An inaugural edition of the mailbag. Questions are block formatted. Allons-y…
"I read with interest your article. Everybody has the right to his opinion, but coming from someone with your background, who worked for the mayo clinic for years in the field of myocardial remodeling, your opinion carries particular weight for me."
The findings from your own research should carry the most weight. The articles on this website are personal opinion sprinkled with a few weak jokes.
“1) You have worked at mayo till august 2014. You must be aware that mayo clinic is a shareholder of cardio3. Did you meet doctors … during your period when you were at mayo clinic to discuss your skepticism? What intrigues me is your tweet, published on june 4th 2013 where you say, i quote “I read the recently published paper. My advice would be to stay far away”. You were at Mayo Clinic at that time, is your opinion based only on the lecture of the paper or other knowledge you have from working at Mayo Clinic?”
I have not collaborated with any investigators in any research relating to bone marrow derived regenerative cell therapies. I gather my information from Pubmed and The Google and render my own opinion. My skepticism or optimism is irrelevant to the efforts of this or any company. Collaborations and licensing deals that companies may have with each other are their own responsibility; I only know what is publicly disseminated.
"2) Have you also written this message (broken link) I ask the question because your twitter account points to the username poorgradstudent . Are you suggesting that the trial is a giant bust?"
The Twitter handle is linked on this site. Apologies, but your other link did not work for me.
“3) Concerning the results of the C-Cure trial, if the trial demonstrated a 7% increase in the LVEF for the 21 treated patients, what made me invest in cardio3 is the fact that ALL of the treated patients have seen an increase in the LVEF as is shown in the table in the published results. This seems to be statistically significant. Does your analysis take into account the fact that the Chart-1 trial uses C-Cathez (this was not the case during the phase 2 trial) with a much higher cell retention rate? Or the fact that that Chart-1 trial has an inclusion criteria of LVEF ≤ 30% while the phase 2 had an inclusion criteria of LVEF ≤ 40%, knowing that the best results are obtained when the LVEF is the lowest? My conclusion is that the results of Chart-1 may be superior to the results of the phase 2 trial.”
I only considered what was described in the C-Cure trial. I can not make extrapolations based on how different those results would be when repeated with another catheter. Similarly, I can not make extrapolations based on LVEF groupings.
“4) You say, i quote “only 21 of the 32 ITT patients were included in the efficacy analysis on a per-protocol basis ends up on weaker footing than if the efficacy analysis was completed on an ITT basis (...) Cardio3 will face similar challenges in their registrational phase III trials. However, they are unlikely to convince regulators if they deviate away from an ITT trial analysis. All told, there is reason to be highly cautious of extrapolating the C-Cure results into expectations for Chart-1 and -2”.
That is true, 2 patients were excluded because they did not meet clinical inclusion criteria and no bone marrow was harvested, 2 were excluded because they did not meet bone marrow inclusion criteria and declined repeat bone marrow harvest, and 7 were excluded as quality control inclusion criteria were not met and declined repeat bone marrow harvest. But Christian Homsy said, if i recall well, at the Investor Day on January 30, 2015, that the percentage of patients that can’t have their bone marrow harvested adequately was driven down from 25% in the phase 2 trial to 13% and even 8% after repeat harvesting. Don’t you think a 92% success rate is sufficient?”
I do not know what harvesting percentage is sufficient. My comment was simply based on the considerations one must make when reading an intent-to-treat analysis versus a per-protocol analysis.
“5) You say, I quote “The claim is that the interactions with the FDA are the cause, specifically a change in the primary endpoint of the trial. Curious. Perhaps this timing gives outsiders a view into the confidence expressed by the company”.
It is true that Cardio3 is pushing back patient enrollment for Chart-2. But there may be another reason: Cardio3 wants to obtain FDA approval to use C-Cathez in order to obtain a higher cell retention rate and better results. And to obtain this approval they need the futility results from Europe? This is a mere conjecture that I make, I might be mistaken, but what do you think of this alternative?”
Comments relating to this point can be heard on the webcast of the Investor’s Day presentation. They mention a delay due to interactions with the FDA, primarily relating to the trial endpoints. I accept this to be accurate. I do not have any conjecture to make about the choice of catheter in use, and do not know if or how that impacts their FDA interactions.
“6) You must know that Chart-3 will soon start in china and a trial in japan. If the investors in Cardio3 didn’t believe in it why would they be constructing a 10,000 square feet stem cell GMP production facility in Hong Kong alongside a 10,000 square feet medical center with state-of-the-art equipment? I invite you to visit their web site: http://www.medisun.hk/”
Since they require facilities to generate their cell-based therapy, I don’t consider the construction / establishment of these facilities to have any bearing on the prospects of their trials. I consider these facilities simply to be a necessity for their work.
Note: The excerpts from the email were edited for clarity, and names of individuals not employed by Cardio3 were removed. Also, a few spelling corrections were presumptively made.
Comments and questions welcome.