Treatment for heart failure still relies significantly on tried-and-true generic drugs, but new brand-name entrants — including Novartis’ Entresto (sacubitril/valsartan) and Amgen’s Corlanor (ivabradine) — are important additions to prescribers’ clinical arsenals against the high-mortality condition, industry insiders say.
In fact, a newly approved expanded indication for Entresto, plus more products recently approved and in the pipeline, could shift the balance more toward brand-name drugs in heart failure treatment, the insiders say.
“Generic heart failure drugs, including beta blockers, ACE inhibitors, and ARBs [angiotension receptor blockers] have historically been used and continue to be the backbone of therapy,” says April Kunze, Pharm.D., senior director of clinical program development for Prime Therapeutics. “However, in the past few years, additional treatment options have become available. Entresto is now recommended as a first-line treatment option in patients with an ejection fraction <= 40%.”
Novartis said Feb. 16 that its heart failure drug Entresto won an expanded indication from the FDA to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. The label also states that LVEF is a variable measure and clinical judgment should be used in deciding which patients to treat, according to Novartis. The label expansion will enable physicians to offer Entresto to a wider range of patients, the company added.
Prime Therapeutics currently prefers Entresto on formulary, and the PBM “will evaluate if clinical guidelines update its place in therapy for HFpEF [heart failure with preserved ejection fraction] given the recent expanded approval,” Kunze says.
Currently, Prime recommends that plans remove prior authorizations for Entresto in order to encourage its use, Kunze says. According to a poster that the PBM presented at the Academy of Managed Care Pharmacy Nexus 2020 virtual event last October, Prime members adherent to Entresto therapy for a year had reduced medical visits and expenditures, with savings totaling $6.7 million when comparing patients’ treatment costs to their costs prior to starting Entresto. To perform the study, Prime analyzed integrated medical and pharmacy claims data for 658 commercially insured members, and found average savings of $10,177, or 22%, per patient.
“Entresto represents an advancement in heart failure therapy that is being recognized as the new standard of care,” says Mesfin Tegenu, CEO and chairman of RxParadigm, a pharmacy benefit cost management start-up focused on providing tools and transparency.
Entresto is recommended for use as an alternative to ACE inhibitor or ARB therapy and also can be used in combination with other heart failure medications, Tegenu tells AIS Health.
Tegenu says that Entresto, which has an average retail price of around $600 per month, typically is placed on formularies as a preferred brand drug. Meanwhile, Amgen’s Corlanor can be beneficial in reducing heart failure-associated hospitalization for patients with symptomatic (NYHA Class II-III) stable chronic heart failure with a left ventricular ejection fraction of less than or equal to 35% who are receiving a maximal tolerated targeted dose of a beta blocker and in sinus rhythm with a heart rate of 70 beats per minute or greater at rest, Tegenu says.
Prime prefers Corlanor on formulary, Kunze says, noting that treatment guidelines recommend it as an add-on to standard therapy in patients who continue to have an elevated heart rate despite treatment with a beta blocker.
“The target for Colanor is to slow down heart rate,” Tegenu explains, adding that Corlanor typically is placed on formularies as a preferred or non-preferred brand, and may be started when the patient is not being adequately controlled on optimally dosed beta blocker therapy. “Unlike the well-proven mortality benefits of beta-blocker therapy, Corlanor is not considered a substitution for beta-blocker therapy and should be considered for additional therapy following the maximal tolerated targeted dose of a beta-blocker.”
Entresto and Corlanor represent advances in treatment for chronic heart failure, Tegenu says. “Both therapies were poised to change the landscape of treatment for patients with heart failure, given their unique mechanisms of action,” he says.
“Entresto has been considered an advancement in therapy as represented in the clinical guidelines,” Kunze says. “Corlanor has failed to gain much market share given its prescribing limitations.”
In addition, there are more therapies on the horizon. Merck’s Verquvo (vericiguat), a soluble guanylate cyclase (sGC) stimulator, was approved by the FDA on Jan. 20 to reduce the risk of cardiovascular death and hospitalization following a hospitalization for heart failure or need for outpatient intravenous diuretics in adults with symptomatic chronic heart failure and ejection fraction less than 45%. Verquvo, which received a priority regulatory review from the FDA, is the first treatment approved for chronic heart failure specifically for this group of patients.
It’s still unclear how Verquvo will fit into heart failure treatment, Tegenu says: “With lack of current support by treatment guidelines standards, Verquvo’s value will need to be further evaluated.”
FDA Reviews Jardiance for Heart Failure
AstraZeneca’s sodium-glucose co-transporter 2 (SGCT2) drug Farxiga (dapaglifozin) was approved in May 2020 by the FDA to reduce the risk of cardiovascular death and hospitalization for heart failure in adults who have heart failure (NYHA Class II-IV) with reduced ejection fraction with and without type 2 diabetes. That builds on Farxiga’s earlier approvals to treat type 2 diabetes and patients with both heart failure and type 2 diabetes. Jardiance (empagliflozin) from Boehringer Ingelheim and Eli Lilly and Co. may become the second SGLT2 drug approved for chronic heart failure with reduced ejection fraction, with an expected FDA review in late 2021, Tegenu says. Jardiance currently holds FDA approval for use in diabetes.
Additional heart failure drugs are in late-phase clinical trials. Cytokinetics, Inc. is developing omecamtiv mecarbil, a novel, selective cardiac myosin activator for the potential treatment for heart failure with reduced ejection fraction.
In addition, Lexicon Pharmaceuticals, Inc., is preparing to apply for FDA approval for sotagliflozin, the first dual inhibitor of both SGLT1 and SGLT2. “Sotaglifozin is anticipated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent visits for heart failure in adult patients with type 2 diabetes with either worsening heart failure or additional risk factors for heart failure,” Tegenu says.
Plans Want to Prevent Readmissions
Health plans also are turning to targeted disease and care management programs to focus on preventing hospital readmission, reducing mortality and reducing costs in heart failure, Tegenu says. “Heart failure is a major health concern due to the high rates of morbidity and mortality despite optimal therapy,” he says. “The prevalence, especially in the elderly population, will continue to increase over the next decades as a result of the demographic trends. Concerns for hospitalization and high readmission rates continue to plague health plans.”
Targeted disease or care management programs should take a multidisciplinary approach with cardiologists, primary care physicians, nurses, pharmacists and other health care professionals, and primarily should target the high-risk symptomatic patients, Tegenu says. “Remote-monitoring congestive heart failure programs plus medication therapy management programs, where patients are closely tracked and followed post-discharge (e.g., weight, functional status, nutrition, symptom monitoring), along with patient education and interventions such as medication adherence and self-care follow-up care, are effective in the management of heart failure.”
Tegenu notes that the heart failure death rate remains very high despite new treatment options: “Avoiding hospitalization and preventing readmission remain the focus in the management of heart failure,” he says. “In addition, we have to manage diabetes well, since there is a strong linkage between these comorbid conditions. We have more treatment options now. If we can be more aggressive and adopt remote monitoring, medication optimization and adherence monitoring, I am optimistic that we will see improvement in the mortality rate.”
by Jane Anderson
Learn more about MMIT’s Analytics solution to understand market access and payer coverage.