Interview with Bioheart CSO, Kristin Comella including on FDA

I invited the Chief Scientific Officer (CSO) of Bioheart, Kristin Comella, to do an interview after hearing some buzz that this could be a critical time for the company and that it might have been recently visited by the FDA.

Note that Comella not just Bioheart CSO, but also the primary instructor for physician training in stem cell methods offered by the company US Stem Cell Training.

Can you update us on how Bioheart is doing with its clinical trials/INDs?

Comella: Our completed clinical trials of MyoCell to date have been primarily targeted to patients with severe, chronic damage to the heart who are in Class II or Class III heart failure according to the New York Heart Association, or NYHA, heart failure classification system. We have completed various clinical trials for MyoCell including the SEISMIC Trial, a 40­patient, randomized, multicenter, controlled, Phase II­a study conducted in Europe and the MYOHEART Trial, a 20­patient, multicenter, Phase I dose­escalation trial conducted in the United States. We were approved by the FDA, to proceed with a 330­patient, multicenter Phase II/III trial of MyoCell in North America and Europe, or the “MARVEL Trial”. Thus far, 20 patients, including 6 control patients, have been treated. Initial results for the 20 patients were released at the Heart Failure Society of American meeting, showing a significant (35%) improvement in the 6 minute walk for those patients who were treated, and no improvement for those who received a placebo. On the basis of these results, we have applied for and received approval from the FDA to reduce the number of additional patients in the trial to 134, for a total of 154 patients. The SEISMIC, MYOHEART, and MARVEL Trials have been designed to test the safety and efficacy of MyoCell in treating patients with severe, chronic damage to the heart.

In addition, we  received approval from the FDA to conduct a Phase I safety study on 15 patients of a combined therapy (MyoCell with SDF­1) called the REGEN trial. Advancement of the MyoCell and MyoCell SDF­1 clinical development programs is contingent, among many factors, upon the Company obtaining access to sufficient funding to execute the necessary clinical trials to achieve proof of efficacy and regulatory authorization to market such products.

Bioheart has spent over $125 million researching cellular therapies for patients and supporting clinical trials. We are committed to bringing more treatments forward and all revenue that is brought into the company is put towards advancing this science. Our FDA phase 3 MARVEL Trial for congestive heart failure patients is budgeted to cost $10 million dollars for 100 patients. Trying to complete double blind placebo controlled trials is very expensive and there is limited funding for companies who are trying to complete these trials.

How did you and Bioheart get interested in stem cell training courses for MDs? Is US Stem Cell Training owned by Bioheart? Is there some common ground between the missions of the two?

Comella: We are currently offering courses for physicians through US Stem Cell Training which is a wholly owned subsidiary of Bioheart. The field of regenerative medicine is expanding very rapidly and physicians may not have adequate exposure to these topics during medical school. Our goal is to provide physicians with the latest research in cellular medicine. The course includes didactic lecture and hands on demonstration with topics including:

• Stem Cell Biology
• Embryonic Cells
• Induced Pluripotent Stem Cells
• Bone Marrow Stem Cells
• Adipose Stem Cells
• Platelet Rich Plasma
• GMP Training
• Regulatory Environment
• Fat Harvesting Procedure
• Bone marrow isolation Procedure

The course is constantly updated with new research and data as more studies are published. The goal is to familiarize physicians with the latest research and how this may affect their practice. We also host a monthly webinar series which includes journal clubs and guest lecturers. This field is growing and we want to provide physicians an opportunity to learn more about regenerative medicine. Many patients are asking their physicians questions about regenerative medicine and our hope is to bridge the gap between basic research and clinical practice.

What are your views on the recent FDA draft guidances including on adipose in which the FDA suggested that SVF is a biological drug?

Comella: The FDA has recently released a draft guidance document regarding the use of human cell and tissue products used during the same surgical procedure from adipose tissue and has requested comments from the public on this guidance. Please note that guidance documents represent the FDA’s “current thinking on the scope” of the topic. “FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the FDA’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in FDA’s guidances means that something is suggested or recommended, but not required.”

We do not believe that the current draft guidance document will affect our ability to offer in-clinic cell therapy from fat to our patients. We understand that the FDA’s draft document has elicited much resistance from the public and highly respected organizations such as AABB Center for Cellular Therapies and The Academy of Regenerative Medicine have voiced their opposition.

It is impossible to predict what the FDA will do regarding any in clinic therapies so I can only tell you what has happened in the past. In December of 2014, the FDA visited our lab as well as three physicians who are doing SVF procedures. The FDA took no action against anyone and did not stop the SVF procedures. Many of you have seen that these procedures can provide benefit to patients who have failed other therapies. Our primary goal has been and will continue to be safety and well-being for our patients.

Oftentimes, emerging technologies are met with skepticism and criticism. When stents were first introduced as an option for patients having a heart attack, many famous cardiologists criticized them because of the risk of restenosis (blockage). Yet stenting is now a common cardiac procedure. Cellular medicine has existed since the 1960s and is commonly used for cancer patients under the term Bone Marrow Transplant. These treatments were never put through double blind placebo controlled trials; nevertheless, we accept them as the standard of care. In addition, cellular medicine for degenerative diseases has been the subject of thousands of animal studies and clinical trials. Many of these studies date back to the 1980s. I think a fair question to ask a patient who has failed to benefit from traditional medicines and therapies is “how many studies would you like to see before you try to harness your body’s own healing potential”. Most patients are willing to try something experimental and, provided that companies are clear on the possible risks versus rewards, these therapies should not be withheld from the public.

I think that the body’s natural healing mechanisms are fascinating. The ability to harness this natural healing potential to reverse the effects of degenerative diseases or injuries is very powerful. We have a lot to learn about regenerative medicine but we are now starting to realize the potential by bringing these therapies to clinic. With any new therapies, there are challenges to bringing them to market. In addition, it is difficult to navigate the regulatory environment because these therapies are unlike any others currently available to patients. Cellular therapies should not be regulated in the same way as drugs and devices and many regulatory bodies are trying to establish new rules and guidelines. I am not sure that a person’s own cells should be regulated in the same way as a drug that is manufactured. It is important to advance science with patient safety as the primary interest. We have treated patients whose lives have completely changed for the better because of regenerative medicine and this is why I love this field!

Was US Stem Cell Training or Bioheart recently visited by the FDA? If so, how did the visit go and could you please provide a copy of the 483 form?

Comella: In December of 2014, we had an unannounced inspection from the FDA of our lab as well as three physicians who are doing SVF procedures. The FDA requested copies of our protocols and information about all of the materials that are utilized in the SVF process. They also specifically requested information regarding several IRB protocols. The FDA toured our lab facilities as well as the facilities of three different physicians. The FDA took no action against anyone and did not stop the SVF procedures. No warning letters (i.e. 483s) were issued. We received notice that all the documents were sent to CBER who reviewed and at this time they have no additional questions. Therefore the investigation was closed. Please note that this is the second investigation for Bioheart and we have not received any warning letters (483s). Our lab is a registered FDA tissue bank (FEI: 3005825762) and we are subject to unannounced FDA inspections.