MAHA Vows to Disrupt Sick-Care Model in Favor of Cures

There is now overwhelming evidence that the new US healthcare administration is serious in its mission of making its citizens inherently healthier by putting more emphasis on disease prevention and actual cures to move away from the current sick-care system of chronically medicating sick people.  Importantly, CMS Administrator Dr. Oz who wields outsized influence on how healthcare dollars are spent is working on adjusting financial incentives to make developing cures a viable business model.

False alarm

When RFK Jr was appointed HHS Secretary under Donald Trump, alarm bells went off in the healthcare industry driven by a  concern that this could spell the end of evidence-based medicine.  This was largely because of his natural bent towards seeing conspiracies and skepticism of the pharmaceutical industry that became radicalized following some government overreaches during Covid19.  Although proposed 40% NIH budget cuts could turn out to be an instance of unfortunate politicization of health research, concerns scientific evidence will be generally replaced with arbitrary political views as the guiding principle in shaping healthcare turn out to be misplaced.  This is due in large part of RFK having surrounded himself with well-intentioned people of reason who want to better the health of the American people and beyond.

This could also be genome editing’s moment.

FDA cell and gene therapy roundtable

There has never been a more transparent FDA.  Even the politically charged waters of Covid19 vaccine regulation were elegantly navigated through communication and eventually approving vaccines from both Novavax (protein) and Moderna (mRNA) with some limitations as to who can access it and a randomized trial obligation for Moderna’s novel bipartite mRNA design.  Who knows, at the end of this, confidence and use of vaccines may actually increase with this slightly more restrictive stance as opposed to their rapid decline under a much looser regulatory regime before.

The transparency drive is paired with listening to patients, physicians, scientists, and industry to inform their initiatives.  Last week’s cell and gene therapy session organized by Vinay Prasad’s CBER was a major event in that regard and offered the intriguing insight that genome editing is shaping up to be exemplary of what MAHA movement wants to achieve.

CRISPR lovefest

The event was attended by those wielding major power in the US healthcare and drug development system, with HHS Secretary Kennedy, CMS Administrator Dr. Oz, NIH Director Bhattacharya, FDA commissioner Makary and CBER chief Prasad all in attendance.  The speaker line-up featuring widely respected top scientists and patient advocates underlined that this event was not abusive political theater, but directed at making true progress in healthcare.

The CRISPR base editing for the child with a rare urea cycle disorder became the posterchild of how the new FDA wants to facilitate speedy, patient-oriented, common sense drug development- in this case, as the child is now at home, arguably a cure at that.  It is based on having a plausible mechanism, general platform knowledge (LNP-mRNA CRISPR for the liver), and the right to try.  Top genome editing scientists Dr. Liu and Dr. Urnov highlighted that other CRISPR therapeutics, including first curative prime editing in humans, have showcased the transformational nature of this technology. 

Daily pills not a panacea

Like many who try to live a healthy life by eating well and exercising- whatever this may mean to them-, RFK Jr looks at pills as toxic chemical compounds, placed next to oil-based food colorings on the chemical shelf.  I hope that this view will be mollified as he, as the head of HHS, will inevitably learn more about modern drug development and regulation and the people who conduct it. 

We also know that such views can have tragic consequences for example when a person that is at high risk of stroke does not take blood thinners and eats blood-thinning food instead or when a person insists on beating an aggressive cancer by healthy living alone.

In any case, taking daily pills for him is to keep patients sick and a recurring revenue opportunity for pharmaceutical companies.  According to RFK, they did not exist in the 60s and are now pervasive and keep people ‘barely functional’.

To be clear, I like a ‘daily pill’ if there are no good alternatives, but as we know from the cardiovascular and ocular disease space as examples, this can be not only burdensome financially, strain healthcare resources and impact quality of life (e.g. monthly intraocular injections), and still lead to suboptimal outcomes as many patients ultimately fail to adhere to their treatments.

Righting incentives in favor of cures

So why on earth have investors steered clear of genome editing and gene therapy despite of these technologies having resulted in the major recent pharmaceutical breakthroughs (urea cycle base editing, Intellia’s emerging NTLA-2001 long-term ATTR outcomes, prime editing cures for CGD, Beam Therapeutics’ base editing for AATD)?  The insanity has degenerated to the point where on platforms like X it has become the mainstream believe among biotech influencers that taking daily pills was preferable to actually curing people and preventing disease when there is a choice.

And why is it even a discussion if paying $2M for a life-time cure is more expensive than spending $200,000-500,000 annually for decades?

Take for example hereditary angioedema where the current best treatment paradigm involves start taking the highly effective and well tolerated drugs in the 20s until basically the end of life.  While a godsent compared to old ineffective treatments that came with a high side effect burden und moderate efficacy, the fact that this orphan disease of maybe 10000 patients in the US and Europe is attracting a dozen or so drug developers is due to these treatments commanding around $500,000 annually.  So when an equally effective and safe one-time CRISPR treatment in the form of NTLA-2002 by Intellia Therapeutics comes to market, the $2.5M price that I project it will cost should amortize very quickly and pulverize the HAE prophylactic drug market.  Let alone the quality of life benefit of essentially curing a good fraction of patients and letting them forget about their disease, including not having to worry about drug access in an increasingly uncertain world  (longer-term data for NTLA-2002 coming up in a week).

The billions saved annually through this marketplace disruption could be spent on other innovative treatments for other diseases.

Or take VERVE-102 as an example of using genome editing for disease prevention.  I expect this one-time medicine to initially cost around $100,000 in return for essentially eliminating the risk of dying or being sick due to LDL-cholesterol driven cardiovascular disease.  As I grow older (48 years) I am increasingly aware that my LDLc of 150mg/dL means that heart attack or stroke are my most likely causes of death and that over the next 5-10 years I need to get real serious about addressing it, ideally in the form of a one-time PCSK9 gene edit and then get on with life.  This assumes that VERVE-102’s acute liver safety profile is holding up.

The frequently hostile and belittling views of gene therapies and genome editing can be explained by the many perverse incentives of healthcare systems where physicians and hospitals make money from buy-and-bill medicines that are regularly administered in the office, co-pay systems that depend on who, how, and where a drug is administered, and where insurers and PBMs make money from a convoluted maze of discounts, drug bundling and who knows what other tactics.  And following the healthcare situation in Germany, politicians could not care less about cost implications beyond their 4-year terms. 

CMS Administrator suggests socialization of costs

At the end of the day, CMS Administrator Dr Oz agrees that it is unacceptable to deny $2M for a CRISPR genome editing cure for sickle cell disease when $4 trillion are being spent annually in the US healthcare system.  Insurance companies and PBMs partly hinder access because they can only think out 1-2 years into the future instead of considering the overall healthcare benefits.

Dr. Oz suggested at the roundtable that in this situation a reinsurance scheme could be the solution as it would socialize and thus buffer the unevenly distributed, chunky payments for one-time therapeutics.  This strikes me as one of the best solutions to this problem I have heard of and falls short of introducing a single payor system.  It may be combined with a pay-for-performance model where there are rebates for non-responsive patients or where payment is staggered over a period of time and tied to continued treatment response.  The latter could be useful when there is concern that for example expression levels following AAV gene therapy are not sustained (e.g. in hemophilia).

It is encouraging to see concrete solutions being developed so that gene therapies and genome editing can be viewed as attractive investment opportunities.  Importantly, Dr Prasad noted that not only cures will be rewarded, but, especially for severe, rare diseases of high unmet medical needs, also steps in the right direction.  After all, without investments the new FDA has little to brag about in its mission to turn the current sick-care paradigm into one focused on disease prevention and cures.  Personally, I believe having new, well-intentioned leadership may have been the missing necessary catalyst to finally realize the 21st century cures era.