After a surprising FDA rejection and a change in manufacturing facility, Novartis has won FDA backing for its blockbuster hopeful Leqvio. With an additional year of preparation and a unique marketing strategy, the Swiss pharma believes it’s in better shape to launch the heart drug while steering clear of the problems that plagued other PCSK9 meds.
The FDA has greenlighted Leqvio, also known as inclisiran, as an adjunct treatment to diet and statin to lower the level of bad cholesterol in patients who have failed to control elevated low-density lipoprotein cholesterol (LDL-C) with statins. The go-ahead comes a year after an EU approval and a manufacturing inspection-related complete response letter from the FDA.
Novartis expects more than $2 billion peak sales for Leqvio, a PCSK9-targeted RNA interference therapy that was the centerpiece of the pharma’s $9.7 billion acquisition of The Medicines Company in early 2020. Leqvio’s product profile, paired with a carefully designed sales plan, means it’s better positioned to be successful compared with two earlier PCSK9 antibody drugs, namely Amgen’s Repatha and Sanofi and Regeneron’s Praluent, said Victor Bulto, Novartis’ head of U.S. pharmaceuticals business.
Fewer reimbursement obstacles
PCSK9 inhibitors have shown great efficacy in lowering LDL-C. In Leqvio’s case, the drug reduced bad cholesterol by around 50% over placebo in two phase 3 trials. Still, despite high market expectations, pushback from pharmacy benefit managers blunted the rollouts for Praluent and Repatha.
Leqvio’s situation is different, Bulto explained. While Praluent and Repatha are injections that patients can give themselves at home, Leqvio is administered by a healthcare professional. That means Leqvio’s reimbursement will be routed through the medical benefit pathway, where drug utilization isn’t as restrictive as the pharmacy benefit side, Bulto said.
Thanks to that setup, about two-thirds of patients eligible for Leqvio will have zero copays at launch, Bulto said. These include people who have Medigap insurance or those who dual-eligible for Medicare and Medicaid. Further, Novartis will offer zero copays for the commercial population, leaving only those on Medicare Advantage plans without the out-of-pocket benefit.
Make no mistake, Novartis still expects some level of restrictions from commercial payers, Bulto said, just “not to the degree that we would see in a pharmacy benefit launch.”
During Repatha’s and Praluent’s launches, the lack of data showing they could reduce heart-related events was one obstacle to obtaining favorable coverage. Leqvio’s own cardiovascular outcomes trial, dubbed ORION-4, likely won’t read out until 2026. Bulto thinks the outcomes discussion probably won’t have a fundamental impact on Leqvio’s launch.
A novel approach to marketing
For Leqvio’s U.K. launch, Novartis has partnered with Britain’s NHS to identify people at risk of heart disease and for whom statins don’t work. For the U.S. rollout, the Swiss pharma is deploying a similar population-level health approach.
In the past year or so, Novartis has been busy talking to the top 200 U.S. healthcare systems to establish a workflow to identify at-risk patients, stratify them and get them the right treatment. These systems treat 65% of patients with atherosclerotic cardiovascular disease (ASCVD), the target population of Leqvio, Bulto said.
“We want to go beyond the traditional model where we just deploy sales reps that educate physicians one after the other to try to make individual decisions better for patients,” Bulto said.
One of the key challenges ahead for Leqvio is that cardiologists aren’t familiar with the buy-and-bill payment model for physician-administered drugs. That’s where the collab with healthcare systems could help by putting in place reimbursement pathways.
As for those doctors not in the large systems, Novartis has established a network of alternative injection centers that could administer Leqvio for the doctors, with about 1,100 sites ready to go at launch.
Novartis has put a lot of emphasis on reimbursement and access to Leqvio’s launch given lessons learned from Repatha and Praluent. While it’s detailing Leqvio with the sales and marketing team behind the company’s blockbuster heart failure drug Entresto, it has hired a completely new reimbursement team that Bulto said is “the largest … in the industry.”
Poor patient compliance is another reason behind the lackluster uptake of the two older PCSK9 drugs. While Repatha and Praluent can be administered up to every month after the initial loading doses, Leqvio’s longer treatment interval of every six months also gives it an edge, Novartis figures.
“What we’re talking about is a chronic but asymptomatic disease … that you have to treat for life," Bulto said. "It doesn’t give you immediate symptoms, so the willingness to make an effort on an ongoing basis is much lower and the willingness to add a copay is also lower."
Once every six months happens to be the same frequency ASCVD patients see their docs, so they can get Leqvio during the visits, Bulto said.