One Drug Halted, Another Advances

Novartis halted enrollment in its Phase 1 trial of IAG933 in late 2025 and removed the asset from its pipeline presentation. A company spokesperson said the decision was based on the project’s tolerability and antitumor activity, and not on safety concerns. At ESMO 2025, IAG933 had shown a 19% overall response rate across 37 people with Hippo-altered tumors and roughly 13% to 17% in 30 people with pleural mesothelioma. This leaves VT3989 as the leading TEAD inhibitor for mesothelioma.

TEAD inhibitors target a key pathway in mesothelioma. When the tumor suppressor NF2 is lost (40-50% of cases), TEAD proteins drive uncontrolled cell growth. Blocking TEAD can stop this growth. The approach is mesothelioma-specific, oral, and has a clear biomarker (NF2 status).

VT3989 has shown 32% response rate, 86% disease control, and 40-week median progression-free survival (vs 15 weeks historical). It has received FDA Fast Track designation and is advancing to Phase 3 trials starting in 2026, with potential approval around 2029-2030.

Ask your oncologist about VT3989 trials, search ClinicalTrials.gov for “TEAD mesothelioma,” consider NF2 testing to determine eligibility, and contact Vivace Therapeutics directly for trial information.

Numerous FDA-approved drugs have been withdrawn from the U.S. market when post-approval data showed risks outweighed benefits, such as rofecoxib (Vioxx) in 2004 due to increased heart attack and stroke risk ,. Other examples include sibutramine (Meridia) in 2010 for cardiovascular risks, lorcaserin (Belviq) in 2020 for cancer risk, and ranitidine (Zantac) in 2020 due to carcinogenic contamination. Since the 1970s, at least 35 such drugs have been pulled, often after years on the market, for issues like severe heart toxicity or birth defects ,. The FDA maintains an official list of withdrawn products for safety reasons.

Drug antagonism occurs when one drug reduces or blocks the effect of another drug through mechanisms such as receptor binding, where an antagonist occupies the receptor’s active site to prevent agonist binding ; pharmacokinetic interactions, which alter the second drug’s absorption, distribution, metabolism, or elimination ; or chemical reactions that inactivate the ligand before it reaches the receptor. Competitive antagonists can be overcome by increasing the agonist dose, while non-competitive or irreversible types cannot. These interactions are documented in pharmacology resources, including peer-reviewed analyses of drug combinations.

No FDA-approved drugs for mesothelioma have been withdrawn or discontinued. Thousands of drugs have been approved by the FDA since 1938, but only a small fraction. fewer than 100 notable cases. have been withdrawn worldwide, mainly due to safety issues like cardiac risks (e.g., rofecoxib in 2004), hepatotoxicity, or carcinogenicity (e.g., ranitidine in 2020). People with mesothelioma use ongoing treatments like pemetrexed or nivolumab, none of which appear on FDA withdrawal lists as of 2026. Discontinued drugs often differ from those in current shortages, which stem from manufacturing issues rather than safety. For the latest status, check FDA resources directly.

Bextra (valdecoxib), an NSAID pain reliever manufactured by G.D. Searle & Co., was withdrawn from the market in April 2005 after just three years of availability. The FDA removed it due to serious cardiovascular adverse events including death, myocardial infarction, and stroke, as well as increased risk of severe skin reactions like Stevens-Johnson syndrome and toxic epidermal necrolysis. The agency determined that Bextra offered no advantage over other available NSAID pain relievers, making its safety risks unjustifiable. This case illustrates how drugs approved by the FDA can later be found to pose unacceptable risks during post-market use, with the median time from approval to withdrawal being approximately five years.