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BOSTON – Four novel medications approved by the FDA in 2024 have the potential to significantly impact primary care practices, addressing common conditions like resistant hypertension, urinary tract infections (UTIs), menopausal hot flashes, and a prevalent form of liver disease, according to a presentation at the American College of Physicians (ACP-IM) Internal Medicine Meeting 2025.
Dr. Gerald W. Smetana, professor of medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, highlighted these first-in-class drugs – aprocitentan, sulopenem etzadroxil plus probenecid, fezolinetant, and resmetirom – as particularly relevant for internists among the six such medications approved last year.
Aprocitentan: A New Option for Resistant Hypertension, But Costly
Resistant hypertension, defined as blood pressure remaining above goal despite using three medications including a diuretic, affects roughly 12% of hypertensive patients. Aprocitentan, a dual-endothelin receptor antagonist, showed statistical superiority over placebo in reducing blood pressure in the PRECISION trial involving patients on standardized background therapy.
However, Dr. Smetana noted the absolute effect was “relatively modest.” Mild to moderate edema was the most common side effect. Significant barriers include its potential teratogenicity, requiring enrollment in a risk mitigation program, and its high cost – estimated around $800 compared to $5-$15 for existing alternatives like labetalol or spironolactone. Dr. Smetana recommended trying these older, cheaper drugs first before considering aprocitentan as a potential fourth-line agent.
Sulopenem: Tackling Tough UTIs, With Resistance Concerns
Uncomplicated UTIs are a mainstay of primary care, and rising antibiotic resistance presents challenges. With quinolones facing safety concerns (tendinopathy, neuropathy), the new oral carbapenem combination, sulopenem etzadroxil plus probenecid, offers a potential alternative, particularly for infections resistant to other drugs.
Studies showed sulopenem was noninferior to ciprofloxacin and amoxicillin/clavulanate in treating uncomplicated UTIs in women, with notable benefit against ciprofloxacin-resistant strains. However, diarrhea was more common (8.9% vs ~3%). Approved in October 2024 but not yet available, its cost is unknown. Dr. Smetana urged cautious use within its approved indication to prevent resistance development, adding that cost will likely be another significant barrier.
Fezolinetant: A Non-Hormonal Approach to Hot Flashes
While hormone replacement is effective for menopausal hot flashes, safety concerns limit its use. Fezolinetant offers a novel non-hormonal mechanism, binding to the same receptor as estrogen but without the associated risks.
Clinical trials (SKYLIGHT 1 & 2) demonstrated significant reductions in both the frequency and severity of hot flashes compared to placebo in women aged 40-65 experiencing at least seven per day. The benefit was sustained for at least a year. Importantly, Dr. Smetana highlighted that post-marketing reports of rare severe liver injury necessitate liver function test monitoring for patients taking fezolinetant.
Resmetirom: A Breakthrough for Fatty Liver Disease (MASH)
Resmetirom marks a significant advance as the first approved treatment for metabolic dysfunction–associated steatohepatitis (MASH) – the progressive form of fatty liver disease – in adults with moderate to advanced liver fibrosis. This thyroid hormone receptor agonist works by regulating liver fat metabolism.
In clinical trials, significantly more patients taking resmetirom experienced resolution of MASH or improvement in liver fibrosis at 52 weeks compared to placebo. Nausea and diarrhea were the most common side effects, occurring about twice as often as with placebo. Despite its “game changer” potential for a disease affecting a large population, its hefty price tag (approx. $47,700/year) and limited long-term outcome data (expected 2027) are major considerations. Dr. Smetana suggested that, for now, prescribing should likely remain with hepatologists, although its relevance to primary care may grow.
Primary Care Perspective and Barriers
Dr. Neil Skolnik, professor of family and community medicine at Thomas Jefferson University, commented that fezolinetant and resmetirom are likely to have the biggest immediate impact. He called fezolinetant an “important addition” providing an effective, well-tolerated non-hormonal option for hot flashes, stressing the need for liver enzyme monitoring.
Regarding resmetirom, Dr. Skolnik emphasized its importance as the first MASH treatment, highlighting the need for primary care physicians to identify patients with MASH, even though treatment initiation will likely require referral to a specialist. He echoed concerns about cost and access being universal barriers for new medications.
Disclaimer: This news article is based on information presented by Dr. Gerald W. Smetana at the American College of Physicians (ACP-IM) Internal Medicine Meeting 2025, as summarized in the provided text. It is intended for informational purposes only and does not constitute medical advice. Consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment. Financial disclosures for the experts cited are mentioned in the source material.
