April 2025 Clinical Recap
Jake Goll, PharmD (jake.goll@theprismhealthgroup.com) serves as the clinical consultant at Prism Health Group, where he provides end-to-end oversight of clinical strategy through in-depth data analysis, proactive consultation, and subject matter expertise. Gene Therapy: Big Talk, Slow Uptake
Gene Therapy: Big Talk, Slow Uptake
Gene therapy has been a hot clinical topic, particularly within the past couple years, as these products offer a possible cure or long-term relief for rare diseases like muscular dystrophy, hemophilia, and sickle cell. When these products first started coming to market, a frequent question from plan sponsors outside of “how will we manage these drugs” was “what is our likelihood of incurring one of these claims?”
As we enter Q2 of 2025, I feel as though we’re in a similar place as we were a few years back when we started having more frequent conversations about gene therapy: still waiting for an influx of (or at least one or two) claims for plans – particularly larger ones.
Despite the attention, real-world utilization remains low. In 2024, all FDA-approved gene therapies generated roughly $2.2 billion in total sales, implying fewer than 1,000 patients received treatment at an average cost of $2.3 million per dose. Hemlibra, a non-gene therapy for Hemophilia A, saw $3.6 billion in sales with an estimated 6,800 patients treated. In contrast, Roctavian, the only approved gene therapy for Hemophilia A, saw just $28 million in 2024 sales – likely used in only 10 patients.
So far in 2025, Pfizer has halted production of its Hemophilia B gene therapy (Beqvez) due to zero sales. Additionally, Bluebird Bio, a gene therapy manufacturer once worth nearly $10 billion, was sold to private equity for $30 million.
What could be slowing uptake?
- Complex coverage pathways requiring both drug approval and hospitalization for administration.
- High costs averaging $2.3M per patient.
- Limited long-term data with most products approved in the last 3 years.
- Existing alternatives like Hemlibra for Hemophilia A offer effective, lower-burden options. Unlike other disease states with few treatment options or high mortality (e.g., spinal muscular atrophy), the hemophilia space already has strong treatment options that patients and prescribers are comfortable with, making demand for gene therapy more unenthusiastic, at least for now.
While gene therapy is highly effective and considered breakthrough therapy, not 100% of patients respond. Many manufacturers acknowledge this publicly on their websites. Most gene therapy drugs were FDA approved within the past 3 years and lack long-term efficacy (and safety) data.
New Twists with GLP-1 Compounding
Those keeping up with the GLP-1 buzz likely recall that the FDA declared tirzepatide and semaglutide to no longer be in shortage earlier this year, thus prohibiting the continued compounding of tirzepatide as of March 19th and semaglutide starting May 22nd. Under federal law, once a commercially available drug is no longer in shortage, compounding of that product is no longer permitted, except in very limited circumstances. Despite this, compounded GLP-1s remain widely advertised, particularly by telehealth vendors offering monthly or annual weight loss programs.
In response, Eli Lilly filed lawsuits last week against four telehealth companies: Mochi Health, Fellow Health, Willow Health, and Henry Meds, for illegally compounding and distributing tirzepatide products. Patients and plan sponsors should be aware of these key details:
- Among several allegations, Lilly is pursuing legal action against these companies for their questionable tactics, including compounding of an oral version of tirzepatide (Lilly’s FDA-approved products, Mounjaro and Zepbound, are injectables). Some companies are also adding ingredients like vitamin B12 to their formulations. They claim these changes qualify under a legal exception that allows compounding when a drug is in shortage or when the compounded version provides a significant clinical difference, such as a different dosage form or removal of an allergenic ingredient. By customizing formulations for individual patients, these telehealth vendors argue that their compounded products meet the exception criteria. However, these products have not been reviewed or approved by the FDA. Importantly, no FDA-approved oral version of tirzepatide exists, making these compounded alternatives particularly risky.
- Some telehealth vendors are still advertising compounded injectable semaglutide, even though compounding will be prohibited starting May 22nd. Several of these programs offer 12-month “deals” without clearly disclosing that they won’t be able to compound the drug past that date. While the use of compounded GLP-1s is generally not recommended, members considering these programs should understand that they’ll only receive a limited supply of semaglutide, something worth considering before committing to long-term plans.
Biosimilars in Focus: Soliris
Soliris (eculizumab), a biologic approved in 2007, is used to treat rare, complement-mediated disorders including paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), generalized myasthenia gravis (gMG), and neuromyelitis optica spectrum disorder (NMOSD). Though less prominent utilization-wise compared to Humira or Stelara in the biosimilar landscape, Soliris carries a significant cost, up to $678,000 annually per patient.
As a provider-administered drug, Soliris typically falls under the medical benefit. Plan sponsors should be aware of a meaningful cost-saving opportunity with the recent launch of two biosimilars:
- Bkemv (Amgen) – launched March 1, 2025 at a 9% discount to Soliris’ WAC
- Epsyqli (Samsung Bioepis/Teva) – launched April 7, 2025 at a 30% discount to Soliris’ WAC
Market data suggests Soliris offers minimal to no rebate, making biosimilar conversion particularly attractive. For plans not receiving rebates, switching to Epsyqli could save over $200,000 per patient annually.
As with other high-cost biologics, early and proactive transition strategies, whether under the medical or pharmacy benefit, are recommended to capture the lowest net cost, ensuring financial sustainability and fiduciary responsibility.
Legislative Updates: Trump Admin’s Executive Order
At the federal level, the White House announced a new Executive Order outlining changes aimed at lowering prescription drug costs, focusing largely on improving transparency, competition, and middleman reform. While many of the directives are Medicare-focused, several could directly impact employer-sponsored pharmacy benefits and commercially insured members. Much of the language in the report centers on evaluations and early-stage recommendations, while concrete action still remains uncertain.
Below is a summary of the topics outlined in the executive order that may specifically impact commercial plan sponsors and members:
- PBM Fee Transparency: The Department of Labor will propose new regulations to improve fiduciary transparency for employer health plans by requiring disclosure of direct and indirect PBM compensation. This may empower plan sponsors to better assess PBM contracts and identify hidden fees.
- 340B Access for the Uninsured & Underinsured: Federally Qualified Health Centers may soon be required to offer insulin and epinephrine (generic EpiPen) at or below 340B prices (plus minimal fees) to low-income individuals with high cost-sharing, unmet deductibles, or no insurance, potentially reducing emergency medication costs for some employees and dependents.
- Generic/Biosimilar Acceleration: A directive to fast-track FDA approval of generics and biosimilars could increase competition and drive down drug costs, benefiting employer plans through lower net costs over time. The report also includes a directive aimed at improving the process through which prescription drugs can be re-classified as over the counter (OTC) medications. The report does not yet provide specifics on how these timelines or processes will change from current standards.
- Importation Streamlining: The Secretary, through the Commissioner of Food and Drugs, is directed to simplify the drug importation process, potentially allowing states to bring in lower-cost medications from abroad, paving the way for future employer participation if authorized.
- Middleman Reform: The administration will reevaluate the role of PBMs and other intermediaries to promote a more competitive and transparent pharmaceutical supply chain. This could lead to regulatory shifts affecting rebate pass through and spread pricing practices.
Oral GLP-1: Wins and Losses
Just days apart, Pfizer and Eli Lilly shared markedly different updates on their investigational oral GLP-1 therapies. Both products, danuglipron (Pfizer) and orforglipron (Lilly), are first-in-class small molecule, non-peptide GLP-1 receptor agonists. Unlike traditional injectable GLP-1s, which are large, modified human peptides, these oral drugs do not mimic the GLP-1 structure but still activate the GLP-1 receptor to produce similar clinical effects.
- Pfizer announced on April 14th that it would halt development of danuglipron after a clinical trial participant experienced drug-induced liver injury. The condition resolved after discontinuation of the drug.
- Eli Lilly, on the other hand, reported positive Phase 3 results for orforglipron on April 17th. The drug showed statistically significant efficacy and a safety profile comparable to injectable GLP-1s in trials for both type 2 diabetes and weight loss. Lilly plans to submit for FDA approval for weight loss by the end of 2025 and for type 2 diabetes in 2026, which makes orforglipron the likely next edition to the list of GLP-1s on the market. The company also addressed supply concerns, stating they are prepared for a global launch without supply constraints. No pricing information has been released at this time.
So how does orforglipron stack up against current GLP-1s? While direct head-to-head trials are still needed for a true comparison, the table below summarizes clinical trial outcomes for orforglipron alongside other leading GLP-1 therapies on the market.
