"How large is the opportunity and who controls access?"
An incidence-to-eligible funnel built as a live, re-runnable Excel model: 8 sheets, 119 formulas, zero hardcoded cells. Every conversion step sourced, every assumption editable.
Browse PFM →Coverage criteria and the evidence standard. How payers and HTA bodies evaluate access and step-edits.
Browse P&HTA →A 12-sheet pricing architecture built market by market: price ladder, international reference-price basket, value-based ICER, gross-to-net waterfall, launch sequencing, and revenue scenarios — not a single number, a re-runnable model.
Browse PSM →A static, triangulated patient-count model, not a forecast: 5-sheet workbook (Cover, Model, Research Validation, QC, Sensitivity), every input sourced and re-runnable. Sizing answers how many patients exist today; forecasting is a separate question.
Browse MSM →A 9-sheet HTA submission-strategy model: authority landscape, PICO framework, comparator defence, value-dossier self-assessment, HEOR gap register, and submission timeline — built before the dossier is written, not after.
Browse HTA →Incidence-to-eligible NSCLC funnel by cohort with sourced conversion assumptions and a share waterfall.
CMS routes all four approved 1L NSCLC IO agents through Part B buy-and-bill at ASP+6%. But PD-L1 assay requirements split coverage into three distinct biomarker-testing tiers.
Why the orphan-drug exclusion shields anti-C5 agents from IRA negotiation, ICER's 2024 value verdict on iptacopan, and Part B vs Part D routing.
Tafamidis is shielded from IRA negotiation by the orphan-drug exclusion. ICER judged its ~$268K price ~85–95% too high, and acoramidis plus pending generics are the real net-price levers.
US payers gate the five FDA-approved IgAN therapies on biopsy, proteinuria and RAS-blockade step-through. The Filspari REMS, Part D routing and the ICER 2026 assessment set the rest of the access path.
Specialty-tier prior authorization, prophylaxis above $300K/patient/yr, ICER 2018/2021 value-based benchmarks and no-concurrent-acute-agent rules.
ICER priced efgartigimod's value at $18,300–28,400 a year, under half its ~$418,400 launch cost. That gap is hardening into a three-tier FcRn-to-C5 step-edit across US commercial plans.
Gene-therapy access at $2.2–3.1M, the CMS Cell & Gene Therapy Access Model, VOC-freedom endpoints, and the hydroxyurea step-edit.
Zolgensma's $2.125M one-time cost, outcomes-based Medicaid contracts, and Part B vs Part D routing across three SMA modalities.
Sutimlimab (Enjaymo) is a ~$260K+/year Part B IV biologic in a few-thousand-patient population — and not cost-effective at the current price.
Fintepla's list price runs roughly 3x Epidiolex, and payer scrutiny turns on high WAC against a small, severe paediatric population.
IV enzyme replacement buy-and-bill under Part B vs oral SRT under Part D, the CYP2D6 PA gate, and generic miglustat.
Pompe ERT costs near $400,000 a year in Part B, and remains the only major rare-disease ERT category ICER has never reviewed. Pombiliti + Opfolda splits into two simultaneous prior authorisations across Part B and Part D.
A genetic test gates oral migalastat, and IV enzyme replacement sits in Part B. Fabrazyme has no US biosimilar, and the IRA's orphan-drug exclusion shields it from Medicare price negotiation.
Topical-then-biologic step-therapy, JAK black-box PA gates, ICER's dupilumab-aligned and JAK-discount verdicts, and why Dupixent is not IRA-selected.
Why Rezdiffra's $47,400 WAC lands inside ICER's value range, why the IRA reset hits semaglutide first, and how Part D routing shapes MASH access.
Type 2 Diabetes is IRA ground zero: three orals negotiated for 2026, semaglutide at $274 for 2027, and the class price anchor reset.
CMS's coverage-with-evidence-development registry, not IRA negotiation, is the anti-amyloid access gate. ICER's below-value verdict and Part B routing set the rest.
Medicare covers Wegovy only for cardiovascular risk, not obesity alone. The IRA's IPAY 2027 semaglutide price applies across the franchise, and ICER returned a 2025 'high value' verdict.
COPD access is a pharmacy-benefit story: inhalers and biologics run through Medicare Part D and commercial PBMs, not medical coverage. Step edits gate the base, an eosinophil threshold gates the biologic, and the IRA is reshaping both price exposure and negotiation risk.
US access to plaque psoriasis biologics is gated by step therapy and reshaped by two forces landing together. IRA price negotiation on Stelara and Enbrel, and biosimilar erosion of adalimumab and ustekinumab.
The price ceiling for HR+/HER2- oral therapies is now set directly by the government. Palbociclib was selected for Medicare negotiation with a 50% cut, $15,741 to $7,871, effective 2027. Access runs through Part D and commercial prior authorization, and newer targeted agents face biomarker-gated coverage with cost-effectiveness ratios far above accepted thresholds.
The UK Pompe Consortium registry counts roughly 200 confirmed patients. Total estimated prevalence, including the undiagnosed pool, runs 350-450. Within the confirmed, treated population, 30-50 are ADA-positive inadequate responders and 80-120 are on home ventilation.
Total GCC Pompe prevalence runs 400-600, consanguinity-elevated. 200-300 are actively managed on ERT, and NPHC's formulary budget centers on a narrower 80-120 long-term-stable core within that population.
US SMA sizing splits into two live populations, not one number. 8,000-10,000 prevalent patients across Types 1-4, and a separate 500-700-patient Zolgensma-treated cohort now aging into a monitoring window where 15-20% show early motor plateau.
An estimated 8,000-9,000 Americans have HAE, and only 35-40% receive any prophylaxis. That leaves 2,500-4,000 attack-eligible patients never treated, a pool nearly as large as the entire treated population.
A 37-centre national survey confirms 1,152 UK HAE type I/II patients. A top-down 1:32,000 prevalence rate implies roughly 2,000, and the UK HAE Alliance's broader planning estimate runs to 5,000-6,000, of which only 1,500-2,000 are on prophylaxis today.
The UK SMA population is not one number. A ~1,000-patient actively-monitored NHS cohort and a 1,800-2,000-patient total prevalence estimate both appear across UK sources, and the gap between them is the pre-NBS legacy population outside the four specialist networks' active census.
NPHC's KSA-first coverage model sets the de facto GCC access bar for anti-C5 agents. Iptacopan faces a 12-24 month SFDA registration queue before NPHC even evaluates it.
GCC HAE access is structurally two-tier: broad acute coverage, but a prophylaxis bar few clear. Only 30-40% of applicants clear NPHC's individual-case prophylaxis review, and private insurance beats the NPHC pathway on speed.
100,000-200,000 US gMG patients narrow to a 4,000-6,000 on-FcRn-therapy pool, and 1,200-2,100 of them remain inadequately controlled despite treatment.
NICE's accepted cost-effectiveness case for budesonide (TA937, updated by TA1128) rests on a 5–8 year modelled ESRD delay. The same mandatory ACEi/ARB gate applied to sparsentan narrows the UK's eligible IgA nephropathy population from 10,000–15,000 to 3,000–5,000 patients.
6,000-10,000 GCC gMG patients on the epidemiology estimate, of whom 200-300 are refractory and fewer than 50 are currently on biologic therapy.
GCC tafamidis costs roughly a tenth of its US price, yet uptake is not limited by affordability. Tc-PYP scintigraphy access at fewer than 8 GCC centres is the real constraint.
Newborn screening has been universal since 1999, so the UK's 15,000-17,000 diagnosed sickle cell patients are counted with confidence. They narrow to a 4,000-6,000-patient conventional-therapy gap and a separate 200-300-per-year gene-therapy-eligible pool.
700-900 NHS-diagnosed Fabry patients split cleanly by therapy. Roughly 600 are on enzyme replacement and about 200, or 25%, on oral migalastat, with free NHS cascade testing adding 3-4 diagnosed relatives per index case.
Iptacopan's substantial-benefit finding gave Germany real negotiating leverage over Novartis. Six months on, no negotiated net price has surfaced in the Lauer-Taxe — the pricing signal this model is built to catch before a launch-sequencing decision locks in the wrong assumption.
Both ravulizumab and iptacopan cleared NICE's standard Technology Appraisal route (TA698 and TA1000). The real payer question is how fast the NHS converts patients from IV ravulizumab to oral iptacopan, not which drug got the easier appraisal at the ordinary £20,000–£30,000/QALY bar.
8,000-10,000 US SMA patients split roughly 60/27/13/under 5 percent across Types 1-4. The 500-700-patient Zolgensma cohort is what this funnel validates against.
The GCC's largest rare-disease programme by patient volume sits in a commercial vacuum. Crizanlizumab and voxelotor are both withdrawn, leaving 8,000-10,000 NPHC-managed SCD patients ahead of 2025-26 gene therapy registration.
NICE accepts palbociclib, ribociclib, and abemaciclib as comparators for each other. No trial has ever tested any of them head-to-head against exemestane plus everolimus, the older endocrine-based comparator regimen they effectively replaced.
NPHC has a 72%-cost-reduction incentive to switch amenable-mutation Fabry patients from ERT to migalastat. A single HEK293 assay lab in the entire GCC is the only thing standing in the way.
True UK ATTRwt-CM prevalence runs 20,000-40,000, and 15,000-36,000 of those patients remain undiagnosed. Only 3,000-4,000 are on NHS-commissioned tafamidis today, adding 1,500-2,000 a year.
An estimated 8,000-9,000 Americans live with hereditary angioedema. Just 35-40% receive any prophylaxis, leaving 2,500-4,000 patients who meet treatment criteria untreated, the funnel this model sizes precisely.
All three funded SMA therapies in England reached the NHS through a conditional route. Zolgensma was recommended under HST15 and extended under HST24; nusinersen and risdiplam spent seven years in managed access before TA1162 moved them to routine commissioning.
15,000-20,000 Americans carry a PNH clone, but only about 3,500 reach complement-inhibitor therapy. Up to 1,200 of them stay anaemic on it. This model sizes every gap in between.
600-800 estimated GCC Dravet patients, fewer than 200 SCN1A-confirmed. A 200-400 near-term addressable cohort sits within that confirmed subset.
NICE recommended both Dravet therapies through standard Technology Appraisal, not the ultra-rare HST route. This covers what the Fintepla Cardiac Monitoring Scheme costs the NHS, and why the UK treatment algorithm is now closed to new entrants without a significant clinical edge.
Epidemiology projects 1,200-1,500 GCC HAE patients; the GCC allergy society's own case registry counts only 400-600. The gap is not a contradiction, it is the diagnostic-capacity constraint of just 6-10 specialist physicians across all six states.
NICE TA696, since updated by TA984, opened NHS commissioning of tafamidis for ATTR-CM at scale. Acoramidis's pending appraisal and vutrisiran's TA868 access route are the two other decisions defining the UK amyloidosis market.
~600-750 UK PNH patients are on active complement-inhibitor therapy against a reconciled total prevalence near 1,500. The other 750-900 are monitored-only or undiagnosed, and this model sizes the gap.
France's PMSI hospital database counts 897 PNH patients over five years; Orphanet's older estimate puts national prevalence at 850-1,000. Only 270 of them, per the manufacturer's own estimate, are eligible for a second-line oral agent.
350-450 UK Pompe disease patients, of whom roughly 200 form the registry-confirmed cohort. One in four long-term ERT patients is not holding stable, the segment this model is built to size.
400-600 GCC Pompe disease patients, of whom 200-300 are on enzyme replacement therapy. Just 40-60, patients with FVC decline despite alglucosidase already on home ventilation, are the segment this model is built to size.
NICE has cleared every modern PNH anti-complement therapy through the standard £20,000-30,000 Technology Appraisal route. From ravulizumab to crovalimab, none used the more generous Highly Specialised Technologies threshold, and each went via a confidential patient access scheme.
NHS England's Pompe commissioning policy defines a 45-50 patient switch-eligible cohort for avalglucosidase alfa (NICE TA821). That is a manageable NHS budget event; broader first-line uptake would be a materially larger one.
Migalastat's HST4 recommendation in 2016 was the first oral mutation-specific rare disease therapy NICE approved. Agalsidase beta was never formally appraised at all. Together they underpin an estimated £144M NHS Fabry programme, with a £70-130K/patient/year switch incentive still unrealised at scale.
GCC anti-C5 tender pricing already runs 40-60% of US WAC, anchored to whichever EU comparator prices lowest. A further 10-20% negotiation discount compounds it. Iptacopan has to clear the same cascade, still 12-24 months from SFDA registration.
NICE's SCD gene therapy appraisal may be the largest NHS rare disease budget event in history. It hinges on an annuity payment model that current NHS SCD management cost cannot yet clearly justify.
Agalsidase beta runs an estimated £150-250K per patient per year against migalastat's £80-120K. NICE has quantified that £70-130K annual switch saving but the NHS has not captured it at scale, and pegunigalsidase's TA915 commercial arrangement now sets a third price point.
NICE's accepted 20-35% PAS discount off budesonide's WAC sets the pricing floor sparsentan already clears. The £140-180M NHS budget ceiling applies once the ACEi/ARB gate narrows eligibility to 3,000-5,000 patients.
France's PMSI hospitalisation database identified 897 PNH patients between 2018 and 2022, putting prevalence near 1 in 94,000. That is below the 1-in-70,000-to-80,000 range Orphanet and France's national rare disease plan have long cited.
NPHC pays roughly SAR 1.2-2.4M per patient per year for enzyme replacement against SAR 400-600K for migalastat. That 72% differential gives NPHC a direct incentive to switch eligible patients, capped almost entirely by a single-laboratory diagnostic bottleneck rather than by price.
GCC Dravet pricing is an import-cost problem, not a rebate negotiation. Cannabidiol's Schedule-1-equivalent narcotics classification adds USD 10-15K in compassionate-programme cost plus SAR 5-8K in import logistics, while stiripentol's non-narcotic status keeps it at SAR 30-50K through standard hospital import.
Roughly 5,000-10,000 diagnosed US Fabry patients split first by GLA amenability, with 35-50% oral-eligible. ADA status narrows that to a precise 200-400 patient addressable niche, which a Fabrazyme-anchored $250-350K WAC makes commercially calculable.
NICE has never modelled a cost-per-QALY for a myasthenia gravis biologic. Eculizumab's appraisal (TA636) closed before a dossier was submitted; efgartigimod's (TA1069) closed on evidence gaps, not a quantified ICER breach. A new entrant inherits no reusable comparator or price benchmark from either.
SMA is the most mature rare-disease access model in the GCC. All three modalities are NPHC-covered, with Zolgensma's outcomes-based milestone rebate the GCC-first template other programmes follow.
Casgevy and Lyfgenia list at $2.2M and $3.1M, but the sticker price is not what gets paid. CMS's Cell and Gene Therapy Access Model, Medicaid concentration, and a $1.5-1.9M ICER ceiling decide the realised net.
Both existing Dravet therapies cleared NICE's standard Technology Appraisal, not the ultra-rare Highly Specialised Technology route. A new entrant's WAC, PAS, and stakeholder-engagement calendar all need to be built against that lower cost-effectiveness bar, with soticlestat's 2026-27 appraisal setting the clock.
US Dravet incidence of 1 in 15,700 births is consistent with the Dravet Syndrome Foundation's 6,000-8,000 prevalence estimate. Only 35-40% of that population, 1,400-2,000 patients, remains inadequately controlled on today's two branded agents.
NICE recommended crizanlizumab in 2021, then withdrew the guidance in 2023 when the confirmatory trial failed. The licence was revoked. In UK sickle cell, price is not the binding constraint. Confirmatory evidence is.
Lanadelumab lists near $450,000 a year against berotralstat's roughly $95,000. ICER's 2021 fair-value benchmark for berotralstat lands almost exactly on that list price, and the three 2025 entrants carry no ICER anchor of their own.
Near-universal newborn screening puts the UK's 15,000-17,000 SCD patients on the registry with confidence. But only the 4,000-6,000 hydroxycarbamide-inadequate subset is the addressable population for a new non-gene agent.
NPHC's negotiated Zolgensma price runs $1.5-1.8M against $2.125M US list. But the real mechanism is a 24-month motor-milestone rebate, the same structure now anchoring risdiplam and nusinersen pricing across the Gulf.
Lanadelumab tenders at SAR 300,000-400,000 a year, but NPHC has no routine formulary price at all. Access runs through an individual-case bar only 30-40% of submissions clear, while private VHI approves at a materially lower documentation threshold.
GCC SMA incidence runs 1:6,000-8,000 against a global 1:10,000. Newborn-screening coverage splitting 90%/85%/75% across KSA, UAE and Qatar means the addressable near-term population depends on which country's screening curve a launch model assumes.
Epidemiology implies 1,200-1,500 true GCC HAE patients, but the KFSH&RC registry confirms fewer than 200. A separate planning estimate used for launch work lands at 400-600 — three numbers, one diagnostic-capacity story.
NICE's June 2025 rejection of efgartigimod (TA1069) leaves UK myasthenia gravis with no NICE-recommended novel agent. Eculizumab's own appraisal (TA636) was withdrawn by the manufacturer in 2020 without a cost-effectiveness verdict, and the NHS IVIg cost-offset argument is now the strongest lever for a future resubmission.
The broader estimate puts 12,000-15,000 UK patients with generalised myasthenia gravis. About 4,000 have moderate-severe disease and 2,000-3,000 are refractory, with no NICE-recommended novel agent for any of them.
5,000-10,000 diagnosed US classic Fabry patients face a 35-50% amenable-mutation gate to oral therapy. The treated population is still 60-65% on enzyme replacement. This funnel starts at diagnosis because no defensible undiagnosed estimate exists yet.
6,000-8,000 US Dravet patients, roughly three-quarters SCN1A-confirmed. 35-40% are still inadequately controlled on cannabidiol plus fenfluramine, the population any new agent must actually reach.
GCC male Fabry prevalence runs 1:20,000-30,000, elevated by founder mutations. Only 200-300 patients are diagnosed against a true burden estimated 3-5 times higher, and female diagnosis lags at under half the male rate.
2,000-2,500 UK Dravet patients, of whom 400-500 are SCN1A-confirmed in genetic registries. 600-900 remain inadequately controlled on cannabidiol plus fenfluramine.
A ~1,000-patient confirmed UK SMA cohort by type reconciles against a 1,800-2,000-patient total prevalence estimate. A 50-60/yr Zolgensma cohort is the on-therapy validation anchor.
GCC SMA incidence runs 1:6,000-8,000 births, with newborn-screening coverage from 90% down to under 50%. An 800-1,200-patient legacy Type 2/3 pool and a 60-80/yr Zolgensma cohort anchor the on-therapy view.
Two GCC ATTR-CM burden estimates both convert to fewer than 1,000 confirmed diagnoses. One puts the range at 15,000-25,000, the other at a narrower 2,000-5,000 ATTRwt-CM cohort. This model reconciles the gap and traces it to scintigraphy access.
NICE TA606 commissioned lanadelumab with a PAS and 87.5% real-world attack reduction. Berotralstat's TA738 recommendation is now tested against that same benchmark.
NPHC's well-established Pompe programme still gates avalglucosidase behind a 12-month failed-response switch criterion. Sanofi is pursuing NPHC first-line approval to bypass it.
316,950 annual US invasive breast cancer diagnoses and a 6.0% metastatic-at-diagnosis rate size the incident flow. Layering CDK4/6-inhibitor and post-progression pricing onto that flow, and onto the separate, larger recurrence pool, is what turns a patient count into a market value.
GCC gMG sizing treats the 6,000-10,000-patient disease-landscape prevalence estimate as the authoritative broad base. A 200-300-patient refractory subgroup, fewer than 50 currently on a biologic, is the narrower actionable segment inside it, not a competing total.
6.7 million Americans have F2-F3 MASH, but Rezdiffra has already reported 42,250+ patients on therapy and $311.3M in Q1 2026 revenue. This model triangulates population against real uptake, not a modeled guess.
IQVIA puts the 2023 US T2D drug market at $22B top-down. Triangulated bottom-up against 29.7M diagnosed patients out of 38.4M with the disease, the two methods converge, but per-class revenue split remains an open gap this model flags rather than invents.
Three IV enzyme replacement brands run ~$300,000/year with no generic rival, so preferred-ERT designation is the real pricing lever. Eliglustat's CYP2D6 gate and generic miglustat's trial-first rule complete the picture.
Germany's DGHO Onkopedia guideline states plainly that Germany-specific PNH prevalence and incidence figures do not exist. It borrows 16 cases and 1.3 new diagnoses per million annually from British and French registries, and routes all case-finding through just two national centres, Ulm and Essen.
A GCC nephrology network capacity survey estimates 8,000-12,000 IgA nephropathy patients across the region. The same survey finds kidney biopsy performed in fewer than 30% of eligible proteinuric patients, and zero patients on any SFDA-registered novel agent as of 2024.
An estimated 8,000-12,000 GCC IgAN patients narrow to fewer than 30% ever biopsied, then to zero on novel therapy. No agent is SFDA-registered as of 2024. The funnel gap, not the prevalence estimate, is what a GCC patient flow model has to size.
An estimated 2,000-3,000 Gulf patients carry a clinically significant PNH clone. Only about 400 are confirmed in national registries, and just 150-250 reach complement-inhibitor therapy. Diagnostic capacity, not drug access, is the constraint this model sizes.
NICE accepts a £100,000-300,000 QALY threshold for ultra-rare Pompe disease, five to fifteen times the standard appraisal bar. That Highly Specialised Technologies ceiling is what avalglucosidase alfa's TA821 recommendation used, but only with a substantial confidential commercial arrangement. A new entrant without that leverage should build a standalone case for the antibody-positive inadequate-responder subgroup instead.
The UK's NICE-commissioned Dravet algorithm manages an estimated 2,000-2,500 patients on cannabidiol and fenfluramine. The NHS genetic testing registry logs only 400-500 molecularly SCN1A-confirmed cases — a registry-scope gap, not a population contradiction.
NICE recommends both ATTR-CM stabilisers, tafamidis (TA984) and acoramidis (TA1121), and directs clinicians to the cheaper one. Acoramidis cleared on indirect comparison alone. A third entrant must beat an invisible, PAS-discounted floor, with no published price target.
GCC Dravet prevalence is estimated at 600-800 patients, but fewer than 200 are molecularly SCN1A-confirmed. The 200-400 figure used in launch planning is a distinct near-term actionable tier, not a fourth competing total.
GCC ATTR-CM burden runs 15,000-25,000 on a broad HFpEF-adjacent estimate, or 2,000-5,000 on the narrower ATTRwt-CM cohort. Fewer than 8 centres with scintigraphy capacity explain why so little of either total converts to a confirmed diagnosis.
150,000 US IgA nephropathy patients, of whom 70,000-90,000 are biopsy-confirmed. Only 5,000-8,000 are on novel therapy today, while 15,000-25,000 patients with UPCR above 1g/g remain the addressable high-risk cohort this model sizes precisely.
10,000-15,000 UK IgA nephropathy patients, of whom approximately 8,000 are tracked in the UK Renal Registry. Only 3,000-5,000 clear the mandatory ACEi/ARB and SGLT2i optimisation gate to become eligible for a novel agent, and fewer than 500 currently access one pre-NICE.
All five FDA-approved IgAN therapies clear the same prior-authorisation gate, not a negotiated rebate table. That gate is biopsy-confirmed diagnosis, UPCR 0.8-1.5 g/g, eGFR 30 or higher, and RAS-blockade step-through. No formal net-price data exists because access here runs on step-therapy criteria, not payer negotiation.
200,000-250,000 GCC sickle cell patients, with 140,000-200,000 in Saudi Arabia alone. NPHC's actively-managed registry reaches only 8,000-10,000 — the addressable near-term funnel stage within a much larger under-managed population, not a contradiction.
Fabrazyme's orphan-drug exclusion under the IRA shields it from Medicare price negotiation entirely. No rebate or net-price figure is disclosed anywhere in the primary record for any Fabry therapy. The orphan exclusion, not a discount ladder, is what a Fabry pricing strategy has to be built around.
Two UK gMG estimates disagree by 3-4x on purpose. A narrower moderate-severe subgroup of roughly 4,000 from the MGA UK survey sits inside a broader 12,000-15,000 total prevalence figure that also counts mild, well-controlled cases the narrower estimate excludes.
Wegovy lists at roughly $1,349 a month, but CMS pays $274 for a 30-day semaglutide supply from 2027. That 71% cut applies to Ozempic, Rybelsus and Wegovy alike. Tirzepatide sits outside the negotiation entirely, for now.
Two IRA negotiation cycles have now cut across the T2D formulary. Januvia down 79% to $113, Jardiance down 66% to $197, Farxiga down 68% to $178 from January 2026, and semaglutide down 71% to $274, with Janumet and Tradjenta added for 2027.
US cold agglutinin disease sizing starts from a rate range, not a point estimate. Incidence 0.6-1.2 and 1-year prevalence 1.4-3.1 per 100,000 imply ~5,000 prevalent patients. No published treated-share figure exists to split served from total addressable.
Stelara's negotiated price falls to $4,695 from a $13,836 list, a 66% cut, effective January 2026. That is the same month ustekinumab biosimilars begin launching. Two separate pricing shocks land on one legacy biologic at once.
6,000 US Type 1 Gaucher patients size a market near $1.8 billion at ERT pricing. That MedlinePlus-sourced population sits inside a genetic sub-segment where Ashkenazi carrier frequency runs 1 in 12-15, against a general-population disease frequency of just 0.70-1.75 per 100,000.
Iptacopan's ~$550,000 annual WAC sits roughly 71% above ICER's $156,000-157,000 value-based benchmark. The orphan-drug exclusion keeps anti-C5 incumbents outside IRA's reach entirely. Those are the two forces any new US PNH entrant must price against.
The Leeds National PNH Registry tracks about 600 UK patients on complement-inhibitor therapy. A broader estimate cited in AXLRx's own Launch Readiness research puts it near 1,500 total patients and 1,000 treated. Reconciling which count anchors a sizing model is the open question.
NICE built UK SMA access in sequence, not as an open field. Gene therapy took the pre-symptomatic subgroup first (HST15, HST24), then TA1162 moved chronic therapy to routine funding behind it. A new entrant inherits a fixed subgroup hierarchy and a comparator that shifts by population.
Sutimlimab costs $259,000-$302,000 per patient per year. A peer-reviewed analysis puts its ICER at $2.34M/QALY, with standard of care favoured in all 10,000 probabilistic-sensitivity iterations. The value gap, not a rival drug, sets the pricing discipline.
NICE recommended crizanlizumab (TA743) via managed access in 2021, then withdrew it in 2023 after the confirmatory trial failed. Casgevy (TA1044) cleared only by restructuring its £1.65M price into managed access. A new entrant inherits no reusable ICER benchmark from either.
Three completed NICE standard technology appraisals already fund HAE prophylaxis in England (TA606, TA738, TA1101). Every one cleared at the ordinary £20,000 to £30,000 per QALY bar and is held behind a confidential Patient Access Scheme, so a new entrant inherits a comparator-dense field in which garadacimab's £20,625 list pen is the only transparent price.
NICE accepted an eGFR-slope-to-ESRD-delay model, not headline proteinuria reduction, as the value basis in IgA nephropathy. That covers budesonide (TA937, expanded by TA1128) and sparsentan (TA1074). The mandatory ACEi/ARB and SGLT2 inhibitor optimisation gate narrows the UK's 10,000 to 15,000 patients to a 3,000 to 5,000 novel-agent-eligible pool before that pricing math applies.
IgA nephropathy sits outside NPHC's genetic/orphan disease scope entirely, so there is no GCC formulary price to model. Budesonide clears case-by-case at SAR 80,000-120,000/year through hospital committees or private insurance; sparsentan is not yet tender-priced at all.
Iptacopan's orphan-drug status let it clear Germany's AMNOG process with an established additional benefit and no comparator dossier at all. Ravulizumab's only PNH-specific G-BA review found no added benefit.
US PNH prevalence spans 15,000 to 20,000 patients across three phenotypes, but only about 3,500 are on complement-inhibitor therapy. A 2.4-year average diagnostic delay, plus 200 to 400 patients a year undertreated at non-PNH centres, accounts for most of that gap.
Fintepla's weight-based list price runs roughly 3x Epidiolex. Payers work that gap through step-edit design layered on Part D pharmacy-benefit routing, and no generic cannabidiol reaches the US market before the late 2030s.
500,000+ US patients aged 70+ with HFpEF carry undiagnosed ATTRwt-CM, against only 70,000-100,000 diagnosed and treated. Two further sub-populations, Val122Ile carriers and ATTR-PN, remain even less visible.
An estimated 150,000 Americans have IgA nephropathy, but only 70,000-90,000 are biopsy-confirmed. Just 5,000-8,000 are on a disease-specific therapy today, within a 15,000-25,000-patient high-risk eligible cohort.
Both NHS-commissioned Dravet therapies cleared NICE's standard £20,000-30,000/QALY bar, not the ultra-rare HST threshold. A new entrant is held to the same bar the incumbents already cleared, and total NHS Dravet spend still runs a modest £9-16M.
The UK Renal Registry tracks about 8,000 IgA nephropathy patients against an estimated 10,000-15,000 total prevalence. Only 3,000-5,000 are eligible for a novel agent, and fewer than 500 currently receive one.
France prices PNH on two tracks. Ravulizumab holds first-line; iptacopan is reimbursed second-line only, and reached patients through early access two weeks before its EU marketing authorisation took effect.
US Pompe prevalence runs 5,000 to 10,000 patients, 70-80% late-onset. Of the roughly 2,000 LOPD patients on enzyme replacement therapy, 375 to 600 are inadequate responders, the addressable population any new agent must reach.
Tafamidis prices 12-17x above ICER's fair-value benchmark, yet the orphan-drug exclusion keeps it out of IRA negotiation. Acoramidis and pending generics, not Medicare, now set net price.
Saudi Arabia's rare disease registry counts about 400 confirmed PNH cases. Global prevalence rates, adjusted for the region's 25-50% consanguinity rate, imply a true GCC PNH population 20-30% higher, and fewer than 15 labs across six countries can even run the diagnostic test.
700-900 diagnosed UK Fabry patients split roughly 600 on ERT to 200 on oral therapy. Two niches sit inside that: 50-80 ADA-positive suboptimal responders and 80-120 undertreated symptomatic female heterozygotes, against a £144M NHS spend anchor.
An estimated 100,000 US sickle cell patients narrow to a 55,000-65,000-patient pool with no adequate novel therapy. Only 50-100 of the gene-therapy-eligible minority were actually treated in year one.
NICE's TA1121 cost-minimisation rule directs clinicians to whichever ATTR-CM stabiliser costs less. That rule, not the QALY threshold alone, now sets a new entrant's UK price ceiling.
The UK HAE Alliance counts 5,000-6,000 total patients, of whom 1,500-2,000 are on NICE-commissioned prophylaxis. A further 1,500-2,500 are attack-active but never treated, and Longhurst et al.'s 37-centre registry confirms 1,152 patients from the bottom up.
IgA nephropathy has no NPHC programme at all in the GCC. Access runs entirely through hospital pharmacy committees or private insurance, gated by a biopsy available at fewer than 20 GCC centres.
The most effective Dravet agent is the least accessible in the GCC. Cannabidiol's Schedule-1-equivalent narcotics classification caps exceptional-import approval at 35-40%.
5,000-10,000 Americans live with Pompe disease. Roughly 2,000 late-onset patients are on enzyme replacement therapy, and 375-600 of them, one in four, are inadequate responders, the subtype this model is built to size.
Pompe ERT WAC runs near $400,000 a year, and the Pombiliti + Opfolda regimen splits across Medicare Part B and Part D. Zero ICER reviews exist today, with one expected in 2025 and a 12-month J-code lead time for any new entrant.
200-300 diagnosed GCC Fabry patients sit against a true prevalence estimated 3-5 times higher. A single regional laboratory gates the amenable-mutation test, and female heterozygotes are diagnosed at under half the male rate.
Generalised myasthenia gravis has no formal NPHC programme. Efgartigimod access runs through private insurance, fastest at 1-4 weeks, or hospital pharmacy committees, with NPHC engagement targeted for 2025-2026.
Germany has no domestic PNH prevalence count of its own. DGHO's Onkopedia guideline borrows a 16-per-million estimate from British and French registries, and only two national centres, Ulm and Essen, anchor referral.
Ibrance's Medicare-negotiated price takes effect a full year before Kisqali's and Verzenio's. Three clinically equivalent drugs, staggered IRA negotiation cycles, means Pfizer sets the reference point Novartis and Lilly then have to negotiate against.
ICER priced efgartigimod's value at $18,300-28,400 a year, under half its ~$418,400 assumed launch price. That gap is hardening into a three-tier step-edit staircase across US commercial and Part B plans.
UK Fabry disease is commissioned through three different NICE and NHS routes at once. No formal technology appraisal for either enzyme replacement therapy, a Highly Specialised Technologies recommendation (HST4, 2016) for migalastat, and a standard appraisal (TA915, 2023) for pegunigalsidase alfa. A new entrant inherits no single reusable comparator or price benchmark.
NICE has cleared all four modern PNH anti-complement therapies through its standard £20,000-30,000 Technology Appraisal route. Ravulizumab TA698, pegcetacoplan TA778, iptacopan TA1000 and crovalimab TA1019, each contingent on a confidential commercial arrangement, never the Highly Specialised Technologies threshold. A new submission inherits an unbroken standard-STA precedent it must be built to clear from the first dossier decision.
GCC tafamidis pricing is not one number. Private-import pricing near SAR 820,000-850,000/year describes the pre-registration state; post-registration tender pricing near SAR 70,000-90,000 describes what follows.
316,950 new US invasive breast cancer diagnoses in 2025. Only 6.0% present as metastatic at diagnosis, but 73.9% of the metastatic population is HR+/HER2-, the subtype this model is actually built to size.
NHS-commissioned alglucosidase alfa runs £200,000-350,000 per patient a year post-PAS. Avalglucosidase alfa's NICE TA821 recommendation carries a 20-30% WAC premium and a switch-population budget impact of just £2-4M a year.
At 200,000-250,000 GCC patients, US or UK list pricing is commercially impossible. NPHC's own exceptional-access threshold caps a novel agent near SAR 8,000-20,000/year, a fraction of a $2.2M gene-therapy WAC.
No UK gMG biologic has ever cleared NICE at any price. Eculizumab's manufacturer withdrew before submitting an ICER, and efgartigimod's June 2025 rejection means a future entrant's price ladder starts from zero precedent, not a benchmark.
A ~100,000-patient US SCD population narrows to a 55,000-65,000-patient addressable white space. Only 50-100 gene-therapy patients were actually treated in the first 12 months, versus 200-300 projected.
Zolgensma's $2.125M sticker price obscures the real US SMA pricing lever. A 10-state Medicaid outcomes-based annuity pays $212,500 a year for ten years, set against chronic Spinraza and Evrysdi costs and a Part B/Part D routing split that changes patient cost by drug.
An estimated 500,000+ US patients aged 70+ have undiagnosed ATTRwt-CM, against only 70,000-100,000 currently diagnosed and treated. A separate 100,000+ Val122Ile hereditary carrier pool sits alongside it.
NPHC's annual Pompe ERT budget runs SAR 100-160M across 80-120 patients. That is SAR 800K-1.2M for alglucosidase versus SAR 1.2-1.8M for avalglucosidase. A new entrant should target SAR 2.0-2.5M a year, with switch approvals clearing at only 40-60%.
GCC gMG has no single price. Efgartigimod costs SAR 300,000-600,000/yr through private VHI, a different figure through hospital pharmacy committees, and a third through NPHC exceptional access, with a unified formulary price still 12-18 months out.
National Amyloidosis Centre-anchored epidemiology puts UK ATTRwt-CM prevalence at 20,000-40,000. Only 3,000-4,000 patients are on NICE-commissioned tafamidis today, leaving 15,000-36,000 undiagnosed.
France reimburses iptacopan second-line only, after at least six months on a C5 inhibitor, while ravulizumab holds the first-line position. The restriction, not the price, is what defines the addressable population.
Every SMA therapy the NHS funds entered through a conditional route. Nusinersen and risdiplam sat in time-limited managed access from 2019 until TA1162 moved them to routine commissioning. UK SMA pricing is a question of how long an asset stays conditional.
US gMG prevalence runs 100,000-200,000, but only 4,000-6,000 patients are on FcRn therapy today. 1,200-2,100 of those remain inadequately controlled. The near-term opportunity is the funnel gap, not the epidemiology total.
Three NICE technology appraisals (TA606, TA738, TA1101) each carry a confidential Patient Access Scheme. Garadacimab's published £20,625 per-pen price is the only fully transparent figure in the class, and two MHRA-licensed agents still have no NICE-confirmed net price.
Carrier-rate-adjusted epidemiology implies 140,000-200,000 KSA sickle cell patients. NPHC's structured active-management programme reaches only 8,000-10,000 — a care-registration gap, not a measurement error.