Health Business Blog

Health care business consultant and policy expert David E. Williams share his views

Gene Therapy II

Today’s Boston Globe reports that venture capitalists are starting to invest in gene therapy companies again. The first companies were founded in the mid to late 1980s and failed about 5 years ago. The death of teenager Jesse Gelsinger in a U Penn clinical trial in 1999 started to bring the first era of gene therapy to an end.

The new companies, Applied Genetic Technologies (AGTC), Ceregene, Celladon, Genetix, and Introgen Therapeutics hope to learn from the mistakes of their predecessors. They are improving delivery technologies and being less ambitious on the diseases they target, focusing, for example on diseases that are caused by a single gene. (The Globe article cites my former LEK Consulting colleague Chris Ehrlich of InterWest Partners, which funded AGTC.)

Gene therapy is not the only example of a biotechnology to begin with great hype, disappoint investors and patients, and eventually return to prominence in a new and improved way. A close analogy is monoclonal antibodies.

The first monoclonal antibody was produced in 1975. In the late 1970s and early 80s many articles in the popular press referred to monoclonals as “magic bullets.” The first monoclonal antibody was approved by the FDA in 1986, but then nothing else was approved for eight years. Many clinical trials for cancer failed from 1983 to 1993, and it was only in the late 1990s, after the technology advanced from mouse based to humanized antibodies that antibody based drugs began to fulfill some of their promise. Only now are monoclonal antibodies becoming a significant commercial success.

I hope that gene therapy will work in this investment cycle. If monoclonals are a guide, however, it may take a third round. In 1989, the Wall Street Journal ran an article about how the problems of the original monoclonals had been solved, and proclaimed that, “The long awaited era of magic bullets may now be imminent.” But they were about 10 years too early.

New autism findings pose challenges for regulators

A study presented yesterday at the Experimental Biology 2005 conference in San Diego revealed that many autistic children have low levels of glutathione, an antioxidant that protects against cell damage from oxygen free radicals.

According to the Boston Globe,

The finding is suggestive… because glutathione… is crucial for neutralizing toxic heavy metals such as mercury. [Lead author S. Jill James said,] “One interpretation of this finding is that children with autism would be less able to detoxify and eliminate these heavy metals.”

There is a long-running controversy about whether mercury contributes to autism, and I’ve posted recently about another study that demonstrated a correlation between autism and mercury emission levels in Texas school districts.

Assume for a moment that the findings from the new study hold up, and that a small percentage of people are vulnerable to low levels of mercury in the environment. It provokes some serious questions for environmental regulation:

  • Do we try to set mercury emissions levels so low that no one is harmed? Do we attempt to balance economic benefits with harm done to peoples’ health?
  • Do we expect everyone to get tested to learn their predisposition to mercury poisoning and take steps on their own to avoid mercury (e.g., from fish)? Who pays for the testing?

There are close parallels in pharmaceutical safety:

  • How many moderate, severe, and fatal side effects should we tolerate before a drug that works for some people is pulled from the market?
  • With the advent of pharmacogenomics, can we identify the people who would be harmed by a drug and help them avoid it? Who will pay for the tests?

An early warning to the orthopedic industry

The Justice Department is investigating consulting agreements between orthopedic device companies and orthopedic surgeons. The probe is narrow so far, focusing on whether the companies pay some doctors who don’t provide meaningful consulting services.

The probe is likely to bring increased scrutiny to the orthopedic market, and the industry would be wise to prepare now to explain its common practices to the general public, who will be surprised when they learn how things work. Consulting fees for doctors have been questioned in the pharmaceutical industry as well, so the initial Justice Department questions won’t arouse much public interest.

However, most people will be surprised when they learn that orthopedic sales reps are often in the operating room to assist or guide orthopedic surgeons in performing procedures, and often lend surgical tools as well. They may also be surprised that successful orthopedic sales reps can do almost as well financially as the surgeons they sell to. And the large dollar amounts of some of the consulting relationships will also be surprising.

There is a business and medical rationale for all of this, but it will take a skilled public relations effort to explain. It’s easy to imagine how that could go awry or be neglected, in which case we’ll see much more exciting headlines than the Wall Street Journal’s “Orthopedic Firms’ Ties With Doctors Scrutinized.

Medicare’s Hospital Compare website goes live

You can now check hospital quality performance on heart attack, heart failure, and pneumonia at Medicare’s Hospital Compare website, the Wall Street Journal reports. Seventeen commonly accepted quality measures are tracked and almost all hospitals report their data.

The information should help hospitals improve their performance, private and public payers to implement pay-for-performance systems, and consumers to make better choices. It shifts the focus from whether to report to how to make the information better. And it will likely spur implementation of electronic medical records and computerized physician order entry systems that improve the ability to achieve high scores on the quality measures.

Health plans have some of this information, but have long lacked leverage to negotiate with prestigious academic medical centers. Costs are higher for health plan customers as a result. I’ll be watching to see how health plans use this tool to encourage patients to use lesser known community hospitals that score highly and are less expensive.

Fatigue and cognitive decline in MS

There’s a moving story about a man’s struggle with multiple sclerosis (MS) on the front page of today’s Wall Street Journal (After Diagnosis, A New Dilemma: What to Tell Boss?). Kenneth Bandler hid his disease from his employer because he was afraid he would be pitied at work and constantly asked about his condition.

The article reports that many MS patients leave the work force, “often long before disabilities required them to.” An expert cited in the article believes it may be due to cognitive problems that MS patients suffer.

I asked Dr. Robert Paul, a Brown University neuropsychologist who has studied MS and cognition, for his opinion.

One of the most common debilitating side effects of MS is fatigue. When people feel tired, they feel that they can’t perform well on cognitive tasks. But it turns out that their cognition doesn’t suffer as much as they think when they are tired.

We did a study where we gave MS patients a cognitive test, then a test designed to fatigue them, and then a followup cognitive test. MS patients did not perform quite as well as healthy controls on the cognitive tests at the beginning of the assessment, and they reported much more fatigue than controls. Further, MS patients reported significantly more fatigue after the work battery compared to controls , and they thought their cognition had suffered. But it turned out they did just as well on the followup cognitive test as on the initial one.” These findings suggest that fatigue may not have a significant additional impact on cognitive function in MS.

Part of the problem is a lack of sufficiently sensitive cognitive test batteries. Dr. Paul has been involved in the development of new, sensitive computerized batteries as part of the Brain Resource Company.

The reference for the study is Paul, R., Beatty, W.W., Schneider, R., Blanco, C.R., Hames, K. (1998). Cognitive and physical fatigue in multiple sclerosis: Relationships among self-report, objective performance and depression. Applied Neuropsychology, 5 (3), 143-148.