Exelixis pulls a surprise win in thyroid cancer just days ahead of final Cabometyx readout
Exelixis added a thyroid cancer indication to its super-seller Cabometyx’s label on Friday — months before the FDA was expected to make a decision, and days before the company was set to unveil the final data at #ESMO21.
At a median follow-up of 10.1 months, differentiated thyroid cancer patients treated with Cabometyx (cabozantinib) lived a median of 11 months without their disease worsening, compared to just 1.9 months for patients given a placebo, Exelixis said on Monday.
The pivotal trial, dubbed COSMIC-311, enrolled 258 patients from a small but desperate patient population: those whose disease progressed following treatment with vascular endothelial growth factor receptor (VEGFR)-targeted therapy, and who are refractory to or ineligible for radioactive iodine.
Only about 5% to 15% of thyroid cancer patients are resistant to radioiodine treatment, but with a lack of available treatments, they are only expected to live three to five years after diagnosis.
“Before today, patients with radioactive iodine-refractory differentiated thyroid cancer who have progressed following prior VEGFR-targeted therapy were facing aggressive disease and no standard treatment option,” principal investigator Marcia Brose said in a statement.
The final COSMIC-311 analysis comes three months after Exelixis uncorked the interim data, which suggested Cabometyx reduced patients’ risk of disease progression or death by 78% compared to placebo after about six months. But despite hitting the mark on progression-free survival, the drug failed a co-primary endpoint of objective response rate in the first 100 randomized patients at 6 months, coming in at just 15%. Across the whole intent-to-treat population, that figure is lower at just 11%, Exelixis announced on Monday.
Exelixis didn’t say much about that endpoint in its news release, and CEO Michael Morrissey was not available for an interview before press time.
The company’s stock $EXEL was down about 5% on Monday, pricing in at $19.67 apiece.
Cabometyx was first approved for second-line kidney cancer in 2016, two years after a prostate cancer failure forced Exelixis to lay off 70% of its staff. The company’s recent strategy has been pushing combination treatments and regulatory filings to expand its list of approved indications. Last year, Cabometyx raked in $718.7 million in the US.
Regulators granted the drug breakthrough therapy designation back in February, and assigned a PDUFA date of Dec. 4. But the agency unexpectedly came forward with an OK a whole three months early. The label includes patients 12 years and older.
Among the most common Grade 3 or 4 side effects seen in COSMIC-311 was palmar-plantar erythrodysesthesia, a condition that causes redness, swelling and pain in the hands and feet. Other side effects included hypertension, fatigue, diarrhea, and hypocalcemia. No treatment-related deaths were reported.
“We would like to thank the clinical trial participants, the physicians and their staff who participated in the COSMIC-311 trial and to acknowledge the team at the FDA for their collaboration during the quick review of our application,” Morrissey said in a statement.
In 2016, Ipsen struck a deal with Exelixis for exclusive development and commercialization rights to Cabometyx outside of the US and Japan. Takeda has the rights in Japan, which it snapped up in 2017.
This article has been updated to clarify points made about the design of the study.