An Endocrine News roundup of the week’s pharmaceutical news, breakthroughs, and general information. *
FDA Approves First in Class Targeted Therapy for Metastatic Pancreatic Cancer
On August 26, the U.S. Food and Drug Administration (FDA) approved Rasonque (daraxonrasib), a RAS inhibitor for the most common form of pancreatic cancer—delivering a new treatment option to patients with advanced pancreatic cancer months ahead of schedule.
Rasonque, a tablet taken once daily, targets multiple forms of a protein called RAS, a key driver of tumor growth in most patients with pancreatic adenocarcinoma, which arises from cells lining the ducts of the pancreas.
“Today’s approval provides a critical new option for patients facing an extraordinarily difficult and historically hard-to-treat cancer. It is our fundamental duty to deliver more cures and meaningful treatments to patients as quickly as possible,” said Acting FDA Commissioner Kyle Diamantas, J.D. “I am immensely proud of the dedicated FDA scientists whose fast, thorough review and relentless commitment made this groundbreaking milestone a reality.”
The approval is for the treatment of adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy.
Approximately 90% to 95% of the 67,000 new cases of pancreatic cancer diagnosed in the United States each year are pancreatic adenocarcinoma, according to the National Cancer Institute. Despite representing roughly 3.2% of all cancer diagnoses, pancreatic adenocarcinoma accounts for a disproportionately high share of cancer deaths, owing to its typically late detection, aggressive disease course, and historically limited treatment options.
In a randomized, open-label, multicenter clinical trial involving 500 adults with previously treated metastatic pancreatic adenocarcinoma, Rasonque improved median overall survival to 13.2 months compared to 6.7 months for standard chemotherapy.
“This drug showed unprecedented results in an area of high unmet need,” said Angelo de Claro, M.D., director of the FDA’s Oncology Center of Excellence. “The approval was granted 6.5 months before the user fee deadline, demonstrating the FDA’s commitment to accelerating the approval of new cancer treatments for patients with serious and life-threatening conditions.”
The FDA granted Rasonque Breakthrough Therapy and Orphan Drug designations. Rasonque received Priority Review for this indication. The application was also reviewed under the Commissioner’s National Priority Voucher pilot program, which is intended to help accelerate the review of therapies that address national public health priorities.
In May, the FDA issued a “safe to proceed” letter allowing the sponsor to initiate an expanded access treatment protocol for Rasonque, enabling patient access to the investigational drug prior to approval under applicable FDA regulations.
The most common side effects of the drug are rash, diarrhea, stomatitis (inflammation of the mouth’s mucus membranes), nausea, fatigue, vomiting, abdominal pain, edema, decreased appetite, and hemorrhage.
The FDA granted the approval to Revolution Medicines, Inc.
FDA approves Lilly’s Mounjaro (tirzepatide) to Reduce Cardiovascular Risk in Adults with Type 2 Diabetes
On August 28, Eli Lilly and Company announced that the U.S. Food and Drug Administration (FDA) approved Mounjaro (tirzepatide), a dual GIP and GLP-1 hormone receptor agonist, to lower the risk of major adverse cardiovascular (CV) events (MACE), including CV death, non-fatal heart attack, or non-fatal stroke in adults with type 2 diabetes who are at high risk for these events.
Mounjaro is already approved as an adjunct to diet and exercise to improve blood sugar in adults and children 10 years of age and older with type 2 diabetes.
“Heart health deserves attention throughout the course of treatment, not just after a serious cardiovascular event. While a large portion of type 2 diabetes care is focused on glucose control, mitigating cardiovascular risk is essential and can be overlooked.”
David A. D’Alessio, MD, study co-author and director of the Division of Endocrinology and Metabolism at Duke University School of Medicine
“For people with type 2 diabetes, heart disease is the leading cause of death, and Mounjaro … now gives them a proven way to lower that risk, adding to the strong foundation it has already built in A1C and weight,” said Kenneth Custer, PhD, executive vice president and president, Lilly Cardiometabolic Health. “We set a higher bar by testing Mounjaro against a GLP-1 medicine with proven cardiovascular benefit, one that reflects the depth of evidence Lilly continues to build in this field.”
The approval was based on results from SURPASS-CVOT, the first cardiovascular outcomes trial comparing two incretin medicines head-to-head rather than against a placebo, and the largest and longest tirzepatide study to date, enrolling more than 13,000 participants across 30 countries over more than four and a half years. In the trial, Mounjaro demonstrated non-inferiority to Trulicity (dulaglutide), a GLP-1 treatment with established cardiovascular benefit, with an 8% lower rate of cardiovascular death, heart attack or stroke (MACE-3). The estimated hazard ratio for time to first MACE was 0.92 (95.3% CI: 0.83, 1.01) for Mounjaro compared to Trulicity (dulaglutide).
“Heart health deserves attention throughout the course of treatment, not just after a serious cardiovascular event,” said Endocrine Society member David A. D’Alessio, MD, study co-author and director of the Division of Endocrinology and Metabolism at Duke University School of Medicine. “While a large portion of type 2 diabetes care is focused on glucose control, mitigating cardiovascular risk is essential and can be overlooked. This approval gives patients a medicine that reduces the risk of cardiovascular events and supports metabolic health at the same time.”
The safety and tolerability of Mounjaro were generally consistent with its established profile. The most commonly reported adverse events in SURPASS-CVOT for Mounjaro were gastrointestinal-related, generally mild-to-moderate in severity, and occurred primarily during the dose-escalation period. Please see Indications and Safety Summary with Warnings below and full Prescribing Information and Medication Guide.
For more information about Mounjaro, please visit www.Mounjaro.lilly.com.
