In March, NICE publicly released an official draft guidance concluding that compared to current standard of care, Orkambi does not offer sufficient increased benefit to justify its daunting cost — approximately 8,000 euro per 112-tablet pack. The cost of a 1-year course of treatment is roughly 104,000 euro per year of treatment.
Orkambi has a marketing authorization in the U.K. for CF treatment in people 12 years and older who have two copies of most common CF gene mutation (one inherited from each parent) resulting in a specific genetic defect known as the F508del mutation in the CFTR gene, a leading cause of CF.
The March guidance noted that while Orkambi has been shown to reduce incidence of hospital admissions for people with F508del-related CF, its benefit to lung function appeared to be modest in short-term while long-term benefits remain uncertain.
Orkambi is an oral ivacaftor/lumacaftor combination medication that targets the underlying cause of CF in people with the F508del mutation. The defective CFTR gene causes the production of an abnormal protein that disrupts water and chloride transport in the body especially in the lungs and digestive tract. The result is poor salt and water flow in and out of cells which leads to buildup of abnormally thick, sticky mucus that can cause chronic lung infections, other severe respiratory and digestive problems.
According to the Cystic Fibrosis Foundation and UK CF Registry, approximately half of CF patients in the U.S. and the U.K. have the F508del mutation. An estimated 2,750 people would be eligible for treatment with Orkambi in England alone.
The Cystic Fibrosis Trust is proposing a solution that would see Orkambi provided to all who can benefit from it, while further evidence is collected on the drug’s long-term clinical impact using the UK Cystic Fibrosis Data Registry.
In response to public feedback, CF Trust suggests that additional real-world data should be collected to demonstrate whether Orkambi offers significant benefits over the long-term. But, the committee proposed that if the drug was eventually made available, it should more affordable.
The committee considered the company’s economic model but concluded that the price reduction applied to lumacaftor/ivacaftor after 12 years (assuming introduction of a future low-cost generic) was not acceptable.
In a press release CF Trust Chief Executive Ed Owen said suggested that NHS in England work with Vertex to provide Orkambi to patients and then enable the UK Cystic Fibrosis Data Registry to unravel the treatment’s value more clearly over time.
“It would be ethically unforgiveable if people with cystic fibrosis were treated like pawns in a bigger battle between the NHS and Vertex over price and longer term impact,” Owen said.
The NICE Centre for Health Technology Evaluation’s director Carole Longson, said NICE decision makers understand how important a new treatment is but they can not justify Orkambi’s low benefit and high cost.
“If the company is able to put forward a proposal that provides Orkambi at a cost-effective price, we would welcome it,” Longson said.
Vertex has not forwarded a counter proposal.
Professor Longson has previously been involved in health technology assessment as director of NICE’s Evidence Research Unit, and contributes to several international policy forums, including the WHO advisory group on Priority Medical Devices and the Scientific Committee of the Innovative Medicines Initiative. She is Honorary Professor of Health Technology Assessment at the University of Manchester, U.K. and currently President of Health Technology Assessment International.
NICE has now issued further guidance advising those who disagree with the decision to respond. If no appeals are filed, the decision will be issued as final guidance in July, after which companies will still be able to submit new, cost-effective proposals demonstrating their drug’s cost-effectiveness, which will be considered under a rapid review process.
The Scottish Medicines Consortium (SMC), whose mandate is “to accept for use those newly licensed medicines that clearly represent good value for money to NHS Scotland,” also issued a negative guidance on funding Orkambi.
The SMC noted lumacaftor/ivacaftor, compared to a placebo, significantly increased percent predicted forced expiratory volume in one second (ppFEV1; a lung function measure) by less than 3% at six months and reduced the annual rate of pulmonary exacerbations in patients with the F508del mutation.
The consortium stated: “The submitting company’s justification of the treatment’s cost in relation to its health benefits was not sufficient and in addition the company did not present a sufficiently robust clinical and economic analysis to gain acceptance by SMC, which does not recommend Orkambi.”