EQUIPOISE: A concept worth being aware of!
There has been a fascinating debate on this and the other CYP threads about the potential negative impacts that a Ryoncil label extension/expansion might have on a Cynata's clinical trial involving the same target group (the patients who otherwise qualify to access Ryoncil). I will try and add to the debate, more from the research principles end of town. I hope it helps.
Firstly, in the presence of an incumbent (such as Ryoncil), there will still be a regulatory pathway for Cynata's competing product, or anyone else's, for that matter. That may be now, or after a period of exclusivity if that applies. That path will be via:
a) The new entrant proving equivalence (or non inferiority): This is sufficient for regulatory approval. Or,
b) The new entrant proving superiority (if they have what it takes): This helps with market capture (the best-in-class phenomenon!).
How do you do the above? A head-to-head Randomised Control Trial (RCT) is the gold standard for proving equivalence or superiority, so where feasible, this would be ideal. However, many trialists avoid these for reasons that include the risk that comes from relying on a competitor's product being available during your trial! Instead, Cynata could do an indirect type trial by simply replicating the methodology/template provided (used) by Mesoblast in its trials - vs whatever Ryoncil was compared against. Getting the same or better results could be good enough for Cynata to present towards an approval. A discussion of the protocol with the FDA is essential. Indeed, a head to head can still be done later.
Other issues that people are raising on the feasibility of this will generally get covered under the ethics approval process. This is where compelling Phase 1 and 2 data come in handy. It is, after-all, unethical even for the ethics committee to act in a way that protects an incumbent when a potentially better product is available. A larger comparative study becomes a priority, thanks to the growing body of evidence: Phase 1/2 trials, and publications such as the one shared a few days ago.
What if Ryoncil has become the standard of care by the time a trial starts (someone mentioned this)? I would hope that this will also mean that availability of Ryoncil has been scaled up to make a head to head less risky.
Will Doctors Recruit for a Cynata trial when Ryoncil is available? If
equipoise exists and ethics approve - absolutely! Clinical equipoise is an ethical principle that says that a doctor should only participate in an RCT if, based on available evidence, they are genuinely uncertain about which therapy is better. Those who are convinced that the existing therapy (such as Ryoncil), is superior, should not participate in an RCT that can end up denying some patients the treatment that the doctor knows to be the better one: they should continue prescribing Ryoncil. The data that Cynata bring to the table are the driver that creates the state of
equipoise!
The Ethics Committee Role is worth discussing, specifically! It is these men and women, who assess the risk-benefit balance, including issues mentioned by some posters, such as potential delays in treatment (e.g., if Cynata’s therapy requires a 2-day waiting period compared to some standard therapy). If the committee approves the trial, it means that the risk is deemed acceptable. Shareholders need not worry!
What if Cynata gets squeezed out? Well, they could try areas or populations that have limited or no access to funded Ryoncil, and prove themselves out there. A well designed trial, that produces stunning results, will be noticed even by the FDA!
Yes, the FDA! Who gets FDA Fast Track Designation?
- Serious Condition & Unmet Need: The designation is granted to drugs that treat serious or life-threatening conditions and address an unmet medical need.
- Potential to Offer an Advantage: The drug must show potential to provide a significant advantage over existing therapies. This could be through improved efficacy, fewer side effects, or better convenience for patients.
So, if in the early studies, the Cynata competing product shows either greater efficacy, has fewer side effects, or if it offers better convenience for patients, Cynata could apply for Fast Track Designation. That will help.
IN CONCLUSION (and my point is): I do not think people should be overly concerned about what Mesoblast do with regards to a Ryoncil label extension, as it does not necessarily mean the end for a Cynata product, especially if the Cynata product is better (as is being argued by many)! First in Class can be displaced by Best in Class!
CONFLICT OF INTEREST: I hold both MSB and CYP, and I am currently in an investor
equipoise (if such exists)!
Thank you all for sharing what you have shared. I learn a lot from reading your offerings - including the heated debates!
GLTAH!primary endpoints for either the steroid-refractory (35% vs. 30%, n=260) or theirst-line (45% vs. 46%, n=192) GvHD trials.* The primary endpoint for the steroid-refractory GvHD trial (durable complete response) for the per-protocol population approached statistical significance (40% vs. 28%, p=0.087, n=179).
(20min delay)