RCDP Program Update
Hello RCDP community. There are several updates about the program we wanted to relay to everyone, so apologies in advance for the lengthy post!
First a huge thanks to everyone continuing to participate in the Natural History Trial. This month we will officially be exporting some of the data to analyze for endpoints we will use in the intervention study. To date we have been “unofficially” looking at the data, and what has emerged is the criticalness of longitudinal visits. We are sure you already knew this, but RCDP children vary a lot when it comes to the assessments we have collected, however, these datapoints don’t change as much when we consider the same child over time. So, having these trajectories could be important when it is time to evaluate effectiveness of the plasmalogen therapy. For anyone who has just one visit, we would really encourage you to try to make it back for at least one more, as we need at least two (but ideally three) visits to include your child in a longitudinal dataset. However, more is always better, so even if you have completed three or more visits, we encourage you to keep visiting as long as the study is on-going.
Second, we are excited to announce we have officially completed all of the preclinical safety and toxicity animal studies, with the final reports showing the drug is safe and well-tolerated at doses anticipated being used in RCDP patients. Recall these are FDA-required studies that are non-negotiable when developing any therapeutic (more on this later!). Completing these studies is also required before the FDA or Health Canada will let us (or anyone developing a therapy) put the drug into a human for the first time. This brings us to one of the most exciting parts of our update, that is, the Phase I clinical trial.
Third, we are finally gearing up for the first in human Phase I clinical trial, and our investors have committed another round of several million dollars into our RCDP program to get this trial going. This Phase I trial, as requested by the FDA, will be a healthy adult study. The reason the FDA recommended this was because we are developing a novel plasmalogen drug that is a true “first in class” therapy that has never been tested, and the FDA (along with Dr. Bober and the rest of the clinical team) all agreed that safety of the children is the number one priority. Therefore, performing a traditional Phase I in adults in a controlled environment is in the best safety interest of everyone. The other reason the FDA requested a Phase I in adults was that if we used RCDP children in a Phase I, they would become ineligible for the therapeutic intervention trial that assesses the drug’s efficacy, limiting the number of potential patients even further.
Currently Tara has been working with our Phase I site (in Toronto) to finalize the study design, which is planned to begin enrollment between the end of this year and early next year. We also have another PreIND meeting set with the FDA next month for clarification on several key points including drug manufacturing, Phase I design, the therapeutic intervention study, and use of plasmalogen measurements for accelerated approval. This last point is of particular importance and the reason why we have “plasmalogen supplements” as exclusion criteria in the Natural History Trial. Because we know baseline plasmalogen levels in RCDP correlate with disease severity, we can make a strong case that the safe augmentation of plasmalogens should improve some clinical outcomes. A person taking a plasmalogen supplement “might” cause a skewed result if the supplement actually did anything, which would negate the purpose of the whole study. This is anticipated to also be an exclusion criteria in the future intervention trial, which is necessary to ensure good quality data (as described above) and to ensure the safety of participants as it would be impossible to know how the body would react to combining supplements and our drug product.
This leads us into the fourth point about plasmalogen supplements themselves. We are obviously aware that there is an ever-growing list of manufacturers with a slew of unproven claims about their plasmalogen products. Many of these we have purchased and tested in our accredited labs at MLD, and most of them contain only trace amounts of plasmalogen mixtures along with other non-plasmalogen lipids and other contaminants. None of these products to our knowledge have undergone the required safety testing that should be performed before being used in humans – especially at concentrations higher than what are found in dietary sources (which are in the microgram range and thousands of times lower than what our drug will be dosed at).
As parents of young kids ourselves at MLD, we know that there can be motivation to do anything possible to help your child. We get it, and ultimately it is each parent’s choice to do what they feel is in their child’s best interest. However, I would caution anyone entertaining the idea of trying any of the over the shelf plasmalogen products to do some research on the product first. Who is making the supplement, and do they have a proven track record for making commercial supplements? Was it performed in an FDA-audited GMP manufacturing facility (Good Manufacturing Practise; a high standard required for facilities that make drugs)? Was it an extract of something, or made synthetically from scratch? If it was extracted, are all the chemicals used in the process actually removed from the final product? What other “junk” came along during the process? Are these impurities reported and characterized? If it was made from scratch in a chemistry lab, what were the starting materials? Were they GMP grade and tested prior to use? What other chemicals and solvents were used in the synthesis and purification? Were they toxic or carcinogenic, and if so, were they removed from the final product? How was this confirmed? What about stability? Does the molecule break down into other things? Have formal GMP stability studies been completed at different conditions? Then there is the safety. Has the product been adequately tested in animal GLP safety tox studies? If the claimed dose is higher than what is found in nature, has there been formal Phase I safety data generated, including bloodwork, ECGs, in-patient monitoring, etc.? These are only a few of the critical questions and efforts that go into the development of any legitimate drug, and that should also go into the development of high-dose natural products, although it is not formally regulated for the latter.
We know it has been a long road to get to this point, and we appreciate your patience as we do this the right way. We can see a future where late in 2023 we are gearing up for the full intervention study phase of the program! Next month we plan on hosting one or more virtual RCDP zoom sessions where we will give more updates on the program, provide opportunities questions, and get feedback on the Natural History Trial logistics to date. It will also be an opportunity to ask any questions about this post or anything relating to our entire program. Also, if one day you notice parts of the RhizoTrial.org website down, don’t worry, it’s just us updating some content!
Lastly but not least, a huge thank-you to Dr. Bober and his team at Nemours. We plan to be back in Delaware at the end of September to review more Natural History Trial data and continue auditing records to ensure the data meets FDA quality standards in terms of rigor.
Take care and we look forward to meeting new families and catching up with others we know virtually in the near future.
Sincerely,
The MLD team.