TiGenix (OTC:TGXSF) just announced, a bit earlier than anticipated, the 6-month interim results from its ongoing Phase 1/2 trial of AlloCSC-01. The therapy uses cardiac stem cells sampled from donors (allogeneic therapy) and administered via intracoronary infusion to patients suffering from acute myocardial infarction (AMI). The injection occurs within 5 to 7 days following the AMI.
The trial enrolled 51 patients, split 2:1 into two groups - 34 patients receiving active therapy and 17 on placebo, in addition to best standard of care for all patients. The primary objective of the trial is to demonstrate the safety of the allogeneic therapy and to look for signs of efficacy on several parameters, with an interim analysis due after 6 months (present results) and full results delivered after 12 months of follow up.
The interim results after 6 months showed that:
- Safety is fine to this date (no death and no significant adverse event, or MACE, in the treatment arm) which was the primary objective of the trial
- Besides, the only efficacy parameter analyzed to this date (change of infarct size) did not show a significant difference between control and active arms
Some thoughts about these elements:
The good safety profile of the therapy is not a surprise in itself, but it is nevertheless a must to continue clinical developments; that's a good thing done.
The only efficacy parameter that was computed for this interim analysis is the change of infarct size, which does not in itself reflect a direct improvement in the state of patients. Obviously, it's a shame that it was not possible to show a significant treatment effect, yet, at this preliminary stage. However, for comparison, previous trials of stem cell therapies in heart disease patients such as Celyad's (NASDAQ:CYAD) (C-Cure) and Capricor's (NASDAQ:CAPR) (CAP-1002) were focused on showing improvements in left ventricular ejection fraction (LVEF), end-systolic and end-diastolic volumes (ESV, EDV). These are measurement of blood volumes ejected and remaining into the heart after contraction and those parameters are correlated with functional improvements and healthier patients - chronic heart disease is linked to the diminished efficacy of the "heart pump", so higher volumes of blood ejected (and lower volumes retained) are considered significant improvements. In TiGenix's trial, these parameters will be measured after 12 months and announced with the final results which should be released in Q1-2017.
In brief, are these results good or bad news?
The main interest of the trial will lie within the data regarding the above-mentioned parameters (LVEF, ESV, EDV) which will be compared to other similar therapies - it will give a good idea of the opportunities for further developments of the product. At this stage, these data are not yet available - hence, it would be premature to draw any conclusion about the efficacy profile of the therapy. Obviously, it would have been better for TiGenix to be able to announce outstanding efficacy right now... given the limited data available at this stage, nothing can be said about that and so, the news should not generate a big upside. The final 12-month analysis remains the real game-changer here.
One must also keep in mind the context of heart disease therapies: at the moment, there is no satisfying alternative to treat patients with chronic heart failure except for very costly (and risky) procedures such as heart transplant or LVADs and even modest improvements observed with a very safe cell therapy is considered worthy of further development - e.g. Celyad's C-Cure showed an absolute 7% (or 25% relative) increase in LVEF and this was judged convincing enough to conduct a large Phase 3 trial, which is poised to deliver results by the end of June.
Another fact is that stem cell therapies are still partially understood despite years of clinical development, which can lead to surprising results. For example, while Athersys' (NASDAQ:ATHX) MultiStem (allogeneic bone marrow-derived stem cells) did not show significant efficacy after 3 months in a Phase 2b stroke trial, 12-month follow up results demonstrated a significant improvement in the recovery of treated patients.
Finally, even though success in cutting edge clinical research is never certain, the advantage of TiGenix over similar small-cap biotechs is that it can rely on a mostly de-risked asset, Cx601, justifying a strong fundamental value at this point. Clearly, AlloCSC-01's success would be a great upside, but even in case of failure, TiGenix's value should not be lastingly affected. At the moment, TiGenix's cash investment in AlloCSC-01 is strictly limited - $1 million in cash to acquire the asset (plus $6 million in stock) and no additional commitment in case of failure, a very reasonable bet for a fully enrolled Phase 2 clinical product. Hence, waiting for the 12-month readout should not be worrisome given the continued progress made with other assets.
Update: After discussing the results with the company, I am sharing here some clarifications received from IR.
At this interim analysis, only the mean absolute change in infarct size (% left ventricular mass), standard deviation and 95% confidence intervals from baseline to 6 months were analysed.
Why is that so? Because CAREMI, being a first-in-human of AlloCSC-01, it is an "open" clinical study for the 6 First Patients (the Dose Ranging part of the trial or phase I). For this part of the study we were able to obtain data on Safety and Efficacy of the intracoronary infusion of AlloCSC-01 (PR 23 of Sept 2015). However the study is also comprised of a second phase (the randomized part of the study) which will be kept blind until 12 months (to be precise this is the Double Blind part of the study, whereas both patients, doctors and of course the company do not know to which group the patient belongs).
The "Double Blind" applies to the randomized part of the study whereas the safety and efficacy data of 49 patients recruited in this second phase (plus the 2 patients recruited during the escalation phase) for a total of 51 patients will be kept blind until 12 months. Again, to be clear, the only parameters analysed at six-months were the mean absolute change in infarct size (% left ventricular mass), standard deviation and 95% confidence intervals from baseline to 6 months were analysed. All other efficacy MRI and clinical parameters will be analysed during the final analysis at 12 months.
Until then no speculation can be done on efficacy at all and it would be incorrect to do so at this point.
Disclosure: I am/we are long TGXSF, CYAD.