BIOECONOMICS: Biotech Can’t Sidestep Cost-Effectiveness Anymore

Back in the old days of biotech, the business was pretty straightforward. You’d craft your scientific idea, aim a new drug at patients in need, charm investors to give you some money, run bang-up clinical trials, win FDA approval. Do all that, and you’re good as gold. Charge insurers whatever the market will bear, and count the money.

That model worked for a long time, but there’s another hoop everyone needs to jump through now, and I’m not sure everyone in the industry has fully come to terms with it. No matter what happens with President Obama’s healthcare reform in the Supreme Court  or Congress, there are forces now that limit what society will pay for new drugs. We don’t have actual price controls in the law, but the pressure to wring costs out of the $2.6 trillion U.S. healthcare system is intense and will only grow as the baby boomers get older. Drugmakers can’t duck and hide from this issue anymore.

This thought came to mind when reading some medical stories this past week that, as usual, said little to nothing about cost. News came from the American College of Cardiology meeting, where Sanofi and Regeneron Pharmaceuticals (NASDAQ: REGN) released impressive clinical data for their new cholesterol-lowering drug, around the same time similar results came out from Amgen (NASDAQ: AMGN). These drugs are genetically engineered antibodies that zero in on a target called PCSK9. The science is elegant, and the medical need for lowering cholesterol is significant. 

But here’s the rub. Cheap generic statins will surely be working quite well for millions of people by the time these new antibodies hope to reach the market in a few years. Antibody drugs by their nature are expensive to manufacture, and come with much higher price tags than pills. So these antibody makers will have to decide at some point—do we want to charge a premium price for treating a small population of statin non-responders with great needs, or do we try to lower the price and go after a broader market of patients who simply want a more effective alternative to statins? While these new drugs may look good on paper with their ability to bring down LDL counts, insurers preparing to spend real money on these products will rightfully want to know whether these new agents can lower the long-term risk of heart attack, stroke, and death when compared to a statin. That is a very long, expensive, and risky question to ask in clinical trials. 

Even if the drugmakers can answer that question, I just can’t see an antibody drug catching on at $1,000 a month, potentially for tens of millions of people. You can be sure that if the drugmakers aim for the masses with these new antibody drugs for lowering cholesterol, insurers will push back hard. Questions could include: How much hospitalization time will the new antibody save? How many more years will people live on the antibody? How many years will patients on the drug be able to remain in the workforce? How much of the cost burden should patients have to shoulder themselves with co-pays?

These drugs are still in early development, so there’s time to answer these questions. But what we’re talking about is a profound new set of rules for drug development. It’s about showing that new drugs are safe, effective, and save the healthcare system more than they cost.

Alder is a good example of a company that thought about cost-effectiveness back when it was founded in 2004, before this issue became so urgent. The company’s basic technology enables it to produce antibody drugs in fast-dividing yeast cells, instead of the usual mammalian cells. That means Alder should be able to make its drugs faster and cheaper than its competitors. Having a lower cost of raw materials means Alder should someday be able to sell its products at a lower price, while maintaining healthy profit margins. Its pitch to insurers will be about offering what it hopes will be a slightly more effective drug at a lower price. After weighing all these factors—safety, effectiveness, cost-effectiveness—Alder has decided it’s ready to advance its own anti-PCSK9 antibody into its first clinical trial this year, Schatzman says.“It’s not enough to get a drug approved anymore, you need to get people buying it,” says Randy Schatzman, the co-founder and CEO of Bothell, WA-based Alder Biopharmaceuticals. “We’re moving into a brave new world in the next few years.”

Venture capitalists have been taking the new cost-effectiveness mentality seriously for some time now. Brook Byers of Kleiner Perkins Caufield & Byers spoke last November at the Personalized Medicine Conference about how his firm makes a habit of inviting major insurers in to its offices to meet with its partners, and entrepreneurs at its portfolio companies, about what they’ve got to start doing to prove the value of their products—beyond whatever clinical effectiveness goal gets set by the FDA.

Mike Powell of Sofinnova Ventures, which raised a new $440 million biotech fundlast fall, says reimbursement strategy has essentially gone from being a secondary consideration to a primary consideration.

“Reimbursement (which integrates the cost effective issue) is a key issue for us investing in any company, at any stage,” Powell says. “In the distant past, we had this as a ‘secondary diligence item’ for the Sofinnova investment process, but recently it has become one of those ‘front and center’ issues. Which, I must say, is frustrating sometimes, because getting real data on future reimbursement levels is a best-guess prediction for most drugs. Often we are trying to guesstimate reimbursement for a drug that is treating an unmet medical need today—and so there is little guidance as to accurately predict reimbursement levels.”

It’s interesting to see people forced to think about reimbursement this early in the development process, years before companies even think about filing an application to the FDA. Decisions about pricing and health economic pitches to insurers used to be considered only after companies completed the third and final phase of clinical trials, or got ready to submit new drug applications to the FDA, says Chris Rivera, the president of the Washington Biotechnology & Biomedical Association, and a former senior vice president at Genzyme.

Cost-effectiveness and reimbursement have become such important factors that Rivera says he counsels entrepreneurs to consider it from their earliest days in business and to seek out experts on the subject at the University of Washington, Fred Hutchinson Cancer Research Center, and Group Health.

“If I were starting a company today, whether I had a novel compound or was licensing it in, one of the first things I’d look at is whether there is an unmet need, and next would be whether there is a reimbursement strategy,” Rivera says.

There are a number of ideas percolating out there about how the pharma industry can deliver better value for the money. Sam Waksal, the former CEO of ImClone Systems, recently wrote a New York Times op-ed about offering refunds to patients when drugs don’t work—an idea that has been tested in the U.K. and proposed by many others in the U.S. before. This idea is about neutralizing some of frustration patients have about cancer drugs that sometimes cost around $100,000 per patient while offering a few months of extra survival time on average.

While those stories get a lot of attention—ask Dendreon—there are still quite a few companies charging high prices with less resistance. Some of the new personalized medicines—Roche’s vemurafenib (Zelboraf), Pfizer’s crizotinib (Xalkori) and Seattle Genetics’ brentuximab vedotin (Adcetris) for example—have proven they can charge very high prices for their cancer drugs with little pushback from insurers because their drugs are so effective for a well-defined genetic subgroup of patients. Essentially, if you are UnitedHealth, Aetna, or WellPoint, you know that if you pay for one of these drugs, you won’t be flushing three-quarters of the money down the toilet on patients who won’t benefit. Put another way, society is still willing to pay very high drug prices on occasion, but only when we’re really confident it will be money well spent.

As a citizen who pays taxes and health insurance premiums, I dislike waste. I like to see people come up with innovations that save the healthcare system money rather than just add more cost. Healthcare costs are unsustainable at the current rate, but most people would also agree that we as a society want to keep developing new drugs to help us live longer and better lives. The burden is on the biotech and pharmaceutical community to prove that these innovations can do great things both for our health, and for our budgets.

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