Inclisiran’s upside
On the other hand, inclisiran has a couple of important advantages. First, its mechanism of action means that effective treatment involves one injection every 6 months following a patient’s first two injections at onset and after 90 days, with all injections administered in a clinician’s office. In contrast, both of the monoclonal antibodies require injections every other week, a schedule that depends on patient self-injections using prefilled syringes obtained from a pharmacy.
Mitchel L. Zoler/MDedge News
Dr. Robert S. Rosenson
Twice-a-year dosing by a clinician can be a major attraction because it helps ensure treatment compliance, aids patients with physical or psychological limitations to self-injection, reduces the pill burden for patients who require multiple medications, and facilitates frequent travelers who would otherwise need to carry syringes with them on trips, Dr. Rosenson noted.
The second big advantage of office-based administration of inclisiran for U.S. Medicare patients is that the treatment is billed under a patient’s part B coverage, usually resulting in easier coverage and a significantly lower patient co-pay, compared with Medicare’s coverage for a pharmacy-dispensed agent, which is covered under Medicare part D. “Part B coverage is financially more doable” for most Medicare patients, said Dr. Rosenson.
The administration schedule for inclisiran as well as its superior Medicare coverage makes the agent “transformative” for LDL-C lowering in patients for whom treatment delivery, frequency, and payment are issues, he said.
Inclisiran uptake modest after FDA approval
Despite these pluses, uptake of inclisiran has been modest since it received U.S. marketing approval in December 2021. In its most recent quarterly financial filing, in October 2022, Novartis reported total worldwide income from inclisiran (Leqvio) of $70 million during the first 9 months of 2022, although a Novartis spokesperson noted that the company has seen “positive trends in uptake” over the course of 2022. Inclisiran is labeled as an “adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require additional lowering” of LDL-C.
During 2022, inclisiran uptake lagged because of the usual problems that slow the introduction of new drugs and new drug classes, especially ones that require dosing by a clinician. Months were spent waiting for billing codes to roll out, for clinical staffs to incorporate inclisiran injections into their routines, and for commercial insurers to get up to speed on their coverage, Dr. Rosenson said.
Also, a key step for widespread uptake of a new medication for improving cardiovascular disease outcomes – results from phase 3 studies that document safety and efficacy for these outcomes – remains several years off. The ORION-4 trial and the VICTORION-2P trial, each assessing the impact of inclisiran on cardiovascular disease events in roughly 15,000 people, will need about another 3-4 years before their results become available.
Professional medical societies that issue cardiovascular-disease management guidelines “prefer agents with proven benefits in phase 3 trials,” Dr. Rosenson noted.
Hence, the most recent update to U.S. LDL-C–management guidelines, released in the second half of 2022 by the American College of Cardiology as an Expert Consensus Decision Pathway, said this about the current role for inclisiran: “At the present time, a PCSK9 monoclonal antibody is preferred as the initial PCSK9 inhibitor of choice in view of its demonstrated safety, efficacy, and benefits for cardiovascular outcomes in the FOURIER [for evolocumab] and ODYSSEY Outcomes [for alirocumab] trials. The ORION-4 and VICTORION-2P cardiovascular outcomes trials with inclisiran are currently underway, and their completion is anticipated in 2026 and 2027, respectively. In view of the twice-yearly dosing regimen, inclisiran may be considered in patients with demonstrated poor adherence to PCSK9 monoclonal antibodies. Patients with adverse effects from both PSCK9 monoclonal antibodies or those who may be unable to self-inject may also be considered for therapy with inclisiran.”