The drug regulatory system is directed towards the approval of new medicines for particular uses, based on clinical trials and other evidence that the product is effective and safe. Yet, once approved, it is in most jurisdictions possible for a doctor to prescribe the product for whatever use s/he sees fit. This is in accordance with the Hippocratic oath, and accepted despite the apparent incompatibility with drug regulation.
However, we have an increasing surveillance by the payer of the use to which a drug is put. In the UK, beyond the process for medicine approval, there is a subsequent hurdle in order for the drug to be reimbursed. NICE (National Institute for Clinical Excellence) was establised to assess value for the National Health Service. In its evaluation, NICE looks at the cost-effectiveness of the use of the drug in the particular indication under consideration.
Thus, NICE initially approved the use of the anti-cholinesterase drugs rivastigmine, galantamine and donepezil for moderate Alzheimer’s disease while rejecting the case for reimbursement of their use in the more prevalent, early stages of the disease. It was only significantly later that the approval was extended to mild cases.
The situation with regard to ranibizumab (Lucentis) and bevacizumab (Avastin) is another case in point. Both products are monoclonal antibodies targeted to the VEGF receptor. Avastin is approved for the treatment of certain types of colon, lung, kidney and brain cancer, and Lucentis is approved for the treatment of wet age-related macular degeneration. Lucentis costs over 10 times as much as Avastin — a price that led some NHS trusts to refuse to pay for the treatment for AMD. After pressure from patients, Lucentis was eventually approved by NICE for reimbursement in 2008. Avastin, on the other hand, has never been approved for ophthalmic use, and has never been reviewed by NICE for AMD. Lucentis is provided by Novartis and Avastin is provided by Roche.
With this analysis, it is no surprise that Novartis has initiated a judicial review of the NHS sanction of the use of Avastin for AMD. This would indeed seem to be a prima facie case where the rules around reimbursement have not been followed. Given the clearly separate processes involved in prescription and reimbursement, at least as far as the UK is concerned, we need to go back to the situation whereby a doctor can prescribe freely, without regard to therapeutic indication, and ask whether tighter rules coupling prescription and reimbursement are warranted.
As I pointed out in a previous post, many secondary uses for existing drugs are not developed, despite the cost and efficiency advantages of repurposing. (One has only to consider that there is scientific evidence for over 30 potential uses for statins, yet no product based on these drugs being developed for any of these new uses.) Innovators would rather develop an entirely new active ingredient and obtain the full patent and data exclusivity thereby due in order to avoid the possibility of off-label generic use of their product, repurposed for a new indication. This is neither in the interests of patients, who must wait longer for the innovation to reach the market, nor of payers, who must pay ‘new prices’.
A reimbursement regime which properly takes account of the therapeutic use, and avoids substitution of a product newly patented for a secondary use, can result in faster innovation cycles and better cost control for the payer. This system avoids the criticism sometimes levied against changes of this kind, that pharmaceutical companies will endlessly patent minor variations in therapeutic utility in order to evergreen their product; this is because the reimbursement needs to be tied to a regulatory change, and one that doctors will see as important enough to re-define their patients.
In my view, together with the changes to data exclusivity advocated previously, this is a better system for patients, payers and innovators alike.