Express Scripts Coverage, FDA Label Update Boost Rybelsus
Novo Novardisk's Rybelsus will now be covered by Express Scripts. IPD Analytics has been keeping up-to-date with 2020 formulary postings and it seems Novo is still in negotiations. There is some difference in opinion regarding how payers will set their formulary management strategy on GLP-1s.
Sharon Bender | www.aishealth.com
Access to Novo Nordisk’s Rybelsus (semaglutide)—the first oral glucagon-like peptide-1 receptor agonist (GLP-1) to treat adults with type 2 diabetes—got a major boost January 17th, 2020 when Novo said Express Scripts, part of Cigna Corp., will cover the agent. Rybelsus was approved in September 2019 and is available as a once-daily tablet version of the drugmaker’s Ozempic (semaglutide), a weekly injection launched in 2018. “We’ve been keeping a keen eye on the new 2020 formulary postings, watching weekly, and monitoring all the big payers’ formularies, and it’s been interesting to note that it looks as though Novo is still in negotiations” for Rybelsus, Jeffrey Casberg, M.S., R.Ph., Vice President of Clinical Pharmacy at IPD Analytics, told AIS Health. “You would think by now, more often than not you’d see more formularies updated, and we haven’t seen that yet.” IPD provides drug intelligence and consulting to stakeholders across the pharmaceutical landscape. Casberg represented the payer community on the Institute for Clinical and Economic Review’s (ICER) November policy roundtable panel in which clinical, manufacturer, payer, and patient advocate participants discussed key questions identified by ICER researchers related to oral semaglutide’s cost-effectiveness. A report of the panel’s recommendations, “Oral Semaglutide for Type 2 Diabetes: Final Policy Recommendations,” was published December 9, 2019 along with ICER’s “Oral Semaglutide for Type 2 Diabetes: Effectiveness and Value, Final Evidence Report.” ICER is an independent non-profit research organization. “Most payers evaluate any drug of any drug class based on safety, efficacy and cost,” he said. “Usually they’ll evaluate the product on safety and efficacy first. And then, based on that, the tiebreaker will be cost.” “The payers’ goal is to provide the best level of care at a reasonable cost,” he added. “Controlling that cost is of concern.” Initial therapy for type 2 diabetes usually begins with metformin, Casberg says. Commonly, other agents will need to be added on to help patients reach their A1c goal. HbA1c, or A1c, is a measure of average blood glucose control, reported as the percentage of hemoglobin that is glycated. Frequently used add-on products include DPP-4s (dipeptidyl peptidase-4 inhibitors) such as Januvia (sitagliptin, from Merck & Co., Inc.), and SGLT2s (sodium-glucose co-transporter 2 inhibitors) such as Jardiance (empagliflozin, from Boehringer Ingelheim/Eli Lilly and Co.) and Farxiga (dapagliflozin, from AstraZeneca plc). “Primary care providers (PCPs) tend to go with DPP-4s and SGLT2s because they’re orally administered. They don’t have to do a lot of teaching to the patient. They’re fairly well tolerated,” says Casberg. If a patient’s disease is more severe or they’re not getting to their A1c goal with those classes, at that point a PCP might refer a patient to an endocrinologist for treatment with insulin or GLP-1s, which are injected. “The endocrinology offices have nurse specialists and can spend more time with the patient. So, the GLP-1 products have primarily been used by specialists rather than PCPs,” he says. “Utilization has been self-limiting, you might say. [Payers] haven’t put too many restrictions around these products because utilization hasn’t blown up.” Andy Behm, Pharm.D., vice president of Express Scripts’ Office of Clinical Evaluation & Policy, told AIS Health before the PBM’s Rybelsus coverage decision was announced that his organization’s formulary development process includes distinct clinical and financial evaluations. “Only after a medication is considered generally clinically similar to other therapeutic options do we conduct a full financial evaluation to determine formulary status. While ICER is not formally part of our evaluation process, Express Scripts tracks their decisions and recommendations,” Behm said. Terms of the Rybelsus agreement between Express Scripts and Novo Nordisk haven’t been disclosed.
GLP-1s Are Highly Effective but Costly
Rybelsus lists for $9,264 annually before rebates and discounts; Ozempic’s price is $9,240, according to Novo Nordisk. This puts them in line with other GLP-1s. But, noted Casberg, “the DPP-4s and SGLT2s are significantly less expensive,” with annual list prices in the $6,000 range for Januvia and Jardiance. “When you get to the injectable GLP-1s, you’re talking a $10,000 list price, so there’s a significant price differential. You would think managed care would have put some type of management barriers in front of these GLP-1 products, but they haven’t,” he said. That’s because specialist-driven utilization of the injectables has created what he calls an “artificial barrier” to broader use. “The GLP-1s are looked at as high-efficacy products,” explained Casberg. “They reduce A1c by 1% to 1.5%, whereas products like the DPP-4s and SGLT2s at the high end can get up to 1% reduction. From a safety or side effect profile, I think the bigger concern is the side effect profile.” The GLP-1s do have nausea and vomiting or gastrointestinal side effects, he said, which are usually more pronounced in the first month or two of therapy. The other differentiating factor is weight loss, as people with type 2 diabetes tend to gain weight and GLP-1 products promote weight loss. “Having an oral option with these features is a big deal in the diabetes community today,” Casberg added. The introduction of oral Rybelsus potentially could significantly shift utilization to GLP-1s. Approximately 10% of the U.S. population has diabetes, Casberg said. “If everybody moved from a lower-cost oral product to a higher-cost oral product, it could really break the bank for these payers.” Ozempic, Novo Nordisk’s injectable semaglutide, achieved blockbuster status by earning $1 billion in sales during the first three quarters of 2019. Currently marketed single-agent GLP-1s include: ✦ Rybelsus (semaglutide, from Novo Nordisk), once-daily oral, approved 2019; ✦ Ozempic (semaglutide, from Novo Nordisk), weekly injection, approved 2017; ✦ Bydureon BCise (exenatide extended-release, from AstraZeneca), weekly injection, approved 2017; ✦ Adlyxin (lixisenatide, from Sanofi-Aventis), once daily injection, approved 2016; ✦ Trulicity (dulaglutide, from Eli Lilly), weekly injection, approved 2014; ✦ Bydureon (exenatide extended-release, from AstraZeneca), weekly injection, approved 2012; ✦ Victoza 2-Pak (liraglutide, from Novo Nordisk), once daily injection, approved 2010; and ✦ Byetta (exenatide, from AstraZeneca), twice-daily injection, approved 2005. The ability to reduce cardiovascular (CV) risk in patients with type 2 diabetes is another factor that could drive greater GLP-1 utilization. Said Express Scripts’ Behm: “Over the past few years, a number of type 2 diabetes medications have demonstrated that they not only reduce blood glucose levels, but they also may reduce long-term cardiovascular risk. As such, clinical guidelines are moving in a direction where these agents are suggested earlier in treatment. Oral Rybelsus provides another therapeutic alternative for patients who require type 2 diabetes management. While it has some favorable characteristics, it is still simply one of many options.” On January 16, 2020, Ozempic won won FDA approval of an additional indication to reduce the risk of major cardiovascular events in adults with type 2 diabetes and known heart disease. Novo Nordisk is seeking the same CV indication for Rybelsus, with the FDA’s decision expected soon. Meanwhile, also on January 16, Rybelsus’ prescribing information was updated to include CV data from a clinical study. The American Diabetes Association’s Standards of Medical Care in Diabetes—2020 recommend that use of SGLT2s and GLP-1s be considered in patients with or at high risk for cardiovascular disease, kidney disease, or heart failure regardless of patients’ current A1c or A1c target.
Payers Take Varying Approaches
ICER’s final policy recommendations to payers for oral semaglutide suggest that prior authorization (PA) criteria for antihyperglycemic products be based on clinical evidence, specialty society guidelines, and input from clinical experts and patient groups. The panel also said payers might consider requiring attestation from providers that a patient’s A1c level remained above target after an adequate trial of metformin. Clinicians on the panel disagreed, saying the requirement would create an administrative burden without added benefit since metformin is nearly universally used as first-line therapy.
Oral Delivery Could Be Game-Changer
“I think the initial recommendations about authorization criteria are pretty straightforward,” said Casberg, who sat on the policy panel. “Equally, if not more important, for payers in the development of criteria, is whether or not they will be managing oral semaglutide or leaving it alone.” Currently there is little payer management of type 2 diabetes treatments, the ICER panel heard. However, patient preference for oral therapies has limited early-line use of GLP-1s. The introduction of an oral GLP-1 could change that paradigm. Casberg sees three potential approaches payers could take to manage GLP-1s. The first would be to “leave management the way it is, not putting any hurdles or step therapies in front of oral semaglutide and letting providers decide what they’ll use.” That would open the door to more use of oral semaglutide by PCPs. Or, he says, payers could require a step through a preferred injectable GLP-1 to access Rybelsus. A more aggressive approach would be to require a routine step through SGLT2s or DPP-4s to access GLP-1s, which clinicians on the panel said lacked clinical nuance. Concurrent therapy with an SGLT and GLP-1 is common, they noted. Additionally, the panel recommended that payers not include an A1c criterion for PA renewal given oral semaglutide’s benefits beyond A1c control. It was further recommended that given type 2 diabetes prevalence and oral semaglutide’s safety profile, prescribing not be restricted to specialists.