Aytu BioPharma has announced the signing of an exclusive agreement with Fabre-Kramer Pharmaceuticals to commercialize EXXUA (gepirone) extended-release tablets in the United States, marking the company's entry into the over $22 billion US prescription major depressive disorder market. EXXUA represents the first-in-class oral selective serotonin 5HT1a receptor agonist approved by the FDA for treating MDD in adults.
Novel Mechanism Addresses Unmet Medical Need
EXXUA distinguishes itself from existing antidepressants through its unique mechanism of action. The drug's antidepressant effect is believed to be related to its modulation of serotonin activity and its exclusive, strong binding affinity for 5HT1a receptors, which serve as key regulators of mood and emotion. Unlike selective serotonin reuptake inhibitors (SSRIs), EXXUA has no reuptake inhibition activity.
Dr. Stephen Stahl, Professor of Psychiatry at the University of California and founder of the Neuroscience Education Institute, emphasized the drug's significance: "EXXUA is the first truly selective agonist of the serotonin 1a receptor that has been consistently linked to mediation of mood disorders and suicide risk. It's an important addition to the armamentarium to treat depression."
Clinical Evidence and Safety Profile
EXXUA has been extensively studied in over 5,000 patients across clinical trials, demonstrating significant improvement in depression symptoms. Notably, the incidence of sexual side effects experienced with EXXUA was comparable to placebo, making it the only antidepressant acting on serotonin receptors that does not carry label warnings about the risk of sexual dysfunction.
The drug also exhibits no significant adverse effects on weight, blood pressure, heart rate, or liver function, addressing common concerns associated with current MDD treatments. This safety profile is particularly relevant given that over 340 million antidepressant prescriptions were written in 2024 in the United States, yet significant unmet needs remain due to unacceptable side effects associated with current therapeutics.
Strategic Commercial Opportunity
Josh Disbrow, Chief Executive Officer of Aytu, described the licensing agreement as "a transformative milestone for Aytu and a significant advancement for patients suffering from major depressive disorder." The company has undergone a strategic pivot over the past two years to focus on its core prescription business while seeking to acquire differentiated, branded CNS products.
"Given the compelling and novel product profile of EXXUA and the unmet needs of MDD patients, we believe EXXUA can become a very important treatment option for the over 21 million Americans affected by MDD," Disbrow stated.
Stephen Kramer, M.D., Co-Founder and Chief Executive Officer of Fabre-Kramer Pharmaceuticals, noted that EXXUA was developed to address important unmet needs he witnessed first-hand managing MDD patients for decades as a practicing psychiatrist. "While therapeutic advancements have been made, issues such as treatment emergent sexual dysfunction and weight gain persist as problematic side effects of many MDD treatments," Kramer explained.
Financial Terms and Launch Timeline
Under the agreement terms, Aytu paid Fabre-Kramer Pharmaceuticals an upfront payment upon closing and will pay an additional fixed payment at the one-year anniversary of the EXXUA launch date. The company will also pay royalties on net revenue, along with a product transfer price, and make variable, performance-based milestone payments upon achieving various net revenue thresholds.
The transaction is being funded by cash on hand along with financing led by long-term, healthcare-focused institutional investors, including Aytu's largest shareholder Nantahala Capital Management, Stonepine Capital Management, Aytu management, and new institutional shareholders.
Aytu is actively preparing to launch EXXUA in the United States and currently anticipates pharmacy and patient availability in the fourth calendar quarter of 2025. The company expects EXXUA to serve as a major growth catalyst and centerpiece of its commercial efforts, leveraging its sales force's CNS focus and proprietary Aytu RxConnect patient access platform.
Safety Considerations
EXXUA carries important safety warnings, including a boxed warning about increased risk of suicidal thoughts and behaviors in pediatric and young adult patients. The drug is not approved for use in pediatric patients. Additional safety considerations include potential QT prolongation, serotonin syndrome when taken with certain other medicines, and potential manic episodes in people with bipolar disorder.
