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Powerhouse | Case Study Title
HCG has guided more than 180 teams through United States Food and Drug Administration (FDA) Advisory Committee Meetings, European Medicines Agency (EMA) Oral Hearings, and Scientific Advisory Group meetings – all with an impressive 81% success rate. Our expert scientists, strategists, regulatory, and communications professionals, medical writers, designers, editors, and project managers have the experience to successfully navigate critical regulatory interactions.
Our Expertise
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Securing Accelerated Approval With a Failed Trial and Unproven Surrogate Endpoint
Situation
The pivotal trial in a rare neurodegenerative disease failed to meet its primary endpoint, and the sponsor chose to seek accelerated approval based on a novel biomarker that was not established as a surrogate endpoint reasonably likely to predict clinical benefit in this disease.
Strategy
We helped the sponsor team develop a strong argument for the validity of the surrogate endpoint by supplementing modeling data with a large body of literature linking the novel biomarker with clinical measures in the proposed indication and related neurodegenerative diseases.
We recommended that the sponsor present data demonstrating that failure on the primary clinical endpoint was due, in part, to the study design not adequately controlling for heterogeneity in the patient population. We also advised the sponsor team to leverage post hoc analyses showing that baseline levels of the biomarker were a reliable predictor of disease progression when used as a stratification factor.
We brought in a well-respected external KOL to help make the case that the treatment effects observed in the pivotal trial were clinically meaningful
Results/Outcome
The advisory committee voted unanimously in favor of Accelerated Approval, and this first-in-class drug was approved for use, giving hope to patients and their families dealing with a devastating neurodegenerative disease. The advisory committee also indicated that the ongoing confirmatory trial will be important to validate the surrogate endpoint.
Overcoming Skepticism Regarding the Unmet Medical Need and Clinical Benefit of a New Treatment
Situation
Mock advisory committees were skeptical about the unmet medical need in patients with transfusion-dependent anemia associated with a chronic blood disorder and expressed concern that the novel therapy had modest clinical benefit with short duration of response, might worsen quality of life, and could increase the risk of disease progression.
Strategy
To drive home the unmet need, we developed a visual patient journey to clearly establish where this new therapy fit in the treatment armamentarium and the limitations of existing therapies. We also superimposed the findings from the pivotal trial onto graphical presentations of historical data to visualize how the new therapy reduced transfusion rates over time without increasing the risk of disease progression.
To put the efficacy data into perspective, we highlighted data showing multiple episodes of response and cumulative duration of response to demonstrate meaningful clinical benefit over time.
We placed the patient-reported outcomes (PRO) data into the context of the disease and engaged PRO experts to clearly communicate the appropriate interpretation of the findings.
Results/Outcome
The key messages and materials created during AdCom preparation were used extensively during FDA interactions. After the late-cycle review meeting, the FDA decided to cancel the AdCom, and the product was subsequently approved. It has since become a new standard of care.