The MIT Technology Review article cited in the question gets the current data about UniQure and its Gene Therapy (GT) product, Glybera, right. However, lacking historical context, its analysis is short-sighted and fails to hold the spotlight on the main culprit, namely a doddering healthcare financing system firmly stuck in the past and highly resistant to innovation.
1999-2004: Excess Hype Followed Closely By Tragedy Made Gene Therapy (GT) A Scientific Outcast For Several Years
Eliciting stratospheric levels of interest and enthusiasm, GT was an undoubted star of the 1990s biotech firmament. Early results heralded a new era of potential cures for hitherto incurable diseases like hemophilia. However, its promise came to an abrupt, screeching halt. Reason? Two sequential human GT tragedies,‘s death in 1999 during a GT trial in Philadelphia, USA (1, 2), and in 2004, leukemia in 3 of 11 GT-treated severe combined immunodeficiency (SCID-XI) children in France directly as a result of the gene transfer (3) (see figure below from ). Seemingly in an instant, GT became a scientific outcast. Its funding dried up. Following capital’s flight, scientists quit the field in droves. Making GT palatable again entailed two dauntingly uphill challenges for its remaining die-hard enthusiasts, to prove it was safe enough for a 2nd chance and carefully plot a path to regulatory approval now rendered even more onerous.
2000s till date: Now the Underdog, GT Makes A Quiet, Steady But Undeniably Noticeable Comeback
Slowly over the course of the 2000s, these die-hard GT specialists built up an impressive portfolio of promising clinical trial results for a variety of chronic diseases such as Leber congenital amaurosis (LCA), an inherited recessive blindness (, , , ), Lipoprotein lipase deficiency (LPLD), a rare autosomal recessive disorder Uniqure’s Glybera promises to treat better than current options, if not cure ( , , ), and more prevalent diseases such as Hemophilia ( , , , ), Parkinson’s ( , 17, ).
Into this mix came small intrepid biotechs like UniQure. Knowing the path to regulatory approval for GT was now steeper, they cannily focused on an inherited metabolic disorder that affects a relatively tiny proportion of the population. Let’s consider such diseases for a bit. Relatively small population bases make them unattractive research topics in both pharma and academia. In essence, people with such diseases are captive patients. Lacking strength in numbers, they can’t dictate terms. No option but to submit to the sparse disease management options available. Classic scarcity of Rx. Along comes a company with a potential cure and what else could it be but manna from heaven? Similar calculation at play for the regulators. Potential cure for a small group of patients whose current disease management options are far from optimal implies benefits easily outweigh the risks. Hence lower bar for approval. This is likely how UniQure estimated Glybera’s cost-benefit and how it seems to have indeed panned out. Seen from this perspective, Glybera is anything but a failure and its company, UniQure, anything but short-sighted for focusing on LPLD as a path to pioneer regulatory approval for GT.
The spotlight then turns logically to how to pay for such Rx. Crux of the problem is current healthcare financing models. Too single-mindedly focused on short-term bottom-lines, they remain almost completely unprepared to meaningfully incorporate payment plans for potential cures for chronic conditions (). Meantime, technology is accelerating the potential for future spectacular Rx successes but alas, healthcare systems prevailing today lag far behind in appreciating and accommodating this new normal, namely, cure when the only previous options were incremental improvements or lifelong management. This applies not just to GT but also novel immunotherapies like those for cancer, and newer drugs that could potentially cure other previously chronic conditions. Such a status quo leaves in the lurch millions of patients whose conditions are now potentially curable. Left stranded like thirsty desert wanderers of yore who mistook distant shimmering sand particles for oases. Only in this case, their visions are no mirages, making their predicament all the more palpably egregious and acute because this is an eminently solvable problem but for pricing and accounting systems stuck in old ways.
Currently a lifelong chronic condition, GT could cure hemophilia in the near future for example. Cure! An entirely different ball game to what current healthcare financing models accommodate. Strictly short-term in vision and approach, healthcare financing typically factors costs of chronic conditions piece-meal. Estimated to cost US $300,000 per year per patient (), weekly prophylactic clotting factor Rx is only one cost for managing hemophilia. Such prohibitive costs render hemophilia prophylaxis out of reach even in wealthy countries. The norm is instead on-demand (episodic) Rx (20), classic rationing of care. Such sub-optimal management only increases hemophilia’s other lifelong risks. Hospitalizations, joint damage, viral infections from transfusions (screenings minimize but don’t completely eliminate) to name just a few. What about their lifelong economic costs? Estimated separately of course. No surprise then that such a system would balk at a one-time bolus cost for potential cures of such chronic conditions. It’s simply not set up to consider, let alone estimate, cumulative costs. Just consider for a minute all the lifetime healthcare resources, personnel and time it takes to manage a single hemophiliac in an advanced economy today. With GT, all those cumulative burdens could potentially be eliminated in one fell swoop.
Nor does the prevailing healthcare pricing system seem capable of parsing accounting for diseases with smaller (LPLD) versus larger (hemophilia) population bases (see figures below from). Given stark differences in population size, associated complications and risks, healthcare pricing plans even for simple genetic diseases simply cannot be one size fits all.
Thus major structural problems in current healthcare financing are serious obstacles in funding Rx like GT that could potentially cure diseases that until now were managed as lifelong conditions. How then to pay for such potential cures? Unfortunately, solution is obviously not in the hands of hapless patients but in those of lawmakers, regulators, insurers, Rx developers and their funders who need to evolve healthcare pricing structures fundamentally different from those that existed before (, ). Hence it’s unfair to pin the blame solely on UniQure for how Glybera panned out. As far as the GT field is concerned, UniQure has done the necessary needful. Given the debacles of the 1990s, regulatory approval of its Glybera sets a precedent that can only be beneficial for GT’s future. Ultimately, GT’s promise lies in potential cures for single gene defects. At >2000 diseases and counting, GT’s potential to cure human genetic disease is by no means a humble goal. If it fulfills this goal even partially, imagine the release from pain and suffering for the millions directly and indirectly affected. Incalculable.
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