Every modern PNH anti-complement therapy has cleared NICE's standard £20,000-30,000 Technology Appraisal route via a confidential commercial arrangement, and crovalimab's most recent approval turned on a cost comparison against the incumbents, so a new entrant's HTA strategy must be built for the standard threshold and an established class comparator set, not the Highly Specialised Technologies band.
NICE runs two appraisal tracks for ultra-rare conditions: the standard Technology Appraisal, which applies a £20,000 to £30,000 per QALY threshold, and the Highly Specialised Technologies route, reserved for the very rarest conditions and applying a far higher threshold. PNH sits close to the prevalence boundary, yet NICE has routed every modern anti-complement therapy through the standard track. Ravulizumab was recommended under TA698 in May 2021, pegcetacoplan under TA778 in March 2022 for residual anaemia after a C5 inhibitor, iptacopan under TA1000 in 2024 as NICE's 1,000th published appraisal, and crovalimab under TA1019 in November 2024. Each recommendation was contingent on a confidential commercial arrangement rather than a lower list price. Eculizumab, the original C5 inhibitor, predates these appraisals and was commissioned directly by NHS England as a highly specialised service, not through a numbered NICE technology appraisal.
That unbroken record is the strategic problem a new submission must solve. The bar is the ordinary £20,000 to £30,000 threshold, roughly a tenth as forgiving as the HST band, and four consecutive approvals have now cleared it through confidential discounting rather than modest list pricing. Crovalimab's TA1019 raised the difficulty further by winning on a cost comparison against ravulizumab and eculizumab, which signals that NICE will accept, and increasingly expect, a non-inferiority-plus-lower-cost case in this class. A new entrant therefore has to fix its PICO around the established anti-complement comparator set, decide early between a cost-comparison and a full cost-utility submission, and size the confidential discount needed to clear the standard threshold before the dossier is drafted. Our gap register scores each of those decisions against the four-appraisal precedent, not against an HST eligibility the class has never been granted.
UK PNH NICE appraisal precedent — four standard Technology Appraisals, no HST, each on a confidential arrangement
| Agent | NICE TA | Appraisal Route & Outcome | Precedent for a New Entrant |
|---|---|---|---|
| Ravulizumab (Ultomiris) | TA698 | Standard STA, recommended May 2021 with confidential PAS | Standard £20K-30K threshold; the entrenched anti-C5 comparator |
| Pegcetacoplan (Aspaveli) | TA778 | Standard STA, recommended March 2022 for residual anaemia after a C5 inhibitor | Standard threshold; sets the residual-anaemia comparator |
| Iptacopan (Fabhalta) | TA1000 | Standard STA, recommended 2024 (NICE's 1,000th appraisal), confidential arrangement | Standard threshold; the oral Factor B comparator |
| Crovalimab (Piasky) | TA1019 | Standard STA, recommended Nov 2024 on a cost comparison vs eculizumab and ravulizumab, simple-discount PAS | Signals NICE will accept a cost-comparison case in this class |
| Eculizumab (Soliris) | None (pre-appraisal) | NHS England highly specialised commissioning | Original C5 inhibitor; not a numbered NICE appraisal |
Sources: NICE TA698 (ravulizumab, 2021); NICE TA778 (pegcetacoplan, 2022); NICE TA1000 (iptacopan, 2024); NICE TA1019 (crovalimab, November 2024); NHS England Highly Specialised Services specification for PNH.
What this model answers
Every section answers a named commercial question your team is asking, scoped to your asset.
Delivers
- The prevalence and precedent logic behind four consecutive standard-STA recommendations (TA698, TA778, TA1000, TA1019)
- why the £20,000-30,000 threshold, not the HST band, is the fixed bar
- and the anti-complement comparator set a new PICO must be built around
Delivers
- The decision logic between a cost-comparison and a cost-utility submission in this class, tested against the TA1019 precedent and the value-dossier self-assessment, and what each route demands of the economic model
Delivers
- PAS discount depth benchmarked to the incumbent confidential arrangements, the NICE pre-submission scoping and MHRA ILAP timing (roughly 24 months pre-approval), and the Leeds National PNH Registry real-world evidence that strengthens the dossier
Custom model delivered in 72 hours.
Commission This ModelWhat's inside
- Why the unbroken standard Technology Appraisal precedent, not the HST band, is what a new submission must be built to clear first
- Pressure-tested against the TA698, TA778, TA1000 and TA1019 record before the rest of the model is built out
- NICE's standard Technology Appraisal process and why all four PNH anti-complement approvals used it rather than the Highly Specialised Technologies route
- How NHS England Highly Specialised Services commissions the class, and what that adds to a numbered NICE appraisal
- Population, Intervention, Comparator and Outcomes built around the established anti-complement comparator set
- Framing the broad haemolytic-anaemia population against the 200-250 patient EVH-dominant residual-anaemia cohort from the Leeds National PNH Registry
- The 3-test comparator defence applied to a new C5 or Factor B entrant against ravulizumab and iptacopan
- What crovalimab's TA1019 cost-comparison win signals about the comparator case NICE now expects in this class
- 5-module, 15-check self-assessment against submission readiness
- Testing the dossier against the cost-comparison and confidential-PAS precedent the four incumbents have set
- Utility and quality-of-life, transfusion-offset and EVH-sizing evidence gaps scored by likelihood of challenge and impact
- Submission-blocking versus manageable classification for each gap
- Choosing between a cost-comparison and a cost-utility model, and the PAS discount depth (roughly 30-40% off a UK price near £250,000 per year) needed to clear the standard threshold
- Milestone timeline incorporating NICE pre-submission scoping and an MHRA ILAP filing roughly 24 months ahead of approval, with Leeds National PNH Registry real-world evidence
- The open HEOR and stakeholder-engagement questions your team must close before the dossier is finalised
Included with every brief
How AXLRx builds this model
Prepared by MoatRx analysts.
Every AXLRx HTA strategy model is built from primary HTA-body sources: NICE technology appraisals and final guidance documents, not secondary summaries. Every comparator and threshold claim is pressure-tested against the live appraisal record before it is accepted.
UK PNH HTA sources: NICE TA698 (ravulizumab), TA778 (pegcetacoplan), TA1000 (iptacopan) and TA1019 (crovalimab), plus the NHS England Highly Specialised Services specification for PNH. Each appraisal was checked to confirm the standard Technology Appraisal route and the £20,000-30,000 threshold, not the Highly Specialised Technologies band.
- Ravulizumab TA698, pegcetacoplan TA778, iptacopan TA1000 and crovalimab TA1019 each confirmed as standard single technology appraisals against live NICE guidance
- Crovalimab's TA1019 cost-comparison basis and simple-discount patient access scheme verified against the live NICE recommendation
- Population figures (roughly 1,500 diagnosed, roughly 600 on complement inhibition, 200-250 EVH-dominant) verified against AXLRx's UK PNH launch-readiness research and the Leeds National PNH Registry
Frequently asked questions
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AXLRx delivers rare-disease HTA strategy models built for market access and HEOR teams navigating NICE's standard Technology Appraisal precedent and confidential-arrangement dynamics. Custom model in 72 hours.
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