An Urgent Public Call For Support From Michael Milken and The Milken Institute: Treatment of COVID-19 Disease Using CYCLOSPORINE.
Mr. Milken and colleagues at the Milken Institute,
I am writing this public letter to you with urgency in order to bring your team’s attention to the generic drug, CYCLOSPORINE, vis-a-vis the COVID-19 pandemic.
I ask that you please read my several analyses about CYCLOSPORINE HERE, HERE, and HERE.
Please also watch THIS news clip from CBS Los Angeles with care.
Along with a group of colleagues, on March 26, 2020, I submitted what we believed to be a scientifically and clinically well-reasoned “Emergency Use Authorization” (EUA) application to FDA’s Center for Drug Evaluation and Research (CDER). In this application, we proposed to test CYCLOSPORINE for blockade of COVID-19 disease progression to critical illness using a “Real World Data and Evidence” mechanism.
One month later, on April 27, 2020 FDA rejected this EUA application. This rejection was because CDER, unlike other Centers within FDA, will not efficiently utilize “Real World Data and Evidence” Collection, as was legislated into law in the 21st Century Cures Act of 2016, for drugs.
This was a surprising decision by FDA given how well-established and safe CYCLOSPORINE is as a generic drug — and given the fact that there is a vast clinical experience with this drug’s ability to dampen hyperimmune disease flares and “cytokine storm” syndromes of which COVID-19 disease is reminiscent.
The agency instead instructed us to undertake a traditional approach using an IND followed by Phase 1 and Phase 2 trials of this well-known drug. This unfortunately slow process is now underway in parallel. Of course, time will tell whether the FDA decision to reject the CYCLOSPORINE EUA from March 2020, early in the pandemic’s strike on the United States, was a critical regulatory error with a cost to many lives. I do believe that this was likely a dangerously inflexible decision by FDA, given the very well established safety and efficacy profile of CYCLOSPORINE — as thousands of Americans are dying every day from SARS-CoV2 infection, and more across the globe.
Nevertheless, at CDER’s instruction, I am privileged to have stimulated a movement towards traditional clinical trials by my colleagues and good friends at two major academic medical center in the United States. These trials are currently in the very early administrative stages of being initiated — with one of the centers, in Philadelphia, poised to initiate a small phase 1 clinical trial later this month.This group is led by Dr. Carl June and friends at the University of Pennsylvania. You may read about Professor June’s evolving focus on CYCLOSPORINE, HERE.
Notwithstanding, as you will know, this traditional process has been and will be exceptionally slow and cumbersome from a bureaucratic, regulatory and funding perspective — with much competition with other “highly innovative”, but unproven, ideas and more robust large-scale financial interests outcompeting the well-established, inexpensive, vastly available and generic CYCLOSPORINE.
Additionally, I will note that I’ve had the privilege of coordinating an unusual effort focused on CYCLOSPORINE, with the largest COVID-19 treatment center in Tehran, Iran. I believe that this effort will be efficient, fruitful and potentially materialize useful data more quickly than in the US. The Iranian critical care team in Tehran is quite advanced and has already initiated trials using Novartis’ Sandimmune (i.e., intravenous CYCLOSPORINE). That group will be collecting data using the “Real-World Data” mechanism as we proposed to FDA in our EUA application of March 2020.
I’ve been aware of the Milken Institute’s critically important focus on public health and medical research for some time now. Of course, most recently I read about the philanthropic work your institute is doing with regards to efficiently discovering a treatment for COVID-19 disease in the Wall Street Journal Opinion piece, “What Would You Risk for a Faster Cure?”.
Therefore, I was compelled to directly communicate with you at the Milken Institute and to specifically seek your public support to highlight our team’s urgent scientific activity focused on CYCLOSPORINE — both in the professional domain and in the public eye. I believe that because CYCLOSPORINE is a well-established, inexpensive and generic drug there are too many unreasonable barriers to its efficient testing and use for treatment of COVID-19 disease in the United States and Europe. I recognize that the gravity the Milken Institute could bring to the careful evaluation of this generic drug will serve to eliminate the unacceptable resistance we have experienced from both administrative and regulatory dimensions — in government, in industry, in academia and in the press.
Simply put, CYCLOSPORINE is a generic drug that will neither make a lot of concentrated money for any particular corporate entity, nor build any high level academic’s careers — this drug is simply too well established and too inexpensive. I know that this is exactly where your Institute’s gravitas will accomplish the unconventional, if you support our activity and highlight CYCLOSPORINE’s scientific and clinical potential to dampened progression of COVID-19 disease.
To summarize, there is good scientific rationale and clinical precedent to hypothesize that this scalable, generic drug with a well-established safety and efficacy profile for treatment of hyperimmune disease flares, can be used to effectively block progression of COVID-19 disease to critical illness — on a global scale.
I ask that you carefully consider the following three mechanistically and clinically cogent reasons:
1) CYCLOSPORINE has a well-established clinical safety and efficacy profile for the treatment and prevention of several common hyperimmune disease flares — including Ulcerative Colitis, Rheumatoid Arthritis, and Plaque Psoriasis to name a few. Literally, million of people across the world are daily using CYCLOSPORINE to ameliorate hyperimmune disease flares related to overt T-cell and Macrophage activation. Additionally, this drug is known to be clinically effective in the treatment of a good proportion of patients with a rare, but paradigmatic, cytokine storm syndrome known as Hemophagocytic lymphohistiocytosis (HLH).
2) CYCLOSPORINE has a known and specific inhibitory effect on Coronavirus replication, because the SARS-CoV-2 virus utilizes the Calcineurin intracellular pathway to replicate.
3) CYCLOSPORINE is an inexpensive, generic, and non-biologic drug that is vastly available and rapidly scaleable, globally.
I will look forward to hearing from you and your colleagues at the Milken Institute, at your most urgent and earliest possible convenience after you’ve had a chance to review the this letter.
Your in friendship and in defense of global health,
Hooman Noorchashm MD, PhD.
E-mail: noorchashm@gmail.com
