NICE Endorses Pioneering Lucentis Reimbursement Scheme, Rejects Macugen in Wet AMD

The U.K. National Institute for Health and Clinical Excellence (NICE) has released its final appraisal determination on ophthalmology drugs Lucentis (ranibizumab; Novartis, Switzerland) and pegaptanib (Macugen; Pfizer, U.S.) in the treatment of wet age-related macular degeneration (AMD). In a nutshell, the cost-effectiveness watchdog has allowed patients to receive treatment for the first eye affected and for Lucentis to be used free of charge on the National Health Service (NHS) if the manufacturer bears the costs of treatment beyond the 14th injection. On the other hand, NICE has rejected rival drug Macugen as an effective use of NHS resources.

In more detail, Lucentis will be free of charge within the following framework:

Patient Specifications

• Best-corrected visual acuity falls between 6/12 and 6/96 (6/12 means that the patient is able to see at six meters what a healthy subject sees at 12 meters);
• Central fovea not irreversibly damaged;
• Lesion size d 12 disc areas; and
• Evidence of disease progression.

Novartis bears the cost of treatment beyond the 14th injection.

Patients respond adequately to the treatment: A protocol to define adequate response will be developed by the Royal College of Ophthalmologists.

NICE based its decision on clinical evidence and a cost-effectiveness assessment. The institute concluded that safety profiles were similar for both drugs and that both treatments were clinically efficacious, although Lucentis was more so. The decision to fund Lucentis and reject Macugen was thus mostly based on the measurement for the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY). The guidance can be appealed against up until 14 April 2008. The institute is aiming for the final binding version to be released by June 2008.

This new guideline is an amendment to controversial June 2007 guidance, when the institute rejected Macugen and approved Lucentis for use only in patients with both eyes affected by wet AMD (see United Kingdom: 14 June 2007: NICE Courts More Controversy in U.K. with Latest Ruling on Blindness Drugs). Wet AMD can rapidly lead to blindness and is caused by the formation of blood vessels in the retina that impede vision. The disease occurs predominantly in women over 50 and the risks of developing it increase with age. Both Lucentis and Macugen inhibit the growth of the blood vessels. NICE estimates that the disease affects 26,000 new patients every year in the United Kingdom.

Outlook and Implications

In effect NICE has expanded the patient population allowed to use Lucentis free of charge on the NHS, while re-iterating that it believes Macugen is not an effective use of NHS resources. This makes the ruling good news for wet AMD patients and Novartis, while leaving Pfizer without a share of the wet AMD market in the United Kingdom.

Interestingly, the institute went back on its earlier controversial ruling that, in accordance with current practice, it is appropriate to treat the better eye in patients with both eyes affected by AMD. The institute took into consideration the "anxiety and depression associated with allowing an eye known to be affected with AMD to deteriorate without treatment", which suggests that the institute does take criticism on board. According to NICE, 70% of AMD patients are affected in both eyes, leaving 30% of patients affected in only one eye. Among those 30%, 10% will develop the disease in the second eye per year.

However, NICE estimated that treatment of all patients affected with wet AMD (providing that they fall into the categories defined by the guidance) was an effective use of NHS resources only if Novartis agreed to bear the cost of treatment beyond the 14th injection. NICE had earlier estimated that 14 injections should be enough for most patients to benefit from the treatment. The dose-capping scheme was actually proposed by the Swiss manufacturer, which is likely to incur costs under this scheme (see United Kingdom: 14 December 2007: NICE Considers Dose-Capping Scheme for Lucentis). However, Novartis must have done the maths and concluded that it could recoup costs with a widening of the patient population. The interesting thing is the unusual nature of the guidance. In an increasingly cost-conscious climate for medicines, reimbursement for Lucentis comes with strings attached. The dose-capping scheme thus adds to the list of options for risk sharing agreements between governments and the industry (see World:5 December 2007: Risk Sharing Agreements: Temporary or Future Trend?).