In an unprecedented move, GBR’s (United Kingdom) NICE (National Institute for Health and Care Excellence) recently recommended NHS (National Health Services) funding of $GSK’s gene therapy STRIMVELIS™ for an ultra-orphan immunodeficiency disorder ADA-SCID1 – also dubbed the “Bubble Baby Syndrome” – at EUR 594,000 (ex-VAT2 price, about USD 700,000). Importantly, this amount does not consider the travel and hospitalisation costs that the NHS must also fund, as the specialised treatment can only be administered in Milan. Given NICE’s resistance to such high per-patient therapy costs, how was $GSK able to defend the value positioning of the STRIMVELIS™ to NICE?
According to the EMA, there are approximately 2,000 people in the EU affected by ADA-SCID. With around three ‘bubble babies’ born in GBR each year, STRIMVELIS™ fits the criteria to be evaluated by NICE’s ‘very rare’ conditions review pathway – the Highly Specialised Technology (HST) track. However, history (specifically the commercially challenged GLYBERA™ (alipogene tiparvovec, $QURE)) indicates that being orphan or ultra-orphan doesn’t necessarily guarantee a NICE HST nod for sufficiently high enough pricing and access to justify the commercial model necessary for gene therapy. In fact, NICE’s backing of STRIMVELIS™ represents the first time that the HST’s GBP 100,000 cost-effectiveness ceiling for rare diseases has been applied since the threshold’s introduction in April 2017.
The key to $GSK’s STRIMVELIS™ triumph through NICE’s HST is the clear story the company was able to tell about unmet need, the critical role the therapy would play for an ultra-rare condition, and the common-sense economic story that results (FIGURE 1). Up to 80% of ‘bubble babies’ don’t have suitable matched stem cell donor and must resort to less preferred, alternative stem cell treatments, which can result in mortality rates as high as 59%. With this devastating unmet need in mind, STRIMVELIS™’s clinical trials boast a 100% survival rate, with a post-treatment, intervention-free survival rate of 82%. According to NICE, the gene therapy has demonstrated almost 14 incremental quality-adjusted life-years (QALYs) over the standard of care. Notably, QALYs arising from STRIMVELIS™’s long-term survival benefit accounted for 83% of the total QALYs attained. The clinical need for access by these patients to the therapy is clear to even the most sceptical payer.
FIGURE 1. STRIMVELIS™ Value Positioning for GBR’s HST Pathway
While NICE identified other value drivers in their QALY analysis, such as one-off QALY loss due to acute graft versus host disease, ultimately, mortality benefit, rather than health-related quality of life improvements, was the true driver of STRIMVELIS™’s almost 14 QALY gain over the standard of care. Based on the clinical evidence, NICE determined that the EUR 594,000 STRIMVELIS™ falls significantly below the GBP 100,000-per-QALY-gained threshold. In the context of HST – as well as most QALY-based cost-effectiveness systems – STRIMVELIS™ is worth the list-price-based, one-time NHS cost.
What does STRIMVELIS™’s NICE reimbursement success mean for orphan drug manufacturers?
Given overall affordability challenges and the increasingly-crowded rare disease space, non-oncology orphan-disease therapy manufacturers must work to effectively frame the value of the therapy based on patient flow, unmet need, , and the evolving policy environment that contextualise traditional value drivers. Doing so can lead to a greater appreciation of the value of therapy – even at prices that may cause initial concern. Next generation therapies often require bespoke tactics to mitigate likely payer objections, such as the affordability of one-time treatments and uncertainty associated with long-term clinical and economic value. A robust, yet complicated evidence foundation does not spell automatic access – and such evidence must be formulated to support simple, undeniable messages for patients, caregivers, physicians, and payers. Understanding how manufacturers of other brands have failed (and succeeded) can make the difference between history repeating and the awakening of payers to the sensibility of providing access at a commercially-sustainable price. $GSK was wise to learn from $QURE’s experiences, and have no only succeeded in bringing a vital therapy to a rare, but vulnerable patient population – they have also done so in a way that they can commercially support the availability of the therapy while reinvesting in other life-saving therapy.
$GSK’s success with STRIMVELIS™ can be replicated, but as $QURE can attest, an innovative mechanism of action alone is not sufficient. STRIMVELIS™ may have paved a path forward for gene therapy market access in GBR; however, it remains to be seen if manufacturers of other innovative gene therapies can successfully follow in $GSK’s footsteps by learning from them and other manufacturers pursuing the HST pathway.
The STRIMVELIS™ case is an extreme one – the patient size is about as small as they come, the unmet need among these patients is obvious and drastic, the new therapy allows young patients to live many years longer. However, such an extreme case allows for close examination of what it takes to achieve access in the new world of orphan disease therapy value assessment – both in GBR and beyond. Very few other orphan disease therapies will be able to approach NICE’s HST pathway with as convincing evidence. However, $GSK’s positioning of STRIMVELIS™ may be viewed as starting point from which other manufacturers can work backwards in order for their new products to gain access at a commercially sustainable price.
- ADA-SCID = Adenosine Deaminase-Severe Combined Immunodeficiency;
- ex-VAT = excluding Value Added Tax