8-K: Actinium's Iomab-B Faces Regulatory Hurdle, Additional Trial Required by FDA

The FDA has determined that Actinium's Phase 3 SIERRA trial for Iomab-B is insufficient for BLA filing, requiring an additional head-to-head trial demonstrating overall survival benefit.

Summary

• Actinium Pharmaceuticals has received a regulatory update from the FDA regarding its Biologics License Application (BLA) for Iomab-B.
• The FDA has determined that the Phase 3 SIERRA trial, despite meeting its primary endpoint of durable Complete Remission (dCR) with a p-value of <0.0001, is not sufficient to support a BLA filing.
• The FDA requires an additional head-to-head randomized clinical trial demonstrating an overall survival benefit with Iomab-B.
• This new trial will compare allogeneic bone marrow transplant (BMT) using Iomab-B plus a reduced intensity conditioning regimen of fludarabine and total body irradiation (Flu/TBI) versus allogeneic BMT using reduced intensity conditioning comprised of cyclophosphamide plus Flu/TBI.
• The new study will not allow patients to crossover from the control arm, unlike the SIERRA trial where nearly 60% of patients crossed over.
• Actinium plans to request a meeting with the FDA to discuss the specifics of the additional trial and will seek a strategic partner for Iomab-B in the U.S. after these interactions.
• The company will now focus development efforts on Actimab-A, Iomab-ACT, and preclinical programs.

Sentiment

Score: 3

Explanation: The document conveys a negative sentiment due to the FDA's rejection of the SIERRA trial results for BLA filing and the requirement for an additional clinical trial. This setback will likely delay the commercialization of Iomab-B and require additional resources.

Positives

• The SIERRA trial met its primary endpoint of durable Complete Remission (dCR) with a p-value of <0.0001.
• The SIERRA trial demonstrated positive secondary endpoints including Event Free Survival (EFS) and safety.
• Actinium has built strong relationships with key thought leaders through the SIERRA trial.
• The SIERRA trial data were presented in 12 oral presentations at several leading medical conferences.
• Actinium has a strong track record in manufacturing, supply chain, clinical development, and operations.

Negatives

• The FDA has determined that the SIERRA trial is not adequate to support a BLA filing for Iomab-B.
• An additional head-to-head randomized clinical trial is required to demonstrate an overall survival benefit.
• The SIERRA trial did not meet the secondary endpoint of overall survival on an intent to treat basis due to a high crossover rate of nearly 60%.

Risks

• The need for an additional clinical trial will likely delay the BLA filing for Iomab-B.
• Securing a strategic partner for Iomab-B in the U.S. may be challenging.
• The new clinical trial may not produce the desired results.
• There are risks and uncertainties associated with clinical trials, regulatory clearances, and market demand for Actinium's products.

Future Outlook

Actinium will seek a strategic partner for Iomab-B in the U.S. and focus development efforts on Actimab-A, Iomab-ACT, and preclinical programs. The company will also work with the FDA to determine the specifics of the required additional clinical trial.

Management Comments

• Actinium's Chief Medical Officer, Dr. Avinash Desai, stated that they will work with the FDA to discuss the specifics of the proposed randomized head-to-head clinical study.
• Actinium's Chairman and CEO, Sandesh Seth, expressed disappointment that the positive results from the SIERRA trial were not deemed adequate by the FDA to support a BLA filing.

Industry Context

The requirement for an overall survival endpoint in AML therapies reflects a broader trend in the industry where regulatory agencies are increasingly prioritizing this outcome for drug approvals. This decision impacts Actinium's development timeline and strategy for Iomab-B.

Comparison to Industry Standards

• The FDA's decision to require an overall survival endpoint aligns with the current trend in AML therapy approvals, where most recent approvals have been based on achieving a positive overall survival endpoint.
• The SIERRA trial's design, which allowed for physician's choice of salvage therapies and heterogenous conditioning regimens in the control arm, differs from the FDA's requirement for a head-to-head comparison with a specific conditioning regimen.
• The high crossover rate in the SIERRA trial, where nearly 60% of control arm patients received Iomab-B followed by a BMT, is a significant factor in the FDA's decision, as it confounded the overall survival analysis.

Stakeholder Impact

• Shareholders may experience a negative impact due to the delay in the BLA filing for Iomab-B.
• Patients with r/r AML may experience a delay in access to Iomab-B.
• Employees may be impacted by the shift in development priorities.

Next Steps

• Actinium will request a meeting with the FDA to discuss the specifics of the additional clinical trial.
• Actinium will seek a strategic partner for Iomab-B in the U.S.
• Actinium will focus development efforts on Actimab-A, Iomab-ACT, and preclinical programs.

Key Dates

Keywords

Iomab-B, BLA, FDA, clinical trial, AML, bone marrow transplant, radiotherapy, Actinium, SIERRA trial, overall survival, durable Complete Remission, strategic partner