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Whither mRNA? [Muldoon]

Over the past two years people have been exposed to vast amounts of published information about mRNA in the context of COVID vaccine development. But the story goes deeper and further into the future than just COVID.

Without getting too far into the weeds, basically mRNA technology involves inserting the messenger RNA code for a specific protein into an envelope such as a lipid nanoparticle soft shell, injecting that into a patient's muscle where it is taken into muscle cells and lymphocytes and used by those cells to manufacture the desired protein for use by the body. This can involve a direct action by that protein (e.g. to replace a critical protein that may be missing as in a genetic deficiency of some sort). Or, the protein could have an indirect effect, interacting with the patient's immune system to provoke a protective immune response, such as in vaccination or potential cancer immunotherapy.

The first mRNA therapeutic approved by the FDA was for a condition known as hereditary transthyretin-mediated amyloidosis, a rare genetic disorder that causes neuropathy, all the way back in the dim mists of the past, circa 2018.

mRNA technology has been proposed as potentially useful for a wide range of clinical uses, including vaccinations, antibiotics, antivirals, cancer, autoimmune diseases, and rare genetic defects

Genetic deficiencies represent a small niche market (due to the rareness of these diseases ) but do function as a humanitarian fig leaf of sorts (a loss leader) for pharmaceutical companies to help prop up larger scale usages that do have a more substantial profit potential.

Pfizer states they are "committed to treating 225M people with breakthrough treatments by 2025." Some of these will be mRNA based therapeutics. For example, Pfizer has an mRNA based influenza vaccine currently in Phase 1 trials (PF-07252220). The potential applications for mRNA therapeutics are numerous and potentially involve large groups of patients and therefore are likely to be lucrative. As Joe Biden might say, "This is a big (expletive) deal!"

Pharmaceutical companies play it close to the vest regarding products in the pipeline, particularly regarding the delivery mechanism (lipid nanoparticles et al.). The various players in the mRNA technology field are prepping the battle space for proprietary rights and scrambling to position themselves for a vast new market.

As expressed by patent lawyer Dan Shores in April 2021 in The mRNA Patent and Competitive Landscape, regarding proprietary rights, patent infringement and licensing of technical processes:

"Expect to see more strategic validity challenges to be filed as the commercial mRNA markets develop, especially since invalidity proceedings like IPRs are relatively inexpensive to pursue (e.g., estimated hundreds of thousands of dollars vs. district court litigations which could cost millions of dollars), while potentially yielding huge upside with respect to freedom to operate, depending on the markets involved."

In a sense, the development of the Pfizer/BIONTech and the Moderna/AstraZeneca mRNA COVID vaccines was a boon to those companies beyond any immediate financial gain. The stated medical imperative of the pandemic led to fast tracking of the regulatory process due to the stated emergency nature of COVID. In terms of future drug development, this also acted as a "proof of concept" to help speed FDA approval of future products that use the same technology.

From Pfizer's Chief Development Officer and Executive VP Rod Mackenzie in September 2020. Other diseases deserve the same [regulatory] acceleration as COVID-19

Hence, Mackenzie, in shifting from a medical imperative to a moral imperative to justify fast tracking virtually all new meds, comes pretty close to echoing "never let a crisis go to waste." He added that the level of preparedness needed to successfully carry out a rapid pharmaceutical response to a future medical crisis is a ...

...very expensive proposition that requires a huge commitment of governments, particularly, because they will be the ones to coordinate all this and then ultimately taxpayers would have to fund it.[emphasis added]

There is no doubt that mRNA technology, while promising, remains in its infancy. Will it lead to major breakthroughs in disease treatment or will its promise remain unfulfilled? While justifiable criticism has been directed at the FDA, for a slow, costly and complicated approval process, prudence would dictate a measured approach for an emerging technology rather than a "full speed ahead" philosophy, especially when the entities advocating for fast-tracking stand to reap tremendous profits. The regulatory state and mega pharmaceutical companies make for an odd and potentially dangerous marriage, with the implication that taxpayers may be on the hook financially and individual patients may pay a price medically in the event of unforeseen late sequelae. This question must be asked: Do Pfizer and Moderna have a financial incentive to downplay (or even perhaps seek to censor) reports of adverse effects while simultaneously talking up the efficacy of their vaccines? The answer seems apparent, and the ramifications go well beyond COVID-19.