Catch up on some of the latest decisions and approvals from the FDA.
The US Food and Drug Administration has been busy in recent times. Find out what they’ve been up to.
Advisory panel endorses multi-cancer blood test
The Molecular and Clinical Genetics Devices Panel of the Medical Devices Advisory Committee of the FDA has voted favourably for the Premarket Approval (PMA) application of the Galleri multi-cancer early detection test.
“The Galleri test is designed to detect cancer-specific methylation patterns shared by many types of cancer before symptoms appear, including cancers that do not have recommended screening today,” said Grail, the biotech company behind the new test, in a statement.
“When a cancer signal is detected, Galleri is designed to predict the cancer signal origin with high accuracy to help guide diagnostic evaluation. The test is intended to be used in addition to, and not as a replacement for, guideline-recommended screenings.”
The 10 voting members on the committee deliberated and handed down their verdict on three separate questions:
- There was “reasonable assurance” that Galleri is safe to use (10-0 in favour)
- There was “reasonable assurance” that Galleri was effective (6-4)
- The benefits of Galleri outweighed the risks (7-2, with one abstention).
However, more than one voting member of the panel were not fully convinced about the real-world benefits of the Galleri test.
“Clearly, there are clinically impactful results of the test,” Dr Jason Dominitz from the VA Puget Sound Health Care System in Seattle, Washington, told MedPage Today. “People get a diagnosis work-up, cancers are found, but does that lead to clinically clinical benefit? I don’t see that we have evidence of clinical benefit at this time.”
Adjunct Professor Stanley Lipkowitz, a medical oncologist and researcher from the National Cancer Institute, also had concerns about the potential clinical effectiveness of the test.
“As an oncologist, I generally look at that as outcome, and we don’t have that data,” he told MedPage Today.
Other members were uncomfortable with the use of the word “early” in Grail’s branding and promotion of the test.
“It can detect things early … earlier than maybe we would find in some circumstances. But is that clinically relevant?” MedPage reported Professor Victor van Berkel, MD PhD from UofL Physicians in Louisville, Kentucky as saying. “I would say no, but I think the truest answer is I don’t know that we know the answer to that.”
The current application was based on the 12-month follow-up data from the PATHFINDER 2 study, along with data from the first-year screening round of the NHS-Galleri trial. Both trials showed similar results in terms of episode sensitivity (35.0% and 31.6%), specificity (99.85% and 99.74%), negative predictive value (99.07% and 98.89%), and cancer signal origin prediction accuracy (94.3% and 91.9%), but were further away on positive predictive value (77.0% versus 66.2%).
Grail CEO Joshua Ofman MD MSHS said the vote reinforced the strength of Galleri’s clinical evidence.
“The Galleri test was developed to improve the effectiveness and efficacy of our national cancer screening program by adding multi-cancer early detection to recommended screening – helping find more cancers safely, when they may be easier and less costly to treat, and it still may be possible for a patient to receive treatment with curative intent,” he told media.
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“We believe the panel’s recommendations reaffirm a high evidence bar that Gral has set for a multi-cancer early detection test. Grail is committed to working with the FDA as it completes its review of Galleri, the first PMA submission for a multi-cancer early detection test.”
The FDA frequently follows advice of the advisory panel, even though it is not required to. Galleri is already available in the US as a laboratory-developed test. FDA approval could trigger broader coverage and use of the test. A final decision on the PMA is expected to be announced in the coming months.
Combination therapy for renal cell carcinoma gets thumbs up
Last month the FDA approved the use of belzutifan (Welireg, Merck & Co) and lenvatinib (Lenvima, Eisai) in adults with advanced renal cell carcinoma with a clear cell component following a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor.
The efficacy of the belzutifan/lenvatinib combination was assessed in the LITESPARK-011 trial, which saw 747 patients (565 males) with advanced renal cell carcinoma with a clear cell component from 184 medical centres across 25 countries receive either the combination or cabozantinib.
After a median follow-up of 29.0 months, progression-free survival was significantly longer in the belzutifan/lenvatinib group compared to the cabozantinib group (14.8 months versus 10.7 months). However, there was no difference between the two arms with respect to overall survival (34.9 versus 27.6 months).
Serious treatment-emergent adverse events (grade 3 or higher) occurred at similar rates between the two groups, reported in 84% of patients receiving belzutifan/lenvantinib and 83% of patients receiving cabozantinib. Hypertension was the most common adverse event, affecting 31% of patients in the combination group and 29% in the cabozantinib group. The treatment-related adverse events resulted in three deaths, two of which were among patients who received belzutifan/lenvatinib.
Belzutifan is listed on the Australian Register of Therapeutic Goods for the following indications: adults with von Hippel-Lindau disease who require therapy for associated renal cell carcinoma, central nervous system haemangioblastomas, or pancreatic neuroendocrine tumours not requiring immediate surgery; and adults with advanced renal cell carcinoma with a clear cell component following PD-1/L1 and a vascular endothelial growth factor-targeted therapy.
Lenvatinib has received TGA approval for a variety of oncological indications, including endometrial carcinoma (in combination with pembrolizumab), differentiated thyroid cancer, advanced renal cell carcinoma (in combination with pembrolizumab or everolimus), and unresectable hepatocellular carcinoma.
However, use of the belzutifan/lenvatinib combination has not been approved by the TGA. Eisai were unable to comment on current or future regulatory plans as they were not the sponsor of the LITESPARK trials, while MSD did not respond to requests for comment by publication deadline.
New treatment option for cholangiocarcinoma patients
The FDA has announced its approval of lirafugratinib (Lyrfigtu, Elevar Therapeutics, Inc) for the treatment of adults with previously treated unresectable, locally advanced, or metastatic cholangiocarcinoma that contains a fibroblast growth factor receptor 2 (FGFR2) gene fusion or rearrangement.
Lirafugratinib is an oral small molecule inhibitor of FGFR2, a receptor tyrosine kinase that is commonly altered in certain cancers.
The FDA’s decision comes after lirafugratinib was granted a priority review designation in March 2026 and was guided by the results of the phase 1/2 ReFocus trial. One hundred and sixteen patients with cholangiocarcinoma took part in the ReFocus trial. Forty-six percent of patients treated with lirafugratinib saw significant reductions to the size of their tumours, with the response lasting a median of 11.8 months. Median progression-free survival was similar (11.3 months).
Serious adverse reactions occurred in 32% of patients taking lirafugratinib, with infection (6.0%), pneumonia (3.4%), fatigue (2.6%), and haemorrhage (2.6%) the most common serious reactions. Other common adverse reactions included nail toxicity, stomatitis, alopecia, retinal pigment epithelial detachment, constipation, and decreased appetite.
Associate Professor Lipika Goyal, director of gastrointestinal oncology at the Stanford Cancer Center and lead author on the ReFocus study, said the FDA decision would provide patients with advanced bile duct cancer an important precision medicine option.
“Lyrfigtu’s unique, irreversible, covalent-binding mechanism enables potent and sustained inhibition of FGFR2, including many resistance mutations that can emerge with earlier FGFR inhibitors. And unlike earlier pan-FGFR inhibitors, it selectively targets FGFR2 while minimizing off-isoform toxicities,” she told media.
Lirafugratinib is expected to be available to patients in the US before the end of 2026. Elevar’s media contact, Rosemary Ostmann from RoseComm, said regulatory submission plans for jurisdictions outside the US and Europe were currently under review.
Cholangiocarcinoma is considered a rare cancer due to the number of people it affects. Approximately 1300 Australians are diagnosed with cholangiocarcinoma each year, with roughly two thirds of diagnoses occurring in people aged 65 years and older.
Once-weekly injectable approved for T2D
Finally, the FDA has also approved insulin efsitora alfa-gobe (Onswik, Eli Lilly) for use in adults living with type 2 diabetes.
Insulin efsitora alfa-gobe is a once-weekly basal insulin injection designed to be used in conjunction with diet and exercise. Eli Lilly claims it can lead to more than 300 fewer injections over the course of the year compared to using daily insulin injections.
The results of the QWINT phase 3 trials – a quartet of trials involving more than 3000 patients where insulin efsitora alfa-gobe was compared to insulin glargine or degludec – informed the FDA’s decision. Insulin efsitora alfa-gobe resulted in a non-inferior A1c reduction compared to insulin glargine and degludec while demonstrating a similar safety profile.
Common side effects associated with insulin efsitora alfa-gobe include hypoglycaemia, allergic reactions, reactions at the injection site, lipodystrophy at the injection site, itching, rash, swelling of the hands and feet, and weight gain.
“Onswik offers a new once-weekly basal insulin option for patients and reflects our continued commitment to deliver innovative treatment options that expand choice and provide greater flexibility in how people manage type 2 diabetes,” said Kenneth Custer, executive vice president and president of Lilly Cardiometabolic Health.
The FDA is the fourth regulatory body to approve insulin efsitora alfa-gobe for use in adults with type 2 diabetes, joining the European Medicines Agency, the Federal Commission for the Protection Against Sanitary Risks (Mexico), and the Pharmaceuticals and Medical Devices Agency (Japan).
Eli Lilly did not respond to questions regarding plans to submit insulin efsitora alfa-gobe for regulatory approval in Australia prior to the publication deadline.
