Our Meeting with the FDA
In this Blog I want to discuss a few things about our Oxycyte meeting with the FDA.
Going into our October meeting with the FDA in Rockville, MD , we felt that there were some safety issues concerning Oxycyte that we would have to overcome. In the meeting, we provided additional data and were able to clearly convey the message that there are medically compelling reasons to evaluate a potentially beneficial therapeutic intervention against the effects of traumatic brain injury (TBI) because this is an area of terribly unmet medical need.
Our doctors told the meeting that the TBI numbers are just frightening: Civilian TBI is the biggest cause of loss of life or ability in the population that is work-force age. Cancer and heart disease strike at older ages while TBI impacts younger people. Of those who suffer a TBI, only about 25-30% survive, and of those, 50% end up with major impairments and will never be able to do what they did before their injury.
Although our Phase 2A study only had a small number of patients treated with our drug, we had a 50% improvement in patients with good, moderate, and severe outcomes compared to the control group. That is certainly promising. Yet due to the small number of patients enrolled, those results can not be statistically relevant. That study was conducted to provide a basis for additional clinical investigation.
In the FDA meeting, we pointed out that our compound has no adverse effects that could not be addressed during treatment. The agency focused on thrombocytopenia – low platelet count that can lead to impaired blood clotting and spontaneous bleeding. Our response was that, while it is a serious adverse event, this effect is well under control in patients with TBI because it is already constantly monitored and if platelets drop below a certain number, a platelet transfusion is usually given anyway to avoid risk of additional bleeding.
As a result of our presentation in the October 22 meeting, the agency asked us to submit additional data for consideration of our clinical plan. They requested three action items for further information and data about thrombocytopenia in our nine patients. The data the agency requested goes beyond the data directed by the test protocol and extends to the entire hospitalization experience of the patients. While this data was not called for collection by the clinical protocol, it is now considered potentially helpful to the agency and to us in assessing the patients’ treatment experience and confirming the safety profile of Oxycyte. We have been going through the hospitalization and treatment files to compile this data and will be including it in our submission.
The idea for the dose escalation study became obvious after discussing safety data from our Phase 1 study. In that early safety study, there was no significant drop in platelet count with a dose of 0.5ml/kg body weight. However, we have more current animal data showing efficacy of Oxycyte in smaller doses. A dose escalation study allows the step-wise evaluation of increasing dose levels of a drug. Systematically, doses are increased and safety is evaluated until effects recommend going back to the previous dose. Then the previous dose is repeated. This is done until enough data is collected to conclude what the most effective safe dose will be. After every step, the safety data is analyzed. This approach should reveal a lot of information more quickly than a traditional double-blind Phase 2B study. I’m hopeful that it will also provide the information that potential licensing partners are waiting for.
Our filing with the response to the agency’s request for information will include a synopsis of the dose escalation protocol we propose. We intend to submit that filing later this month and plan to issue a news release to let you know that the filing has indeed been submitted. After our filing is received, the agency has 30 days to review it and respond to us. If they agree to allow clinical investigations to resume but respond with recommendations for changes or other suggestions, we will then incorporate their findings and then submit (what we hope will be) the final version of the dose escalation protocol. Then, the agency again has 30 days to respond. We will be able to resume clinical investigations when FDA gives a clear agreement with our clinical plan.
Meanwhile, to facilitate progress on the development path for Oxycyte, we are formatting our filings in such a way that they could also be submitted in Canada and in Switzerland. This is a development path taken by many pharmaceutical companies to be able to conduct multinational clinical trials to accelerate clinical development and get robust clinical data that can be representative of more widespread populations of TBI patients.
In parallel we are working on our topical indications as we continue to pursue our goal of getting the company on its own funding feet as soon as possible. We’re making investments in this area because they have what I see as real potential to provide the money to fund our continued development in TBI as well as other areas. I’ll cover more on our progress in topical treatments in future blogs.