Pick your poison: Proleukin or Yervoy

When ipilimumab (Yervoy) got its green light from the FDA a few weeks ago, I assumed it was a conspicuously better drug—safer and more effective—than interleukin-2. It seemed likely that it would immediately begin to push IL-2 aside as the standard of care for patients with metastatic melanoma.

IL-2 (Proleukin) is so toxic that it must be administered in an intensive-care setting at specialty cancer centers. It works in 10% to 15% of patients, in whom about half experience a durable (long-lasting) response. Ipi has not been tested head-to-head with IL-2, but data so far shows that 10% to 20% of MM patients respond to it. When ipi works, patients typically have a full to partial response that can last for years.

So while I’ve heard that melanoma specialists are starting to steer their patients toward ipi, it’s hardly the stampede I half expected. Ipi’s clinical advantages over IL-2 are significant but not overwhelming. Interestingly, it also appears that IL-2 is not going down without a fight. This is a drug that in 2009 had net sales of $75 million. Despite its serious side-effects—most notably capillary leak syndrome—IL-2 is well understood by the melanoma and renal cancer specialists who administer it. There is a momentum to treatment regimes they know and are comfortable with. Nobody talks much about it, but IL-2 is also much cheaper than ipi, which costs up to $120k retail for a full treatment schedule.

Furthermore, ipi comes with a “black box” warning of its own for adverse immunological reactions.

It’s thus not so coincidental that I participated in a marketing survey last week for what will likely be an ad campaign for Proleukin. I saw an announcement at one of the melanoma bulletin boards that was soliciting participants with MM, responded by email, and was soon hooked up with a pharmaceutical marketing firm. This outfit has contracted with Prometheus Laboratories, which markets and sells the drug in the U.S. The marketer interviewed me by phone for about two hours, assessing the communication I’ve had with my oncologist about treatment options, the nature of my relationship with him, and then my response to messages contained in prospective ads for Proleukin. I viewed 12 online ads individually and responded to a series of questions, including whether the ad would motivate me to learn more about the drug. When interviews with a total of 20 MM patients are complete, the marketing firm will submit a report of its conclusions to Prometheus in June.

I suspect I was harsher in my opinion of IL-2 than most others surveyed. My experience three years ago with interferon was an extremely unhappy one, and I would avoid if at all possible another immunotherapeutic agent that’s even more debilitating than INF. I’m also a tough customer in my assessment of ads. I don’t like to be manipulated.

I found several things interesting about this experience:

1. I’m intrigued by the notion of an ad campaign targeted at people who, statistically speaking, are highly likely to die within a matter of months of their disease. Each year, melanoma is diagnosed in about 60,000 people in the U.S. and is the cause of 8000 or so deaths. In the melanoma community then, the ads will be relevant to only a few thousand of us. I’ve never before seen an ad of any type for any melanoma drug.
2. The ads themselves were surprisingly nuanced. The copy accentuated the positive, as you would expect, which includes the long history oncologists have with Proleukin, the response rate and the possibilities of durable responses. Without Yervoy being mentioning by name, its perceived weaknesses were exploited in how the ad copy was written.
3. Prometheus seems convinced that this is turf worth defending. In Big Pharma, $75 million in annual sales is not a lot of money but neither is it chicken feed. With Yervoy now on the market, and other therapeutic drugs for MM in the pipeline, that base is sure to erode. I suspect there's some other strategic reason why this company is investing in this market. Or perhaps it simply wants to beat Bristol-Myers Squibb, which developed Yervoy, to the punch. Could a marketing battle be brewing?
4. A new marketing approach for an existing drug is not as exciting as a new drug that diversifies treatment options, but the Proleukin ads would definitely raise MM’s profile. To put it coyly, it’s nice to be noticed. 

My disease is still treatable by surgery, but should I need systemic therapy, I’d like to know that I have more to choose between than IL-2 straight up and IL-2 on the rocks. Everyone I’ve heard from seems to think that Yervoy will be poaching market share from Proleukin, but my guess is the two drugs will coexist for a time while additional clinical trials are done to provide more specific data on Yervoy’s benefits. As with so many promising treatments before it, the new drug could yet prove to be a disappointment.

There is also the aberration that in cases where metastases are restricted to subcutaneous tissue (as they have been for me), research shows that more than 50% of patients respond to IL-2. To my knowledge, there are no data yet on what the corresponding figure is for Yervoy. It’s also not known what percentage of the responders to IL-2 had durable responses. A virtual cure is what matters most to me—not just knowing that your tumors aren’t growing bigger.

I have an appointment next month with my oncologist, so we’ll discuss this matter then of whether Proleukin or Yervoy makes most sense as a first-line treatment should I need to choose one. It’s also possible there are clinical trials of targeted therapy or other drugs that make sense for me. Proleukin’s ad campaign won’t make a big difference in my thinking, but I’m gratified to know there’s competition for my attention.