Major Drugs Nearing FDA Approval in Late 2024
by Emily Crisano, PharmD and Jason Peterson, R.Ph
As 2024 winds down, the Food and Drug Administration (FDA) is considering the approval of several promising drugs. Among the contenders are three highly anticipated drugs—Lebrikizumab, Garadacimab and Marstacimab—with the potential to significantly improve patient outcomes, reduce the need for medical intervention and provide more convenience compared to their competition.
Their approval could impact both patient outcomes and healthcare costs, making it crucial for payers to carefully evaluate their potential benefits and implications.
These drugs represent advances in their respective fields, targeting complex and often debilitating conditions with innovative mechanisms of action. For payers, the introduction of these therapies necessitates a closer examination of clinical efficacy, cost-effectiveness, and the potential for long-term savings. As these drugs vie for market share against established treatments, their pricing strategies and the convenience they offer patients will be key factors in their adoption and formulary placement.
Keep reading as we explore these drugs, their mechanisms, clinical trial results and the potential impact on both patients and payers.
Lebrikizumab
Lebrikizumab is under FDA review for moderate to severe atopic dermatitis (AD), more commonly known as eczema.
This condition causes dry, itchy and inflamed skin and affects approximately 16.5 million adults (7.3%) in the U.S., with about 40% of those in the moderate to severe category. In addition, about 9.6 million U.S. children under the age of 18 have AD, with one-third of those having moderate to severe disease. Patients with moderate to severe symptoms may experience thickened skin, oozing, crusting and raw sensitive skin from scratching. AD may lead to other long term health issues including skin infections, asthma and allergies, eye problems, sleep issues, heart concerns and mental health challenges.
Lebrikizumab is classified as an interleukin-13 (IL-13) inhibitor and shares this mechanism of action with Adbry (tralokinumab), which is already on the market for use in adults and children 12 years and older with moderate to severe AD. Lebrikizumab is seeking approval for this same indication in the same patient population and would compete with IL-4 inhibitor, Dupixent (dupilumab).
The clinical trial data for lebrikizumab consists of three phase-III trials in which two tested against placebo (ADvocate1, ADvocate2) and the third (ADhere) evaluated lebrikizumab in combination with topical corticosteroids versus topical corticosteroids alone. In the ADvocate1 and ADvocate2 trials, 43% and 33% of patients receiving lebrikizumab achieved an Investigator’s Global Assessment (IGA) of clear/almost clear skin at week 16 compared to 13% and 11% in the placebo groups, respectively. In the ADhere trial 41% of patients receiving lebrikizumab in combination with topical corticosteroids achieved IGA of clear/almost clear skin at week 16 compared to 22% in the topical corticosteroids alone group.
If approved, lebrikizumab will be available as a subcutaneous injection that can be self-administered every 2 weeks. Lebrikizumab is expected to launch at an estimated price of $50,000 per year which is similar to Adbry and Dupixent. The efficacy of lebrikizumab is comparable to market leader Dupixent based on cross-trial analysis, but that may not be enough to drive market penetration unless Eli Lilly provides greater discounts to payers than what is offered by its competitors.
Garadacimab
Garadacimab is a novel, first-in-class, recombinant monoclonal antibody that targets activated factor XII (FXII).
FXIIa is a plasma protein that initiates the kallikrein-kinin cascade of hereditary angioedema (HAE) attacks. HAE is a very rare and potentially life-threatening condition that involves recurrent attacks of severe swelling (angioedema) in various parts of the body, including the hands, feet, genitals, stomach, face and/or throat. Swelling that occurs in the airway can possibly restrict breathing and be fatal. HAE attacks or episodes may be triggered by physical trauma or emotional stress but can sometimes occur without a trigger. The estimated global prevalence of HAE in the general population is one individual per 50,000 and it is estimated that only 6,000 people in the United States live with HAE.
The pivotal Phase-III trial (VANGUARD) evaluated monthly subcutaneous administration in the prevention of HAE attacks compared to the placebo for 6 months in 65 patients with type I or II HAE at least 12 years of age. The results showed the mean investigator-confirmed hereditary angioedema attacks per month were significantly reduced by 87% when compared to placebo.
What makes this product unique compared to the other agents currently approved to treat HAE is that by targeting FXIIa, garadacimab inhibits the kallikrein-kinin cascade at the top compared to other HAE therapies that target downstream mediators. The FDA has granted garadacimab Orphan Drug designation for the treatment of HAE.
If approved, patients will have the benefit of an auto injector (pre-filled pen) for convenient administration. Unfortunately, the annual cost will be close to the upper end of the range for these products at nearly $750,000 due to the convenience the once-monthly self-administration offers. Payers will need to consider the added convenience and potential for better adherence to therapy as an offset to higher medical costs when determining formulary placement of garadacimab.
Marstacimab
Marstacimab is in development as a prophylactic treatment to prevent or reduce the frequency of bleeding episodes in patients with severe Hemophilia A and moderately severe to severe Hemophilia B with and without inhibitors.
Hemophilia includes a family of rare genetic blood disorders due to a clotting factor deficiency: FVIII in hemophilia A and FIX in hemophilia B. Hemophilia currently impacts over 400,000 people across the globe and is typically diagnosed early in life.
Marstacimab is a human monoclonal immunoglobulin G isotype, subclass 1. It targets the tissue factor pathway inhibitor (TFPI), a natural anticoagulation protein that functions to prevent the formation of blood clots. This agent has shown the potential to address the diverse needs of appropriate patients with hemophilia A or B without inhibitors with weekly subcutaneous administration in a flat dose that is not weight-based, and with low monitoring requirements.
Results from the phase-III open-label trial (BASIS) that enrolled patients aged 12 to 74 years showed subcutaneously administered marstacimab dosed weekly reduced bleeds by 92% in patients with severe hemophilia A and moderately severe to severe hemophilia B without inhibitors to factor VIII (FVIII) or factor IX (FIX). According to Pfizer, results for patients with inhibitors should be available in late 2024. In addition, a phase-III trial (BASIS KIDS) is also ongoing to investigate the safety and efficacy of marstacimab in children 1 to less than 18 years of age with severe hemophilia A or moderately severe to severe hemophilia B with or without inhibitors.
Marstacimab’s application for approval was submitted to the FDA late last year for individuals living with hemophilia A or B without inhibitors. Once approved, marstacimab would be an alternative treatment to intravenously dosed factor treatments for hemophilia A (FVIII) and B (FIX) and Hemlibra (emicizumab) for hemophilia A.
Most likely, marstacimab will be priced very similarly to those agents in the $500,000–$750,000 per year range. The convenience of once weekly flat dosing will simplify treatment for many patients and payers will need to consider the overall treatment costs and potential for improved adherence and outcomes with marstacimab when compared to competitive treatments.
Moving Forward
As 2024 draws to a close, these highlighted treatments are expected to usher in positive changes for patient care. While they will compete with established therapies, their convenience and potential for improved outcomes may influence market adoption.
Payers will need to carefully consider clinical benefits, net costs and long-term savings when determining formulary placement. Some of these products may enter the market on the higher end of pricing compared to their competitors, but the upfront investment may result in overall medical savings in the long term.
References
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