The path forward: What comes after a CRL?

This blog post is the last in our series about the Complete Response Letters (CRLs) that the U.S. Food and Drug Administration (FDA) issued to Sanofi for tolebrutinib to treat non-relapsing secondary progressive multiple sclerosis (nrSP-MS) on December 23, 2025, and to Corcept Therapeutics for relacorilant to treat Cushing syndrome on December 30, 2025. Both drugs are included in the Clarivate “Drugs to Watch 2026” report, and these decisions came after the report was finalized.

In the wake of a CRL from the FDA, companies like Sanofi and Corcept Therapeutics face critical decisions about next steps. Historical precedent about CRLs suggests both of their drugs, tolebrutinib and relacorilant, have pathways to eventual approval, through additional evidence generation, refined risk management strategies or repositioning to different patient populations. Most drugs receiving CRLs eventually gain approval, though timelines vary widely based on required remediation.

The path forward for tolebrutinib

Sanofi’s path forward depends largely on addressing drug-induced liver injury (DILI) risk, potentially leveraging data from the failed primary progressive multiple sclerosis (PP-MS) study. The FDA noted that, after Sanofi switched to weekly liver monitoring, no additional cases of DILI resulting in death or transplant occurred, suggesting monitoring intensity matters. Sanofi has stated it “strongly believes in the risk-benefit profile of tolebrutinib ,” indicating the company intends to pursue resubmission. The expanded access program requested by FDA indicates continued dialogue, which often precedes successful resubmissions.

In addition, a narrower label might be required, shrinking the eligible population to just nrSP-MS without active MRI. The FDA noted that nrSP-MS patients with evidence of MRI lesion activity should be considered “active SP-MS” (relapsing) and therefore eligible for the many disease-modifying therapies already approved for relapsing patients. However, with this narrower population, HERCULES data alone might not actually show sufficient benefit.

The path forward for relacorilant

Corcept’s pathway appears more straightforward, as the CRL didn’t cite fundamental safety nor efficacy concerns. CEO Joseph Belanoff stated Corcept is “confident we will find a way to get relacorilant to the patients it could help.” The company plans to meet with FDA to determine required next steps, which could potentially include re-analysis of existing phase 3 data to focus on select subgroups or a new phase 3 trial (which could result in significant delays).

The simultaneous pursuit of ovarian cancer approval provides both revenue potential and additional evidence generation. If approved for this indication, relacorilant would be the first drug to market with its mode of action and the first to demonstrate improvement in overall survival.

Regulatory setbacks as part of the drug development lifecycle

The CRLs for tolebrutinib and relacorilant underscore a fundamental tension in drug development: the imperative to bring needed therapies to patients quickly must be balanced against ensuring those therapies are safe and effective. While these developments affect the companies, investors and patients awaiting new treatment options, they reflect a regulatory system working as designed.

For the broader pharmaceutical industry, these cases reinforce that being a “drug to watch” doesn’t guarantee smooth regulatory sailing despite reflecting genuine commercial and therapeutic promise. Transforming scientific innovation into approved medicines requires not just clinical evidence but also strategic regulatory navigation, comprehensive safety characterization and, often, resilience in the face of setbacks.

The AI-powered advantage for rapid decision-making

Companies can remain more agile in the unpredictable life sciences landscape by using trusted, integrated industry intelligence powered by artificial intelligence (AI), such as that provided by Clarivate solutions:

Democratize access across functional teams: Natural language interfaces enable regulatory, clinical, and commercial teams to explore complex questions without technical barriers, providing sophisticated intelligence critical to all functions.
Accelerate decision timelines: When responding to CRLs, time is a competitive advantage —every month of delay allows competitors to advance. Clarivate AI-powered solutions — from regulatory agents to competitive intelligence analytics — transform time-consuming manual analysis into rapid, source-validated insights for confident decision-making.
Ensure strategic coherence: Coherent resubmission strategies rely on integrated analysis of regulatory precedents (Cortellis Regulatory Intelligence), clinical trial design optimization (Cortellis Clinical Trials Intelligence), real-world evidence for differentiated positioning (DRG Fusion), competitive dynamics (Cortellis Competitive Intelligence) and market forecasting (Disease Landscape and Forecast).
Navigate regulatory complexity: In the global pharma landscape, companies often need to navigate not only FDA requirements but also parallel submissions in other regions. The comparative jurisdictional analysis in Clarivate solutions helps manage divergent regulatory pathways, evidence requirements and political dynamics across global markets while ensuring compliance and auditability.
Maintain auditability: The Clarivate approach to transparent AI links the outputs directly to the source documents so that every insight, recommendation, and strategic decision can be traced to authoritative sources. This visibility is essential for regulatory submissions where evidence provenance matters.

From setback to strategic advantage

CRLs represent significant setbacks, but they don’t determine ultimate success. With the right intelligence, strategic insights and evidence generation capabilities, both Sanofi and Corcept Therapeutics can address the FDA’s specific concerns and transform the regulatory feedback into focused development strategies. The Clarivate integrated, AI-powered suite of solutions offers precedent analysis to turn regulatory challenges into opportunities for building even stronger cases for approval — ultimately serving the patients with nrSP-MS and Cushing syndrome who await these potentially transformative therapies.

Learn more about our 2026 Drugs to Watch , and you can read about how Clarivate is using AI tools to empower its clients to make better decisions faster.