resolved spontaneously.”
Vaishnava was “concerned that nearly one in four patients in both [study] arms experienced an adverse event,” and wanted to see more granular details, which will come when the results are published in a peer-reviewed journal. Wijngaard countered that the side-effect rate is “fairly typical” of the patient group it studied.
Health outcomes also favored inclisiran over placebo. More placebo patients died (1.9 percent vs. 1.7 percent) or suffered malignancies (2.5 percent vs. 2.0 percent), heart attacks (2.7 percent vs. 1.2 percent) or strokes (1.0 percent vs. 0.2 percent) than those on inclisiran. But ORION-11 was not designed to study such weighty goals. They’ll have to be confirmed in MedCo’s 15,000-patient outcomes study, ORION-4, with final results expected in 2024.
The ORION-11 data “reinforces inclisiran as a potential front runner in the PCSK9 space,” wrote SVB Leerink analyst Joseph Schwartz. MedCo shares climbed 18 percent in pre-market trading Tuesday morning.
In the meantime, MedCo awaits results from two more Phase 3 studies, ORION-10 and 9, later this quarter. It could file for approval of inclisiran afterwards, assuming a successful outcome.
That’s when conversations with payers will heat up. CEO Timney said talks have already begun, and the company is considering “value-based agreements” that could tie inclisiran’s price to its performance. Regeneron and Amgen have cut creative deals with payers, too. Prescriptions have ticked up, but the deals haven’t significantly moved the needle.
Timney is well aware of those struggles. “We’ve learned a lot” from watching the PCSK9 story play out, he said. “And we’ve got a fundamentally different approach.”
He said the “cost of goods” for inclisiran is different than Repatha and Praluent. Inclisiran will be a high-volume, lower-cost product to make, Timney said, so MedCo could “reduce the price relatively quickly” as more patients get access. What’s more, he said, patients at risk of a heart attack or stroke may already be seeing a doctor every six months, which could make insurers more willing to ante up for a treatment that’s timed for those regular visits.
“You could coordinate those injections with two six-month visits,” Vaishnava says. “That lends itself to creative solutions that allow for adherence.”
Of course, it all comes down to the price tag. Before Praluent and Repatha launched in 2014, pharmacy benefit managers, who represent insurers in price negotiations, warned that a price tag of $10,000 a year would be unsustainable.
Despite that shot across the bow, Amgen and Regeneron priced their drugs north of $14,000 a year.
In the next year or so, we should learn how fundamentally different MedCo’s approach really is.