Learning a Little About Drug Companies from The Lancet
Thursday, March 26, 2009
Democrats have made clear that the lifesaving drug industry will soon face politically inspired assaults.
The pharmaceutical industry is programmed to lurch from crisis to crisis. Even the most promising drugs can fail in development, as happened to Pfizer when it spent a billion dollars on a cholesterol drug that failed in a late-stage trial and precipitated Pfizer’s exit from heart drug research altogether. The rare blockbuster success brings huge profits but those profits typically plummet when patents expire, sometimes wreaking havoc on entire firms. And there is government shock—cuts in reimbursement levels, controls over pricing, shifting regulatory standards, and massive litigation.
Now, in addition, the Obama budget and the pronouncements of the Democratic-majority Congress make clear that the industry that has given us so many lifesaving drugs will soon face politically inspired assaults, ranging from tougher FDA standards to expanded controls over drug prices in the Medicare and Medicaid programs. There will be debate, of course, but the pharmaceutical industry will be peeking out from behind the eight ball. The news media and academic pundits will declare that the industry’s best days are behind it, that most R&D money is wasted in chasing after so-called me-too or copycat drugs of negligible clinical value, and that political and financial interference in today’s fumbling and inefficient R&D enterprise would do little harm despite the familiar warnings from economists about undermining research incentives.
Correcting these dangerous misimpressions could fill a book. But for now, let’s take a look at the February 21 issue of The Lancet, one of the world’s oldest continuously published medical journals. Rather left of center in its political orientation, The Lancet has solid drug-industry bashing credentials. Sure enough, the February 21 issue contains an article on the purported evils of international trade and drug patents.
But The Lancet does try to keep doctors up-to-date on at least a smidgen of the onslaught of new information about pharmaceuticals and their clinical effects. And the February 21 issue was no exception. It reports and comments upon clinical trial results for two new drugs. One is Johnson and Johnson’s ustekinumab, which is sold in Europe as Stelara but is not yet approved by the FDA. Ustekinumab is designed to treat psoriasis and a type of arthritis caused by psoriasis. The commentary notes that although we have seen “a rags to riches evolution in the understanding and treatment of psoriasis and psoriatic arthritis,” better treatments are still needed. Ustekinumab is therefore welcomed as a new class of psoriasis drug. In the trial, the drug diminished skin lesions and improved the joint function and quality of life of patients who were not responding to standard treatments. Ustekinumab is a monoclonal antibody (hence the “mab” in the drug name), a kind of drug that harnesses an extraordinary collection of biotechnology tools. Although the first mab was approved in 1986, most arrived in just the last decade, primarily for cancer and inflammatory diseases such as rheumatoid arthritis. That yet another mab would find its place in a medical journal report with no attention to the complex underlying technology says a lot about the extent to which technical progress in pharmaceutical R&D is taken for granted.
The news media and academic pundits will declare that the drug industry’s best days are behind it.
The second new drug is known so far simply as A-002 from Anthera Pharmaceuticals, a biotech firm. A-002 is apparently the first phospholipase A2(sPLA2) inhibitor to achieve success in a midsize trial designed to assess therapeutic effects with an eye to eventual FDA approval. In this trial, A-002 reduced markers of inflammation and LDL cholesterol that predispose coronary heart disease patients to cardiac events. PLA2 inhibitors are designed to work with the statin class of cholesterol-reducing drugs. Statins have revolutionized the prevention and treatment of cardiovascular disease, but they only prevent half or less of heart attacks in patients taking these drugs. Pharmaceutical firms and basic researchers have been engaged in a wide-ranging search for additional therapeutics, many based on the idea that inflammation is a prime cause of coronary heart disease. PLA2 inhibitors are one result of that research, but again, A-002 may fail in testing yet to be completed.
Merely explaining the therapeutic role of these two drugs is a complex scientific exercise; even more challenging to describe is the exquisite understanding of numerous biological processes that provided the foundation for the development of these drugs. On both counts, The Lancet articles were illuminating, but much remains to be learned about the drugs’ biology and therapeutic effects. However, already—as so often happens with pharmaceuticals—the two new drugs are serving as research tools to explore the role of the immune system and inflammation in both cardiovascular disease and arthritis.
You might think that for first-in-class drugs still in testing for initial approval, competition would not be a factor. But competition is seldom absent from the modern pharmaceutical R&D enterprise. In the PLA2 inhibitor class, competition is already active; The Lancet commentary on the promising outlook for this class is entitled, “Phospholipase A2 Inhibitors in Atherosclerosis: The Race Is On.” It describes promising early trials for both A-002 and GlaxoSmithKline’s darapladib. Now that PLA2 inhibitors have begun to show proof-of-principle, it is no surprise that competing firms are hard at work on this same drug class. As for the aforementioned psoriatic arthritis drug Stelara, it has already achieved promising results in a head-to-head trial with Enbrel, an established treatment for psoriasis and certain types of arthritis.
Much more can be learned from this single issue of The Lancet. It contains brief reviews of two therapeutic areas. The article “Major Achievements in Hepatocellular Carcinoma” (a form of liver cancer) emphasizes three points. First, liver cancer—one of the most common cancers—has long defied treatment with standard chemotherapy and even with new “targeted” drugs that have achieved promising results for lung and pancreatic cancers. Second, an impressive series of recent clinical trial results for the biotech drug Nexavar (sorafenib) “has been a major breakthrough in the management of advanced [liver cancer].” In fact, as pointed out in a recent New England Journal of Medicine article, the initial success of Nexavar came after some three decades of failed trials of established cancer drugs against liver cancer. And third, the success of Nexavar has both opened the door to the development of more liver cancer drugs of the same or similar type and forced a reassessment of imaging techniques, diagnostic tools, and treatment protocols. A recent Journal of Clinical Oncology editorial noted, “Clinical trial research in HCC is exploding,” partly because Nexavar “changed the scope of clinical investigations” with a “blossoming of early- and late-stage clinical trials in all [treatment] scenarios.”
Much of the technical progress in pharmaceutical R&D is taken for granted.
Still working through the February 21 Lancet, we find a piece summarizing what is now known about the genetic, molecular, and environmental drivers of rheumatoid arthritis and how this knowledge is translating into numerous beneficial therapies and revolutionizing clinical practice. It features a series of innovative drugs, introduced in the past decade, that have changed the face of this disease from one of inescapable disability to one with effective preventive and treatment strategies.
Finally, the February 21 Lancet contains a review entitled “use of tumor-responsive T cells as cancer treatment.” This highly technical article summarizes recent findings that could yield important new cancer treatments if R&D organizations (presumably for-profit firms) undertake the incredibly costly and uncertain research necessary to find and demonstrate the safety and effectiveness of those treatments. Most of the discussion focuses on experimental therapeutic cancer vaccines—that is, agents that energize the immune system to attack established cancers, rather than prevent illness as vaccines ordinarily do. Unfortunately, FDA testing standards will have to be revised. FDA normally requires cancer trials to focus on certain established endpoints such as mortality or occasionally, tumor size, which usually means that trials have to involve late-stage cancers. Therapeutic vaccines, however, are probably much more effective against early-stage cancers.
The above is a rather rich array of results and investigations for innovative drugs, all in a single issue of one major medical journal. What about the following week’s Lancet, you ask? Well, check out the article on a new drug from Acorda Therapeutics that is the first to improve the walking ability of a subset of multiple sclerosis patients. Or look at the March 5 issue of The New England Journal of Medicine with its articles on yet another new monoclonal antibody, mepolizumab from GlaxoSmithKline, which offers not only a new treatment for a particularly difficult form of asthma but is helping open the door to a new understanding of this condition.
All of this is something to keep in mind the next time the news media amplify yet another elite medical journal article critical of the pharmaceutical industry. Most doctors, most of the time, read these journals in search of new information about, among other things, better drug treatments for their patients. Fortunately for us all, they find a lot.
John E. Calfee is a resident scholar at the American Enterprise Institute. Elizabeth DuPre is a research associate in health policy at AEI.
FURTHER READING: Calfee recently wrote for The American about Maurice Hilleman and the most cost-effective medicines ever developed. And Calfee is the author along with Claude Barfield of Biotechnology and the Patent System: Balancing Innovation and Property Rights.
Image by Darren Wamboldt/The Bergman Group.