CROSSJECT’s ZEPIZURE® EUA Filing: A Lifesaving Breakthrough or Regulatory Hurdle?

CROSSJECT (CRO.PA) has reached a critical juncture in its bid to secure Emergency Use Authorization (EUA) for ZEPIZURE®, its needle-free auto-injector for treating status epilepticus, a life-threatening seizure condition. With final manufacturing data expected as soon as June 2025, the company is poised to deliver a potential game-changer in emergency epilepsy care—if it can navigate the FDA’s review process. Here’s why investors should pay close attention.

Manufacturing and Regulatory Progress: A Tight Timeline

CROSSJECT’s collaboration with CDMO partner EUROFINS has advanced steadily. By May 2025, all aseptic filling steps for ZEPIZURE® registration batches were complete, with final batch release data slated for delivery in June. Once integrated into the regulatory dossier, BARDA—the U.S. agency funding the project—will submit the application to the FDA. Initial FDA feedback on dossier completeness is expected within a month of submission, with authorization potentially following shortly thereafter.

The stakes are high: a positive EUA decision would fulfill a $60 million BARDA contract to supply ZEPIZURE® to the U.S. CHEMPACK program, a national stockpile for chemical threat preparedness. CEO Patrick Alexandre emphasized the milestone’s significance, stating it validates the ZENEO® platform as a disruptive drug-delivery technology.

Efficacy and Clinical Data: Proven in Practice

ZEPIZURE®’s efficacy is underpinned by the landmark RAMPART study, which established intramuscular midazolam as the gold standard for pre-hospital seizure management. Published in Neurology and Therapy (2024), Crossject’s bioequivalence trial confirmed ZEPIZURE’s reliability: it delivered midazolam with 50% lower variability in absorption compared to intranasal formulations, ensuring faster, more consistent seizure termination.

A Phase 1 trial in 2025 will further validate its bioequivalence to existing IM midazolam syringes, a critical step for FDA approval. Stability data is also robust, with batches showing 36-month shelf life, easing supply chain logistics for CHEMPACK and future commercialization.

Market Opportunity: Addressing a Critical Gap

Status epilepticus afflicts 40% of U.S. epilepsy patients—up to 4 million annual seizures—yet current treatments like nasal sprays often fail in real-world emergencies. ZEPIZURE’s auto-injector design eliminates the need for venous access or clinical expertise, making it usable by first responders or caregivers.

The CHEMPACK contract alone guarantees early revenue, but the broader addressable market is vast. If approved, ZEPIZURE could carve a niche as the “EpiPen of epilepsy”, targeting both emergency settings and long-term patient management. Analysts estimate the global market for acute epilepsy treatments could exceed $1.5 billion by 2027, driven by rising awareness and unmet needs.

Risks and Challenges: The Path Ahead

While progress is encouraging, risks remain. Manufacturing delays—already pushing the timeline to Q2 2025—could strain resources. Competition is fierce: nasal sprays like Valday (Zogenix) and generic midazolam syringes dominate the market. ZEPIZURE must prove its usability advantage in head-to-head trials.

Regulatory hurdles are another concern. While EUA approval is faster than full FDA approval, the agency may demand additional safety data or restrict labeling. CROSSJECT’s reliance on BARDA for submissions also introduces execution risk, as bureaucratic delays could prolong the timeline.

Conclusion: A Transformative Moment for CROSSJECT

CROSSJECT’s ZEPIZURE® stands at the intersection of medical need and innovation. With a $60 million BARDA contract secured, a proven safety profile, and a design superior to existing therapies, the EUA approval could unlock a $1.5 billion market. If successful, ZEPIZURE’s 36-month shelf life and auto-injector platform could also open doors to therapies for allergic shock and adrenal insufficiency, extending the company’s pipeline.

However, execution is key. The June 2025 manufacturing deadline and FDA’s swift feedback window (one month post-submission) leave little room for error. Investors should monitor:
- FDA submission and feedback timelines
- Phase 1 trial results by mid-2025
- Manufacturing scale-up for CHEMPACK deliveries

If CROSSJECT clears these hurdles, ZEPIZURE could redefine emergency epilepsy care—and position the company as a leader in next-generation drug delivery. The stakes are life-saving, and the opportunity is enormous.