Three completed NICE standard technology appraisals already fund HAE prophylaxis at the ordinary £20,000 to £30,000 per QALY bar, so a new entrant inherits three comparator and ICER precedents at once, and the HTA problem shifts from proving precedent to choosing the right comparator and inferring net prices three confidential schemes hide.
NICE has issued three positive standard technology appraisals for HAE prophylaxis in England, and each one matters differently for a new submission. Lanadelumab (Takhzyro), recommended under TA606 in October 2019, is restricted to patients eligible for C1-esterase inhibitor prophylaxis under NHS England's commissioning policy, and its post-PAS net cost is estimated at £180,000 to £200,000 a year. Berotralstat (Orladeyo), recommended under TA738 in October 2021 for patients with two or more attacks a month, lists at roughly £133,121 a year before a confidential discount and carries a mandatory three-month stop rule. Garadacimab (Andembry), recommended under TA1101 in October 2025 on the same two-attacks-a-month threshold, prices at £20,625 per pre-filled pen, the only fully transparent list figure in the class even though its appraisal also sits behind a confidential Patient Access Scheme. All three cleared the standard £20,000 to £30,000 per QALY bar, not the more permissive highly specialised technology route.
That precedent density is a materially different starting position from an indication with no completed appraisal, and it reshapes the HTA strategy. The comparator is no longer obvious: a new prophylactic must decide whether lanadelumab, berotralstat or garadacimab is its true comparator, and each choice pulls a different net price, administration route and stop-rule expectation into the economic model. Because every recommended agent hides its net cost behind a confidential simple-discount scheme, the pricing case has to reverse-engineer a plausible net-price corridor from the two transparent anchors, berotralstat's £133,121 list and garadacimab's £20,625 pen, rather than read a published benchmark. Our gap register treats comparator selection and net-price inference as the two submission-blocking questions, scored before the dossier is drafted, alongside the live donidalorsen and sebetralstat appraisals that could move the comparator set again before a new agent reaches committee.
UK HAE prophylaxis precedent — three standard-TA recommendations at the same QALY bar, every net price confidential
| Agent | NICE Status | Recommendation Basis & PAS | Comparator / Price Signal for New Entrant |
|---|---|---|---|
| Lanadelumab (Takhzyro) | TA606 (16 Oct 2019) | Recommended, restricted to patients eligible for C1-esterase inhibitor prophylaxis; confidential PAS | Est. net £180,000-£200,000/yr; £20-30K/QALY cleared; subcutaneous mAb comparator anchor |
| Berotralstat (Orladeyo) | TA738 (20 Oct 2021) | Recommended for ≥2 attacks/month; mandatory 3-month stop rule; confidential PAS | ~£133,121/yr list before discount; oral comparator; net cost undisclosed |
| Garadacimab (Andembry) | TA1101 (8 Oct 2025) | Recommended for ≥2 attacks/month; confidential PAS | £20,625 per pre-filled pen, only fully transparent list figure; monthly subcutaneous mAb comparator |
| Donidalorsen / sebetralstat | In NICE appraisal, no final guidance | MHRA-licensed; NICE draft guidance stage, no confirmed decision | Could reset the comparator set before a new agent reaches committee |
| C1-esterase inhibitor prophylaxis | NHS England commissioning policy (no NICE technology appraisal) | Commissioned nationally through a clinical commissioning policy, not via a technology appraisal | Baseline prophylaxis eligibility gate that TA606 references, not a QALY-priced comparator |
Sources: NICE TA606 (lanadelumab), published 16 October 2019; NICE TA738 (berotralstat), published 20 October 2021; NICE TA1101 (garadacimab), published 8 October 2025; NICE in-development project pages for donidalorsen and sebetralstat; NHS England Clinical Commissioning Policy for C1-esterase inhibitor prophylaxis.
What this model answers
Every section answers a named commercial question your team is asking, scoped to your asset.
Delivers
- The 3-test comparator defence applied across a subcutaneous mAb, an oral kallikrein inhibitor and a monthly anti-FXIIa mAb
- How route, dosing frequency and the berotralstat stop-rule each pull a different comparator into the model
- Why TA606, TA738 and TA1101 give three usable precedents rather than one, and which one a given target profile should anchor on
Delivers
- The Net-Price Corridor method: bounding three confidential schemes from berotralstat's £133,121 list and garadacimab's £20,625 pen
- How lanadelumab's estimated £180,000 to £200,000 net cost frames the upper corridor for a mAb prophylactic
- The acute-therapy cost offset (C1-inhibitor and icatibant rescue) that supports the incremental economic case
Delivers
- How an unresolved donidalorsen or sebetralstat decision could reset the comparator set before a new agent reaches committee
- What the three-month berotralstat stop-rule precedent implies for a new agent's continuation criteria
- A pre-submission timeline built around the UK HAE Alliance real-world outcomes evidence and the specialist-centre commissioning interface
Custom model delivered in 72 hours.
Commission This ModelWhat's inside
- Why comparator selection and net-price inference, not the absence of precedent, are what a new HAE submission must solve first
- Pressure-tested against three completed standard appraisals (TA606, TA738, TA1101) before the rest of the model is built out
- NICE's standard technology appraisal route and why all three HAE prophylaxis recommendations cleared the ordinary £20,000 to £30,000 per QALY bar
- The NHS England commissioning interface, the C1-esterase inhibitor prophylaxis commissioning policy that gates lanadelumab eligibility, and the devolved SMC and AWMSG positions
- Population defined on the two-or-more-attacks-a-month threshold NICE anchored TA738 and TA1101 to
- Comparator, intervention and outcomes built where three recommended agents already occupy the comparator slot
- The 3-test comparator defence applied to a subcutaneous mAb, an oral kallikrein inhibitor and a monthly anti-FXIIa mAb
- Choosing between the lanadelumab, berotralstat and garadacimab precedents by target profile, route and evidence base
- Bounding three confidential Patient Access Schemes from the two transparent anchors, berotralstat's £133,121 list and garadacimab's £20,625 pen
- How lanadelumab's estimated £180,000 to £200,000 net cost frames the upper end of the corridor for a mAb prophylactic
- 5-module, 15-check self-assessment against submission readiness in a precedent-dense field
- Testing the dossier against the comparator choice and the acute-therapy cost offset that support the incremental case
- Comparator selection and net-price inference scored separately by likelihood of being raised and impact if raised
- Submission-blocking versus manageable classification, and how the three-month berotralstat stop-rule precedent shapes continuation criteria
- Economic model type selection and the acute-therapy cost-offset inputs (C1-inhibitor and icatibant rescue in inadequately prophylaxed patients)
- Milestone timeline incorporating the UK HAE Alliance real-world outcomes evidence and the live donidalorsen and sebetralstat appraisal clock
- The open HEOR, comparator and pricing 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 claim is pressure-tested through the 3-test defence framework before being accepted, and every net-price estimate is bounded to a stated corridor rather than presented as a single confidential figure.
UK hereditary angioedema HTA sources: NICE TA606 (lanadelumab, 2019), NICE TA738 (berotralstat, 2021) and NICE TA1101 (garadacimab, 2025), the NICE in-development project pages for donidalorsen and sebetralstat, NHS England's C1-esterase inhibitor prophylaxis commissioning policy, and the UK HAE Alliance real-world outcomes survey (2022-2023).
- Each NICE technology appraisal number (TA606, TA738, TA1101) verified against the live NICE guidance page for the exact drug and indication, not inferred from FDA or EMA approval status
- Berotralstat's £133,121 annual list price and garadacimab's £20,625 per-pen list price verified against the live NICE TA738 and TA1101 guidance pages
- C1-esterase inhibitor prophylaxis confirmed to sit under an NHS England clinical commissioning policy with no NICE technology appraisal number, and described without one accordingly
- Donidalorsen and sebetralstat confirmed as in NICE appraisal with no final decision, based on the live NICE in-development project pages
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