1. What’s happening
As the launch gets moving for Lipfendra (enlicitide decanoate), Merck's recently approved pill for cholesterol-lowering in adults, questions remain about reimbursement and adoption dynamics.
- CEO Rob Davis cautioned that establishing access is going to take time: "We are expecting to see the pace not be as fast out of the gate," he said on an earnings call last week in response to an analyst question about the initial speed of access.
- Inherent in that admission is the realization that LDL-lowering is a biomarker, not an outcome.
- However, ordering has begun, and it should hit US pharmacy shelves (and the TrumpRx buying site) shortly, the company said on the call.
- Additional regulatory reviews are under way in the EU and China.
2. What’s the big deal
As the first-of-its-kind formulation of a PCSK9 inhibitor in a daily oral option, Lipfendra promises to extend the reach of this therapeutic approach to many more patients than the three already approved injectables have so far. The launch includes a direct-to-patient program and more affordable pricing.
- Relative to statins, injectable PCSK9s have fairly low use in the primary care setting, so Merck has said it also plans an educational effort among primary care physicians (PCPs) about the new therapy.
- Two influential medical groups—the American College of Cardiology (ACC) and American Heart Association (AHA)—have provided a launch tailwind by modifying LDL cholesterol goals in their guidelines to lower levels for people who are at very high risk of heart attack and stroke from atherosclerotic cardiovascular disease.
- Their guideline also recommends non-statin therapy, including PCSK9 inhibitors, if LDL is not adequately lowered by healthy lifestyle habits and statin therapy.
- Merck’s advantage is the 64.6% reduction in LDL cholesterol from baseline when added to background treatment with a statin and its better performance against other oral non-statin therapies in the phase 3 CORALreef AddOn study.
- Still, Merck's ability to democratize access depends on whether insurers grant coverage, and they may hold out until they see proof in the form of heart protection data, not due until 2029.
3. What’s at stake
There are 30 million people receiving lipid-lowering therapies who are not at their recommended LDL levels. More go untreated.
- Payers funnel most patients with high cholesterol to any of the generic statins, like atorvastatin, simvastatin, or rosuvastatin.
- The monoclonal antibody PCSK9s (the biweekly/monthly Amgen and Sanofi injections Repatha and Praluent, respectively, and Novartis' twice-yearly Leqvio) only reach about 5% or less of the total market, Davis noted.
- Merck has said it views Lipfendra more as a market-expansion play than a switch opportunity.
4. What’s it mean for commercial execs
While Lipfendra's more affordable pricing ($315 per month vs. $500 to $600+ per month for its next-nearest branded competitors) and the updated dyslipidemia treatment guidelines are carrots for payers to extend coverage, the lack of a cardiovascular outcomes trial (CVOT) on the label may keep some on the sidelines, noted Robert Rouse, Beghou Partner and head of our Value & Access unit.
- “With the same efficacy as the injectable PCSK9s at a lower cost, payers are likely to say, ‘Sure, I'll prefer Lipfendra over the biologics to save money,’” Rouse said. “But that limits the brand to just switching patients in a very small segment of the market. To go beyond that, in a world with generic Lipitor, Merck really needs to respond to the payer perceptions of, ‘Why do I need anything else?’”
- Merck will surely build the drug’s value proposition through RWE and HEOR data over the next year or two, leading to a “longer, slower ramp-up,” Rouse explained.
- Even when the CVOT reads out in 2029, it may be hard to change the launch trajectory, since most new drugs’ launch curves are defined in their first six months, one long-running study has shown.
- It will also take time for Merck’s sales and marketing teams, respectively, to translate the excitement seen in the scientific community to the primary care setting and to patients, Merck CFO Caroline Litchfield explained, also on the conference call.
5. What’s next
One analyst interpreted Davis' comments on the initial pace of access as Merck "walking down" Lipfendra sales, while other analysts predicted sales will be faster than the previously approved PCSK9 drugs.
- RBC Capital Markets analyst Trung Huynh estimates "negligible" sales this year, while Daina Graybosch of Leerink Partners forecasts product revenue of $476 million in 2027.
- "Long term, [we] continue to expect to see this to be definitely a blockbuster opportunity as we move forward," added Davis.