|Selected news articles which highlight important policy issues.||
News: Weekly Archives
News for the week of 03-01-2005
Biogen Inc. and Elan Corp. have pulled their highly promising new multiple sclerosis drug, Tysabri, off of the market and suspended clinical trials with the drug following the death of a patient taking it along with an older MS drug, Avonex. Another patient has tested positive for the same rare neurological disorder.
Tysabri was recently granted accelerated FDA approval after initial clinical trial data showed it was “about twice as good as existing drugs in reducing flare-ups of symptoms in MS patients, such as tingling, double vision, and muscle weakness.”
The FDA continues to very supportive of the Tysabri, and most observers believe that it will eventually be returned to market. However, what is alarming about this case is the flurry of criticism that has emerged of the FDA’s accelerated approval program, which is meant to speed patient access to new, promising treatments for life-threatening illnesses. Critics have immediately painted this as another instance of the FDA putting drug companies before patient safety. But the reality is that accelerated approval is a vital tool for getting new drugs to patients with cancer, AIDS, or Alzheimer’s - months or years faster than might be the case under the normal FDA approval process. Comparisons of the Tysabri withdrawal to Vioxx are just inappropriate.
Somehow, we have to recall the reality that disease is our common enemy - not corporations. Other treatments approved through FDA accelerated approval - like antiretroviral treatments for AIDS, or Gleevec for leukemia - have been met with universal praise and applause. But, as the adage goes, how soon we forget.
The reality is that drugs (new or old) - like surgery, or radiation, or chemotherapy - can have tragic unintended consequences. Pills are no different, and no more inherently morally suspicious, than these other instruments of medical progress. Progress depends on accepting some adverse events. Without accepting that trade-off, we wouldn’t have open heart surgery, bone-marrow transplants, or Gleevec. Striving for perfect medical safety would bring progress to a complete grinding halt.
Are Too Many Unproven Drugs Receiving FDA Early Approval? Process Comes Under Scrutiny
A bit more background on accelerated approval at the FDA.
Accelerated approval was originally launched by the FDA in the early 1990s in response to criticism from AIDS activists that patients were dying waiting for new treatments to negotiate the lengthy clinical trials needed for FDA approval. Traditional clinical trials depended on validating “endpoints” for proving efficacy - like a survival benefit, i.e. did the patient live longer - that might take years to validate.
Instead, the FDA created an accelerated process whereby promising new treatments for life-threatening diseases could be approved using “surrogate” endpoints - for instance, the amount of circulating AIDS virus in a patient’s blood stream - that might translate into clinical improvements. In return for accelerated access to the market, companies would have to agree to conduct additional clinical studies validating the treatment or risk drug withdrawal.
Does accelerated approval risk missing rare but serious adverse events with new treatments?
The problem is that rare adverse effects are just that - rare. There is no guarantee that they would be identified in the normal approval process, and no reason to suppose that even this adverse effect should hold up a drug as promising as Tysabri. Slowing down acclerated approval in the hope of identifying more potential side effects - including drug-drug interactions, which seems to be the problem in this case - will only keep new treatments away from patients who desperately need them, without necessarily improving drug safety.
Why is Tysabri important?
Autoimmune diseases like multiple sclerosis - including Crohn’s disease, rheumatoid arthritis, and lupus - are amongst the least understood diseases. Doctors can do little more than suppress symptoms or delay the inevitable. Worse yet, even those few treatments that work to some extent (like steroids or immunosuppressants) have devastating side effects of their own.
The withdrawal of Tysabri has “dimmed the hopes of patients with three different debilitating [autoimmune] disorders.” Tysabri had a different mechanism of action than other drugs used to treat MS: binding to immune cells and preventing them from crossing the blood-brain barrier to attack nerve cells. “The different mechanism of action raised hopes that Tysabri could prove a savior for patients who aren’t doing well on the other drugs and also might be used to boost the effectiveness of other treatments.”
“For Crohns’ disease, Tysabri appeared to provide significant relief to half of the patients, and disease remission was long term in half of those…Those are excellent odds for Crohn’s, which is so severe 80% of patients need to have surgery to remove the affected part of the bowel.” All of the extant treatments for Crohn’s “have potentially serious side effects”, including liver toxicity and increased risk of tuberculosis or lymphoma.
This is the hidden side of how the quest for drug “safety” affects patients with diseases for which there are no safe options. Shouldn’t these patients be able to decide for themselves if a potential benefit from a new treatment is worth the risk?
Administration considers pay-for-performance for Medicare providers
As we noted earlier in our discussion of patient compliance, offering financial incentives for better disease management is getting a lot of attention in the health care world, particularly in government programs trying to stretch their limited health care budgets just a bit farther.
This charge is being led by Medicare Administrator Mark McClellan as “the Bush administration [overhauls] the way it reimburses Medicare providers by financially rewarding those who meet certain standards and punishing those who don’t.”
This may, of course, seem like a radical idea, until you remember that this is the way businesses that actually have set budgets work. Suppliers who meet their contracts get more business. Those who don’t will see their funding streams slashed or be replaced by firms that can provide better quality services.
Medicare’s enormous and rapidly growing budget is, of course, a prime target for pay-for-performance measures, and demonstration projects are already underway that are testing how effectively they work. While performance pay might not slow spending, McClellan is confident that “a change in reimbursement methods would have the potential to affect the bottom line for health care providers” and giving them real incentives to improve quality - which in this case, means patient health.
Warning for Cholesterol Drug
The FDA is adding a warning label to the statin drug Crestor “that starter doses should be reduced in Asian-Americans and some other patients.” Crestor, like other statin drugs, can lead to a serious, even potentially fatal, muscle wasting condition. However, one clinical trial has turned up specific evidence that “levels of Crestor in Asian patients were double those of Caucasians taking the same dose, increasing the chance of muscle damage.”
“The new label urges physicians to start Asian patients, those with severe kidney disease, and patients taking cyclosporine at the lowest dose level. The lowest available dose would be five milligrams, compared with a maximum dose of 40 milligrams.”
Now, imagine that you are a doctor with a access to one of Roche’s AmpliChips. You can measure how your patients will metabolize statins like Crestor, and change dosages and drugs depending on the results. That’s better than any warning label the FDA can supply on a package insert.
Its always easy to overstate the benefits of new technology, but in this case the hype is probably well deserved.
“In January, Roche, the Swiss drugs and diagnostics group, and Affymetrix, a US genetics company, announced US regulatory approval for the first market application for their revolutionary AmpliChip diagnostics technology…Simply put, the [AmpliChip] uses breakthroughs in genetics to isolate individual genes – called bio-markers – uniquely identified with certain medical conditions. Crucial parts of the genes are replicated to make them usable for diagnostic purposes.”
The first chip sounds like a Star Wars robot - CYP450 - but it will help doctors gauge patient sensitivity to a “to a wide range of commonly prescribed drugs.” Now that the basic technology behind the AmpliChip has been mastered, other similar chips will follow that build and improve the same design. For instance, AmpliChip P53 will provide “a cancer test to determine how aggressively a tumor may grow” and consequently what kinds of treatments should be brought to bear by physicians.
Roche is at the cutting edge of medical progress because it is creating the diagnostic tests that will drive drug development over the coming decades. After all, if you understand and can effectively test for biomarkers for diseases like cancer or Alzheimer’s you can use that knowledge to improve drug development and then guarantee effectiveness - and reimbursement - once your products are launched.
Drug blocks cravings
Eat less. Quit smoking. Cut back on the drinking. Sound too good to be true?
“Acomplia, a drug soon to be submitted for Food and Drug Administration approval, could help by effectively blocking [cravings that lead to over eating or smoking]. Even better, there’s promise that it can help people stop smoking and possibly curb alcohol abuse…”
Patients in clinical trials taking Acomplia “lost an average of 20 pounds in a year as well as 3 inches off their waists. In addition, their HDL (good) cholesterol rose about 25 percent. Twice as many smokers were able to quit as those who tried quitting without taking Acomplia, and they did so without gaining weight.” The NIH is planning a trial to see if Acomplia can help reduce alcohol abuse.
This drug, if approved, will have enormous appeal to physicians and patients. But do we have the right safety procedures at the FDA to ensure that it is used as effectively and safely as possible?
Now is the time for the FDA and industry to focus on making sure that “blockbuster” drugs like Acomplia come equipped with the underlying diagnostics and safety monitoring tools to prevent another Vioxx-like scandal.
|home spotlight commentary research events news about contact links archives|