UK reimburses Lucentis… at last!

The UK’s medical reimbursement governing body, the National Institute for Health and Clinical Excellence (NICE), is to reimburse Lucentis (ranibizumab; Novartis) jointly with Novartis under a dose-capping scheme, reversing NICE’s earlier, much derided, decision not to reimburse the drug.

Mr Winfried Amoaku, Associate Professor of Ophthalmology and Honorary Consultant Ophthalmologist (Retina Specialist) at the University Hospital, Nottingham; Vice-President of the Royal College of Ophthalmologists, UK; and Ophthalmology Times Europe Editorial Advisory Board member, said, “The final guidance is excellent news for patients with wet AMD who are in need of access to this highly effective treatment.”

The long and winding road In June 2007, NICE had recommended Lucentis for use in just 20% of patients with age-related macular degeneration (AMD), when the healthier of two affected eyes came to clinical attention. The decision provoked outcry from the general public and from the medical community, and NICE received more than 13,000 complaints, prompting the governing body to review the decision.

In December 2007, NICE announced that it would allow reimbursement of Lucentis for wet AMD sufferers in the first eye to come to clinical attention; many primary care trusts (PCTs), although by no means all, continued to follow the initial guidance, leading to several incidences of legal action accusing a “postcode lottery” within the NHS.

A Final Appraisal Document, published in May 2008, recommended that the drug be made available to all sufferers of wet AMD. The newly published Final Technology Appraisal Guidance has confirmed the recommendations of this draft appraisal.

To be eligible for treatment now in the UK, patients must meet the following criteria: best corrected visual acuity of between 6/12 and 6/96; no permanent structural damage to the central fovea; and a lesion size of no more than 12 times the size of the area inside the eye where the optic nerve connects to the retina. The condition must also be in the process of deteriorating. The guidance states that treatment must be halted if Lucentis is proving ineffective and the patient’s vision continues to deteriorate.

Joint reimbursementLucentis will now be made available to sufferers of wet AMD in the UK under the Ranibizumab Reimbursement Scheme (RRS), an innovative collaboration between Novartis, the UK Department of Health (DoH) and NICE. The scheme ensures universal access to Lucentis to all wet AMD sufferers in England and Wales, and is the first such scheme to be implemented in the UK.

The National Health Service (NHS) will cover the cost of the first 14 injections, and Novartis will cover the cost of any subsequent injections. The limit was set at 14 because, as NICE Chief Executive Andrew Dillon - who estimates the cost of Lucentis at £10,000 (approximately €12,645) per eye - explained, this number of injections should result in stable vision for “most” patients and improved vision for approximately one-quarter of all patients, representing a good use of NHS resources.

“A scheme [such as the RRS] will be viable if it is easy to administer and monitor for compliance and violations,” said Mr Amoaku. “In other words, if it becomes unwieldy, then it will fail. Such a scheme cannot be open–ended either, as I do not believe that any manufacturer would sign up to it under those conditions.

“I envisage that, as the costs of new drugs continue to escalate, other manufacturers may follow suit. However, similar schemes may only be possible for other medications, depending on their efficacy, ease of delivery, costs, and the willingness of the manufacturer or the DoH/NICE to enter such a deal,” he added.

According to Mr Amoaku, post-marketing studies of Lucentis suggest that the number of treatments required in the first two years is actually lower than that suggested in the Lucentis Summary of Product Characteristics (SmPC). “Therefore, the scheme looks viable for ranibizumab, because of the perceived efficacy of the drug. This may not necessarily be the case with other drugs where the efficacy is not so good, or the manufacturer, DoH and/or NICE do not have the will,” he warned.

Macugen given the cold shoulderLucentis rival Macugen (pegaptanib; Pfizer), despite being reimbursed by the Scottish Medicines Consortium (SMC), is still not available on the NHS in England and Wales.

“The continued non-recommendation of Macugen for patients with wet AMD is a disappointment,” said Mr Amoaku. “The Royal College of Ophthalmologists had recommended that at least patients who are allergic to ranibizumab receive an alternative drug: pegaptanib. It is not safe for such patients to be treated even with the unlicensed alternative, bevacizumab, simply because there are some similarities in the molecular structure between bevacizumab and ranibizumab,” he added.

NICE has decided not to allow treatment with Macugen despite the appeal by Pfizer on the matter. According to the NICE Appeals Panel, even where patients are sensitive or allergic to Lucentis, Macugen is not allowed as ‘there is no evidence that patients who developed a reaction to ranibizumab could be safely treated with pegaptanib.’ “In my view, however, there is no scientific reason why such an argument should be advanced because there is no similarity between the ranibizumab and pegaptanib molecules,” argued Mr Amoaku.

“This decision unfairly penalises the 3% of wet AMD patients who may be allergic to Lucentis,” he continued. “Such a reaction can result in severe inflammation in the eye that lasts several weeks. This type of reaction to the drug can in itself cause additional damage to the retina, with further sight loss from the wet AMD superadded on to that. In short, patients allergic to Lucentis could be harmed by treating them with this drug, and by not receiving an alternative.

“It is also known that there are other patients who are unable to attend hospital appointments monthly, as is required for Lucentis injections. Experts at the College hold the view that, in such cases, the use of Macugen - which is administered every six weeks, instead of monthly - would be more appropriate.”

Patients currently being treated with Macugen will be permitted to continue until they and their physician agree a suitable time to stop this course of treatment.

Thousands affected while NICE ponderedThe reimbursement of Lucentis is, nevertheless, welcome news to the vast majority of the approximately 20,000 people a year who are newly diagnosed with wet AMD in the UK, but many feel it is a move long overdue.

“NICE has taken two and a half years to come to a decision on this matter,” Mr Amoaku told Ophthalmology Times Europe. “It has been an unnecessarily long and cumbersome process to reach this final guidance document. There is no reason that could justify the long time it has taken to consult formally with stakeholders on each stage of its deliberations. This is especially true as NICE has implemented all but one of the recommendations (regarding the reimbursement of pegaptanib) made by the Royal College of Ophthalmologists in its original submission in August 2006. In Scotland, it took the SMC only a few months to make a decision, and Scottish patients with wet AMD have had both Lucentis and Macugen available to them for over a year now.

“Part of the problem is the continuing absence of an ophthalmologist in Ophthalmology health technology assessments, which is supposedly to avoid bias and to allow transparency,” said Mr Amoaku.

Now that the decision has been made, the UK retina community can breathe a sigh of relief, though frustrations remain. This significantly delayed decision-making process has already had a profound effect on the lives of thousands of people in England and Wales. “It is estimated that over 56,000 patients in the UK (about 50,000 excluding Scotland) have been diagnosed with wet AMD - and, of these, many hundreds of patients have gone blind - since NICE started their deliberations,” Mr Amoaku concluded.