Monday, April 4, 2011

Big moves in melanoma drug market

Two former colleagues who closely follow the pharmaceutical industry have done me the favor of giving their take on some big moves made recently in the melanoma drug market. After more than a decade of melanoma being a graveyard for drug developers, it's suddenly a hot spot of research activity.

As I posted last week, ipilimumab (trade name “Yervoy”) received its much anticipated FDA approval, making it the de facto first-line therapy for patients with unresectable stage 3 and metastatic melanoma. It may be months, however, before Medicare carriers start to pay for it. And until they do, most private insurers probably won’t. Provenge, a prostate cancer drug approved by FDA last April, only last week received a preliminary go-ahead from Medicare. That decision won’t be finalized until the end of June.

Like Yervoy, Provenge is a high-priced immunotherapy drug that extends overall survival by only a few months. Medicare is legally prohibited from considering price when deciding whether to pay for a new treatment, but with Congress looking to rein in government spending, new cancer drugs are vulnerable to healthcare rationing. You can expect a huge outcry from patient advocates as this becomes apparent.

I’m not sure where all this leaves patients who are no longer allowed to enroll in clinical trials to gain access to Yervoy and yet can’t afford the $120,000 its manufacturer (Bristol-Myers Squibb) says it will charge for the full treatment regimen. The Melanoma Research Foundation is hustling to find answers to questions like this, and has said it will host a webinar about Yervoy in coming days. I’ll definitely be sitting in on that one.

A friend who I worked with in San Francisco years ago, and who is now an independent research consultant to the oncology drug industry, mentioned that Yervoy is the first drug agent to clearly demonstrate a survival benefit in a phase 3 trial. Interleukin-2 never did, although very good long-term benefit has been documented in a small subset of patients (less than 10%). IL-2 is the current standard of care for most patients with metastatic melanoma. It wasn’t a very high bar for Yervoy to clear, which says a lot for how intractable a cancer melanoma is.

“Yes, Yervoy has some nasty side-effects but they actually seem to correlate with response/benefit. The critical thing is to watch for them and treat with corticosteroids promptly,” my friend wrote. Translation: Patients should be happy if Yervoy makes them very sick as it indicates that it may be working.

Another telling comment he offered was: “An important thing to consider is that you need to have a reasonably intact immune system for these things to work; i.e. not one that’s been beaten down with chemotherapy and the disease process. So probably better to not save ipi as a last resort.”

Thanks. I’ll remember that.

On the subject of cost, it appears that insurers and the government will feel compelled to include Yervoy as a new standard of care. As they do with all new drugs, these payers should be able to negotiate the price down. That could lower the standard four-dose treatment to a mere $60,000 or so. Because Bristol-Myers Squibb will want to recover its costs of developing Yervoy, there is fear that the company will sit on other drugs it has in the development pipeline that look even more promising. This may be a rational decision from a business standpoint, but is grossly unethical. It is, sadly, how the game is played.

An analyst report I was forwarded by another ex-colleague who now reports for a pharmaceutical newsletter included several interesting comments. Among them: Ipi should be used in most patients (more than 70%) diagnosed with metastatic melanoma. The potential for durable remissions (“a virtual cure”) is why all eligible patients should get ipi at some point, according to a key opinion leader interviewed for the report.

Until I live in virtual reality, I won’t be satisfied with something called a virtual cure from an unnamed “key opinion leader.” Durable remissions are the holy grail of cancer research, so if ipi/Yervoy brings us closer to it, then I should probably be grateful. More research on this will be reported at the big oncology congress this June.

This analyst report also noted that Bristol-Myers Squibb’s drug “anti-PD1” should be watched closely. In a phase 1 trial, efficacy in metastatic melanoma could be as much as twice that of ipi with half the toxicity. Pressure from the MRF and other groups will hopefully keep Bristol-Myers Squibb from putting phase 2 trials of anti-PD1 in the deep freeze.

It’s easy to get lost in the esoteric details of melanoma drug trials, so I really don’t try. It may become more personal some day, but for now I’m glad to know people who are paid to keep track of this stuff. The Yervoy approval has given melanoma research a big boost and for at least a few days pushed breast cancer research to the sidelines. That’s what happens when a form of metastatic cancer with poor outcomes can finally be treated with something that holds promise. Yervoy is at least a start.

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