Repositioning Failure: Corcept's Dazucorilant and the ALS Survival Gamble

The biotech sector thrives on turning setbacks into strategic pivots, and Corcept Therapeutics (NASDAQ: CORT) now finds itself at a crossroads with its experimental ALS therapy, dazucorilant. While the Phase 2 trial missed its primary endpoint of slowing functional decline in amyotrophic lateral sclerosis (ALS), the data revealed a striking survival advantage at the 300 mg dose—a signal that could reframe the drug's future. This article explores how Corcept might leverage this survival data, its regulatory Fast Track status, and existing cash flows from its approved drug Korlym to create a high-risk, high-reward opportunity for investors.

The Primary Endpoint Miss: A Setback, Not a Death Knell

The Phase 2 DAZALS trial enrolled 249 ALS patients randomized to 150 mg dazucorilant, 300 mg dazucorilant, or placebo. The primary endpoint—slowing functional decline using the ALSFRS-R scale—was not met. Functional decline rates were statistically similar across all groups at 24 weeks, a result that initially sent Corcept's stock down 20% on the news. However, buried in the data was a survival signal so strong it could redefine the drug's trajectory.

Survival Data: A Lifeline for Dazucorilant

At week 24, no deaths occurred in the 300 mg group (n=83), while the placebo group (n=82) had five deaths (p=0.02). By one year, the survival advantage widened: the hazard ratio (HR) for death in the 300 mg group versus placebo was 0.16 (p=0.0009), meaning patients on dazucorilant had an 84% lower risk of death. This is a landmark result in a disease where median survival is just 2–5 years.

The data hints at a paradigm shift: survival, not functional metrics, could become the new gold standard for ALS drug approval. Corcept is now engaging regulators to argue that this endpoint should be the primary focus of Phase 3 trials—a strategy that could bypass the ALSFRS-R hurdle.

Regulatory Pathways: Fast Track and the Survival Endgame

Corcept holds FDA Fast Track designation for dazucorilant in ALS, a status granted in December 2024. This accelerates interactions with the FDA, enabling rolling review of data and potential accelerated approval. While the company has not secured Orphan Drug designation (a gap in the provided data), ALS's classification as a rare disease (affecting ~55,000 people in the U.S. and EU) could still qualify dazucorilant for such a designation, providing market exclusivity and tax incentives.

The key milestone is March 2025, when full one-year survival data from the ongoing extension study—where all patients received 300 mg dazucorilant—will be reported. If the survival benefit persists, Corcept could propose a Phase 3 trial with survival as the primary endpoint, a design that could be fast-tracked to approval.

Why Investors Should Care: Risk and Reward

The stock's valuation reflects skepticism: Corcept trades at just $15–$20, far below its peak of $50 in 2021. Yet two factors make it intriguing:
1. Korlym's Cash Flow: Corcept's approved drug for hypercortisolism generates ~$150 million in annual revenue, funding R&D without dilution.
2. Survival's Clinical Impact: A drug that delays death by months—or years—could command blockbuster pricing in ALS, a market with few effective therapies.

The Bottom Line: A High-Stakes Gamble

Corcept's stock is a high-risk, high-reward play. The March 2025 data readout is a binary event: if survival holds, the stock could surge 100–200%. If not, the company may pivot to other indications or face further setbacks. For investors with a long-term horizon and tolerance for volatility, the survival data's potential to redefine ALS treatment makes CORT a compelling contrarian bet.

Investment Takeaway: Buy CORT at current levels if you believe survival endpoints will gain regulatory acceptance in ALS. Set a tight stop-loss ahead of the March data, and monitor regulatory discussions closely. The risk is steep, but the reward—a drug that could extend life in a terminal disease—is life-changing.

Disclosure: This analysis is for informational purposes only and not a recommendation to buy or sell securities.