The National Institute for Health and Care Excellence (NICE), the body that determines the clinical effectiveness and economic value of new medicines, has increased the cost-effectiveness thresholds it applies for drugs that qualify for its Highly Specialised Technology (HST) programme.
To calculate a drug's NICE cost-effectiveness, NICE uses quality adjusted life years (QALYs).
For standard drugs, their guidelines suggest that £20,000 to £30,000 per additional QALY is good value for money, although there are exceptions.
However, from 1 April this year, the HST programme now applies a more generous threshold (up to £300,000 per QALY) for ultra-rare disease drugs.
Chief Executive Officer at SynaptixBio, Dan Williams, says the change is welcome but that overall the process remains complex.
SynaptixBio, the only company licensed to commercialise treatments for a rare diseases, is currently developing a drug to treat H-ABC, deadly and currently incurable disease.
He says: “I think everyone understands the need to balance the effectiveness of a drug against its cost and that there needs to be some kind of metric against which judgements can be made, but it remains the case that some decisions are taken on a case-by-case basis, so are open to interpretation.”
Rare disease drugs are typically very expensive owing to high development costs and small patient populations, so the decision to approve them for use in the NHS can be incredibly complex and difficult.
The high prices mean these drugs frequently fail to meet cost-effectiveness criteria, resulting in only 1 in 20 of the ~7000 known rare diseases having an approved treatment on the NHS today.
There are not just issues with the NICE process — companies can run into problems before drugs can get onto this pathway.
According to a report from February this year by the Association of the British Pharmaceutical Industry (ABPI), since 2018, only one quarter of rare or ultra-rare disease drugs approved by the Medicines and Healthcare products Regulatory Agency (MHRA) were submitted to NICE for evaluation.
The decline in clinical trial activity during the last few years is further evidence that rare disease drugs are struggling to get to market.
Dan Williams added: “We know first-hand how challenging it is to bring a rare disease drug to market, as we have just recently selected our development candidate for taking forward into clinical trials."
“The MHRA and NICE form vital parts of the system for ensuring drugs are safe, effective and economically viable. However, the process is very demanding and, for a small biotech such as SynaptixBio, can be a serious drain on resources.”
Williams continues: “The criteria applied by NICE for getting onto the HST pathway include the requirement that the drug is for a condition that is both ultra rare and debilitating, which, despite their best attempts at defining, must leave open the possibility of interpretation."
“There are subcriteria, adding a requirement that the disease is a lifelong condition requiring continuous clinical support and that it has an ‘exceptional negative impact,’ concluding that these things will be judged on a case-by-case basis.”
The UK parliament recently published a post where it spelt out the real-world implications of the threshold changes.
The report notes: “For rare and ultra-rare diseases, NICE uses a cost-effectiveness threshold of £100,000 per quality-adjusted life year (QALY) gained. For very large health gains (e.g., >10 QALYs), this threshold can be adjusted upwards, potentially reaching £300,000 per QALY.”
Dan Williams added: “We are always very supportive of any initiative that improves the life-chances of people living with a rare disease."
“Families often struggle for years just to get a diagnosis, then all too often have to be told there is no effective treatment."
“If ways can be found to accelerate the process and reduce the costs and complexities associated with rare disease drug approvals, then everyone benefits.”