Why is a $1,575-a-month drug approved and a $7 one isn’t?

Wet age-related macular degeneration is the leading cause of vision loss in people 65 and over – the age at which all Canadians can benefit from public drug plans.

There are two treatments for wet AMD: ranibizumab (brand name Lucentis) and bevacizumab (Avastin). Both drugs are biologics that inhibit blood-vessel growth and leakage into eyes that causes vision loss. They were both developed by Genentech, which is now a subsidiary of Roche.

Treatment of wet AMD with Lucentis costs $1,575 a month for a recommended period of about two years; Avastin costs roughly $7 a month with about the same treatment period.

The Common Drug Review, the national agency that determines if drugs are cost-effective and warrant being included on provincial drug formularies, has given its blessing to Lucentis. All publicly funded health plans have followed that recommendation, but British Columbia and Nova Scotia also allow for Avastin to be reimbursed.

That means Lucentis must be the clearly superior drug, right? It suggests that B.C. and N.S. are sacrificing safety to save a few bucks, doesn’t it?

Well, not so fast.

According to the only head-to-head comparison done in the real world, the ability of the two drugs to stop (and sometimes reverse) vision loss is “virtually identical” if they are given on the same schedule and at the same dose.

The research, sponsored by the U.S. National Eye Institute, involved 1,200 patients. The results were published in The New England Journal of Medicine this year.

Patients taking either of the drugs had similarly low rates of death, heart attack and stroke, But patients treated with Avastin were slightly more likely to be admitted to hospital than those treated with Lucentis – 24 per cent versus 19 per cent. It was not entirely clear if this was related to the treatment.

Yet some groups, such as the Canadian Council for the Blind, are lobbying vigorously for the continued and expanded funding of Lucentis. They would like to see funding of Avastin for the treatment of wet AMD removed entirely. (The better-known Canadian National Institute for the Blind remains pragmatic on this issue, saying funding decisions should be left to governments.)

The CCB argues that Lucentis is far safer than Avastin and that, besides, only Lucentis is approved for the treatment of wet age-related macular degeneration.

The latter is true. Health Canada has approved Lucentis for the treatment of wet AMD; it has not approved Avastin.

But it has not approved Avastin because the manufacturer of the drug, Roche – or its Canadian distributor Novartis – have never asked for approval. (For the record, CCB gets some funding from Novartis.)

Avastin is primarily a cancer drug. It is used commonly for the treatment of colorectal cancer and to a lesser extent for lung, kidney and brain cancers. It has worldwide sales of $6.4-billion annually, including $92-million in Canada, according to IMS Health Brogan, a private company that tracks prescription drug spending. Lucentis has global sales of $1.7-billion, including $177-million in Canada.

Using Avastin to treat wet AMD is an “off-label” use, but off-label use of drugs is fairly common. It does not necessarily imply a lack of safety.

Lucentis and Avastin are essentially the same drug; they have a near-identical molecular makeup, except the molecules in Lucenis are slightly smaller. Both drugs are administered in the same fashion: They are injected through the white of the eye into the central cavity. Numbing drops are used and patients generally feel pressure more than pain.

While the drugs are similar, a damning new report from the Inspector-General of Health and Human Services (the U.S. equivalent of Canada’s federal Health Department) concludes that the manufacturer of the two drugs, Roche, has essentially manipulated the supply to favour the much more costly Lucentis.

Specifically, Lucentis is packaged in a manner that makes it easy to use, in 1.25-milligram injectable doses. Avastin is packaged in vials measuring 100 to 400 mg. That means that, if it is going to be used to treat wet AMD, it has to be repackaged.

There have been hundreds of cases of eye infection – some leading to blindness – among patients treated with Avastin. But, as the Inspector-General noted, all those cases are due to bacterial contamination that occurred during repackaging; the infections did not occur because of the treatment per se.

If the manufacturer packaged Avastin in easy-to-use single-dose vials, as it does with Lucentis, it would have two drugs that are equally effective – one costing $1,575 and the other $7.

Now, that wouldn’t be good business, would it? And, as the Inspector-General points out, what Roche is doing is perfectly legal.

But we have to ask ourselves why our publicly funded drug plans fall for this dupery.

In the U.S., there are roughly 220,000 people with wet AMD. Those patients receive about 700,000 treatments a year with Lucentis, at a cost of $1.1-billion; they receive 936,000 treatments with Avastin at a cost of $40-million.

Put another way, if everyone with wet AMD was treated with Avastin instead of Lucentis, U.S. medicare programs would save $1-billion a year on a single drug.

There are no precise Canadian figures available, but the data on prescription drug sales suggest that, if anything, a far larger percentage of Canadians are treated with Lucentis.

That translates into savings of $100-million plus each year, on a single drug.

It is a tale that underscores the complexity of drug-reimbursement decisions, but one that should also lead us to wonder if we actually regulate the right things (drug prices versus relative cost of drugs) and if the current system does not encourage perverse incentives such as embracing $1,575 drugs when $7 drugs will do the job.

Origin
Source: Globe&Mail