Rare and Innovative? Not Enough for European Payers

December 18, 2018 | Disease

Melanie senior

There are no longer any free tickets to access European or US drug reimbursement, even for highly novel drugs that address rare diseases. UK cost watchdog the National Institute of Health & Care Excellence (NICE) and the US Institute for Clinical and Economic Review (ICER) have both turned down two newly-approved, innovative orphan drugs as too expensive.

Alnylam Pharmaceuticals’ Onpattro (patisiran) and Ionis/Akcea’s Tegsedi (inotersen) treat a very rare disease called hereditary transthyretin-mediated amyloidosis (ATTR), for which no other therapies exist. Both reduce disability and enhance quality of life. But Tegsedi costs $388,000 per patient per year in the UK, and Onpattro costs $167,000 – and there’s little evidence as yet that their benefits endure over the longer-term. So NICE declared in late 2018 that neither drug would be an effective use of resources. ICER, faced with $450,000 annual list prices for both treatments, reached a similar conclusion.

NICE’s rejection is preliminary – a review will happen in February 2019 — and ICER’s opinions are non-binding on the US’ multiple payers. But the UK reimbursement process in particular is a familiar dance: manufacturers go in with aggressively priced, highly novel medicines – Onpattro is the first RNA interference (RNAi)-based drug ever approved in the US and Europe –  and NICE says ‘no way’, even with the more generous cost-effectiveness thresholds that accompany highly specialised technologies. Manufacturers come back with a revised price (typically) or some other kind of patient access agreement (less often), and the drug may then get a green light. The approval may apply only to a certain patient groups – though with only about 150 ATTR sufferers in the UK, restrictions may be less likely in this case.

The steps are so familiar that Ionis’ spokesperson admitted that NICE’s decision was “not unexpected”. NICE’s objections tend to cover similar ground, too – besides price, manufacturers are regularly chastised for assumptions made in their economic models and costings, usually biasing in favour of treatment, and insufficient evidence of long-term benefits (a fact of life for new medicines).

One might wonder why sponsors do not check in ahead with NICE – which offers sponsors early advice – and use more conservative estimates. The companies had already offered NICE confidential discounts. But the estimated incremental cost per quality-adjusted-life year (QALY) for Tegsedi was still nearly three times the threshold (per the manufacturers’ own economic model) and over six times using NICE’s preferred model. ICER, similarly, is recommending discounts of between 90-97% for the drugs.

These are not slight adjustments. Nearly 20 years after NICE came into being, the discrepancies between manufacturers’ and payers’ estimates of value can still be vast – even, as in this case, when there is more than one option (Pfizer has a similar drug on the way in a related disease). Alnylam anticipated payers’ value-quest in the US, engaging in discussions around value-based agreements for Onpattro with payers including Harvard Pilgrim Healthcare, Express Scripts, Aetna. That is good. Prices that are closer to payers’ well-publicised thresholds would be even better – not least for patients, who could access treatments faster.