Recent FDA-approved drugs of interest to underwriters

Rezdiffra (resmetirom, approved March 2024) is a first-of-its-kind, once-daily oral treatment indicated for metabolic dysfunction-associated steatohepatitis (MASH), a condition previously referred to as nonalcoholic steatohepatitis (NASH) that affects an estimated 1.5%–6.5% of U.S. adults.*

MASH is a form of fatty liver disease characterized by inflammation and cell death that can lead to fibrosis and cirrhosis. Rezdiffra is the first FDA-approved treatment for this condition and works by reducing liver fat accumulation through partial activation of thyroid hormone receptors in the liver and should be used in conjunction with diet, exercise, and/or therapies, including vitamin E and those focusing on weight loss. While additional trials are ongoing to verify Rezdiffra’s clinical benefit, existing trials have shown significantly more patients taking Rezdiffra achieved MASH resolution or an improvement in liver fibrosis compared to those on a placebo.

Underwriters should expect to see Rezdiffra via Irix Prescription Data in those with a diagnosis of MASH with moderate to advanced liver fibrosis. Because of its high cost and the potential need for a liver biopsy before beginning therapy, the initial use of this medication is expected to be low relative to the percentage of Americans with MASH/NASH. Therefore, underwriters should continue to look for diagnoses found through medical claims or records, as well as other treatments addressing risk factors for MASH such as those promoting weight loss and blood sugar control.

Anticipated relative mortality: High (>220%).

*Definition & Facts of NAFLD & NASH | NIDDK. National Institute of Diabetes and Digestive and Kidney Diseases. 

Vafseo (vadadustat, approved March 2024) is a once-daily oral treatment for anemia due to chronic kidney disease (CKD) in those who have been receiving dialysis for at least three months. This is the second oral option for anemia from CKD in those on dialysis, following the approval of Jesduvroq (daprodustat) in February of 2023. Both agents work to prevent the breakdown of hypoxia-inducible factor (HIF), which leads to enhanced production of red blood cells. These products have similar efficacy and safety profiles as erythropoiesis-stimulating agents (ESAs, such as Epogen/ epoetin alfa) in those on dialysis.

Underwriters should expect to see Vafseo via Irix Prescription Data as an alternative to ESAs in those experiencing anemia due to CKD while on dialysis. Medical Data claims associated with CKD and dialysis treatment are expected to accompany fills of Vafseo, while clear indicators of CKD on prescription profiles may be absent. Despite being approved earlier in 2024, this product likely won’t become available until early 2025.

Anticipated relative mortality: High (>500%).

Tryvio (aprocitentan, approved March 2024) is a once-daily oral treatment indicated for hypertension not controlled by other agents. By blocking the effects of endothelin on vascular smooth muscle, Tryvio helps to relax blood vessels (which lowers blood pressure) and can help decrease production of aldosterone, one of the hormones implicated in the causation of elevated blood pressure. This represents the first unique therapeutic pathway for an anti-hypertensive in nearly 40 years. Clinical trials found Tryvio helped to further reduce blood pressure in individuals with elevated readings despite being on at least three anti-hypertensive agents.

Underwriters should expect to see Tryvio via Irix Prescription Data as an add-on therapy in those with difficult-to-control hypertension, as inexpensive, first-line medications will likely be clinically preferred over a more expensive, brand name product. The medication is only approved for those already on multiple anti-hypertensives, although this may change over time as the manufacturer has indicated interest in researching its use in other conditions. Traditional therapies, such as ACE inhibitors (e.g., lisinopril), ARBs (e.g., losartan), thiazide diuretics (e.g., hydrochlorothiazide), and calcium channel blockers (e.g., amlodipine), continue to be preferred therapies for hypertension.

Anticipated relative mortality: Medium (180-220%).

Zepbound (tirzepatide, approved November 2023) is a subcutaneous injection given weekly for chronic weight management in patients who are obese, i.e., have a body mass index (BMI) of 30 or higher. Zepbound is also indicated for patients who are overweight, i.e., have a BMI of 27 or higher and have at least one weight-related comorbid condition (e.g., hypertension, dyslipidemia, type 2 diabetes, obstructive sleep apnea, cardiovascular disease).

Zepbound joins the ranks of other GLP-1 receptor agonists approved for chronic weight management, including Saxenda (liraglutide, approved December 2014) and Wegovy (semaglutide, approved June 2021), but differentiates itself by also working as an agonist on GIP receptors. Action on both GLP-1 and GIP receptors produces a synergistic effect, resulting in enhanced regulation of appetite and caloric intake. Of note, the active ingredient in Zepbound, tirzepatide, can also be found in Mounjaro (approved November 2022), which is used in the treatment of type 2 diabetes.

Underwriters should expect to see this medication via prescription fills for use in those who are obese, overweight, or trying to maintain their weight. Research has shown those who meet their weight goals but stop Zepbound are more likely to regain the weight they lost, which may lead to patients staying on this medication long term. Other factors should be considered when underwriting these cases, such as the presence of weight-related comorbid conditions referenced above.

Anticipated relative mortality: Low (<180%).

Opvee (nalmefene, approved May 2023) is a single-dose nasal spray given for emergency treatment of known or suspected opioid overdose. Opvee is an opioid antagonist and is used similarly to others within this class (e.g., naloxone/Narcan). This new product improves ease of administration and, when compared to naloxone, provides a longer duration of action, giving patients and providers another option to combat overdoses. At this time, Opvee is only available via a prescription while naloxone is approved for over-the-counter purchase by the FDA.

Underwriters should expect to see this medication via prescription fills. It is important to note that fills of Opvee may be found on the profile of a ‘Good Samaritan’ and not always the intended recipient of the medication, as some state laws allow all opioid antagonists to be obtained by concerned family or friends. We encourage consulting with your legal team on how to best underwrite opioid antagonist medications as many states have restrictions on the ways information about these drugs can used in insurance underwriting.

Anticipated relative mortality: High (>220%).

Lantidra (donislecel-jujn, approved June 2023) is a novel cell treatment indicated for adults with type 1 diabetes who cannot effectively control their A1c due to repeated episodes of severe hypoglycemia.

Type 1 diabetes is a chronic autoimmune disease caused by destruction of pancreatic islet cells, requiring lifelong insulin administration. One common side effect of insulin is hypoglycemia, which can be dangerous and cause unresponsiveness or seizures in severe cases. Lantidra is made from donor pancreatic islet cells and given in a healthcare setting as a single infusion into the hepatic portal vein. A second or even third infusion may be given depending on a patient’s response, with the goal of stopping the need for insulin injections altogether.

Underwriters may see administration of Lantidra via medical claims data in type 1 diabetics with repeated episodes of hypoglycemia. Of note, because Lantidra consists of donor cells, immunosuppressants (e.g., tacrolimus, sirolimus) are required with administration and continued long term to prevent rejection of the treatment. Because of this, Lantidra is anticipated to be a last-line therapy for difficult-to-control type 1 diabetes.

Anticipated relative mortality: High (>220%). Given this medication is used for uncontrolled or difficult-to-control type 1 diabetes, the anticipated mortality for those given this therapy is expected to be on the high end of the spectrum for type 1 diabetes.

Zurzuvae (zuranolone, approved August 2023) is a once-daily oral treatment given for one 14-day course for postpartum depression, the first oral agent approved by the FDA for this condition. While its mechanism is not fully understood, it is thought zuranolone functions similarly to the previously approved intravenous therapy for postpartum depression, Zulresso (brexanolone), by increasing the binding of GABA-A receptors in the brain to reduce symptoms of depression. Subjects in clinical trials saw improvement in symptoms in as little as three days, which is much quicker than most antidepressants on the market that work on different receptors in the brain.

Postpartum depression can be diagnosed during pregnancy, but it is more frequently diagnosed after delivery. Underwriters may expect to see fills of the medication on the applicant’s profile following delivery, but there should only be one 14-day course of the medication. Furthermore, other antidepressants (e.g., sertraline) may be prescribed in conjunction with or prior to the administration of zuranolone.

As an oral agent, Zurzuvae fills will show up in Prescription Data. Anticipated relative mortality: Low (< 100%)

Underwriters may expect to see this medication prescribed after a recent hospitalization or an emergency department visit for the treatment of acute heart failure, or in those with the risk factors indicated above. Sotagliflozin will usually appear on an applicant’s profile after other medications that are used to treat heart failure and / or diabetes, such as beta blockers (e.g., carvedilol, metoprolol), hypertension medications (e.g., lisinopril, losartan), diuretics (e.g., furosemide, spironolactone), diabetes medications (e.g., metformin, semaglutide), etc. Finding sotagliflozin on the profile likely signals worsening of disease or, at a minimum, concern for cardiovascular problems in those with these significant risk factors.

While sotagliflozin is approved for the treatment of type 1 diabetes in some parts of Europe, safety concerns have prevented its approval by the FDA for that condition in the United States at this time.

Because it’s an oral agent, underwriters will spot Inpefa fills in Prescription Data. Anticipated relative mortality: High (>220%)

Leqembi (lecanemab-irmb, approved January 2023) is an intravenous infusion given every two weeks for the treatment of early Alzheimer’s disease. Similar to Aduhelm (aducanumab-avwa, approved June 2021), lecanemab works by reducing the build-up of beta-amyloid plaques in the brain, one of the primary causes of Alzheimer’s disease responsible for impairing the brain cell’s functionality. In clinical trials, lecanemab was shown to only modestly slow both cognitive decline and loss of ADL (activities of daily living) function when compared to placebo. While it may slow or delay symptoms, it does not cure or reverse Alzheimer’s disease and is not approved for those with severe disease.

Underwriters may expect to see this medication used in those with early forms of Alzheimer’s disease; however, based on the population who participated in clinical trials, eligibility to use the product may be limited. Additionally, its biweekly administration in a clinic or hospital as well as its high list price of around $26,000 per year may further limit its use when cheaper, more convenient options (e.g., donepezil, memantine) are already available on the market.

As an intravenous infusion, Leqembi will found in Medical Data. Anticipated relative mortality: Medium (180-220%)