Hazards

Last week we discussed benefit:risk evaluations which requires understanding of the risks, which are defined by a process called a Hazard Analysis.

The Hazard Analysis is a systematic consideration of every known and imaginable harm – extending from patient safety to corporate viability. The word “imaginable” is intentional. When developing a unique therapy there are always unknowable factors. For each hazard, the severity and frequency are estimated along with a risk mitigation plan. Creating and updating this analysis allow the drug developer to prioritize attention to those with greatest risks,

RB-190 Related Hazards

Instead of providing the complete Hazard Analysis, I’ll share two Hazards that are part of our focus. This is not complete information for either; my goal is to reveal how a Hazard Analysis is managed.

The drug. Initially the analysis focused on how we could obtain the drug (metyrosine), including the costs. We learned that the manufacturers were not interested in supplying or partnering with us, so the analysis shifted from focusing on the commercial drug supply chain to identifying a drug manufacturer.

That meant our focus started with the drug substance – the actual chemical and then to its formulation into tablets and their manufacture. It also raised questions about the manufacture of matched placebo tablets.

We’ve reached the point where we consider those hazards to be managed successfully. We’ve successfully manufactured the tablets and matched placebos for use in the clinical trials and completed the initial testing of the final product. Hazards shift as the development program advances.

Biologic/toxicologic risk. Before a drug can be used in clinical trials, a range of laboratory testing is required to evaluate potential adverse effects. These laboratory studies are standardized and include the need to study the drug’s effects in large mammals (yes, dogs typically) for 6 months and then separately for 9 months. At the end of each, the animals are euthanized and their internal organs examined. When the active chemical in RB-190 was first approved, only 6-month studies were required.

During our discussions with the FDA, they told us that before we could treat people with this drug beyond 6 months, we needed to conduct those 9-month studies in dogs. Our Hazard Analysis includes the risk of such a requirement to the company’s development program, as this would require several million dollars to complete these tests. And more importantly, whatever the plan, we need to prove to ourselves  whether the drug was sufficiently safe to use as a treatment for longer than 6 months.

We developed an approach that the FDA appeared willing to consider in place of the additional dog studies. In the future I’ll share more details. We are nearing completion of a study using real world data that seems likely to satisfy the Agency. And the preliminary results indicate that patients, doctors and the team at Right Brain Bio will be confident about the safety of RB-190 beyond 6 months of use.

Summary

Understanding hazards is important. Assuming any hazard is a showstopper makes transformation harder. Instead, we’re using the Hazard Analysis both to imagine risks and to imagine solutions. Some risks eventually go away, as did the risk of a reliable source of drug, which was replaced by risks associated with manufacturing our own drug. We’re addressing those risks now.

Risks can appear insurmountable, but by looking at them from different angles, looking for ways that similar hurdles were overcome by others and breaking down a risk into smaller components, potential solutions emerge.