ANNOUNCER: For most people with multiple sclerosis, medication is important to help slow the progression of the disease. In the early 2000s, clinical trial evidence was growing that a new drug might prove more effective than the medicines then currently available.
FREDERICK E. MUNSCHAUER, MD: There were two large prospective clinical trials using natalizumab, which is also known as Tysabri…And, at the end of those trials, when the patients were coming off after two years, it was quite clear that Tysabri was indeed the next generation of MS therapy.
People had fewer exacerbations, a 68% reduction in exacerbation rate, essentially twice as effective as any of the interferons or Copaxone. And a 42% reduction in the probability of going on to sustained worsening in physical impairment, as measured by one of our scales…
ANNOUNCER: The drug was approved by the FDA for use in November of 2004. But within three months, startling news led the manufacturer, following discussions with the FDA, to voluntarily withdraw natalizumab from the market.
ROBERT FOX, MD: The drug was approved in late 2004. But in February, 2005, there surfaced two reports, and these were… reported to the manufacturer of natalizumab, of a very serious brain infections. And this was a very rare brain infection that we typically don't see at all. It's an infection that is called progressive multifocal leukoencephalopathy. And that's quite a big mouthful. So we call it by its initials, or PML.
ANNOUNCER: The manufacturer and the FDA quickly began an investigation into the two cases of PML in MS patients, and in a third case, in a person with Crohn's disease who had also used natalizumab.
FREDERICK E. MUNSCHAUER, MD: So, in concert with a number of worldwide experts in progressive multifocal leukoencephalopathy and in cooperation with the FDA, the manufacturer reviewed meticulously every single person who had ever been given natalizumab or Tysabri in order to determine whether there were any other cases out there. And this process took the better part of a year.
The investigators found no more cases of PML. There were three cases among more than 3,000 people who were treated with natalizumab.
ROBERT FOX, MD: Once the surveillance was complete the question turned to well can this drug come back out on the market again. It was fairly clearly established that the risk of PML was in the area of one in a thousand MS patients that had treated over an 18 to 24 month period. And was that reasonable to allow it back out on the market, or was that too risky?
FREDERICK E. MUNSCHAUER, MD: And in the late Spring of 2006, an independent FDA advisory panel was brought together to review the results of the full safety inquiry that had been conducted over the previous sixteen, eighteen months.
That advisory committee voted unanimously to reintroduce the drug, but in a more controlled way with more safeguards, what's called a risk map, a procedure that would allow us to identify any adverse events that would occur or safety concerns that would occur going forwards.
ROBERT FOX, MD: Several safeguards were put into place.When the drug was reintroduced, and they really center around a system, a system to control the drug being dispensed, and a system to monitor for cases of PML.
FREDERICK E. MUNSCHAUER, MD: In order for a patient to receive Tysabri, first of all, the prescribing physician, must be specifically trained in the use of this drug, its appropriate indications and the safety concerns that have been identified to date.
Secondly, the person giving the infusion, the nurse or the infusion center, must also go through a rigorous training process where they once again are alerted to the risks and benefits of this drug and what to look for if -- if PML is suspected.
ANNOUNCER: The third safeguard is to ensure that the drug be prescribed only for the type of MS in which it was tested -- relapsing forms of the disease.
Doctors must also prescribe natalizumab without any other type of immune-suppressing therapy, because there may be a compound effect, increasing the chances of developing PML.
ROBERT FOX, MD: A very important aspect about current treatment with natalizumab is that it is to be used only as a monotherapy. It should not be combined with other MS medications.
ANNOUNCER: The new rules call for the use of natalizumab in cases where patients have failed on other medications. But there remains some room in the guidelines for doctors to use the drug initially, in some very aggressive cases of MS.
ROBERT FOX, MD: And so that wording is that it is generally indicated for patients who have not responded or who have not tolerated standard, injectable therapy. And that leaves open the option for clinicians to use it as a first line therapy in patients who we don't feel comfortable waiting the six or 12 months waiting to see if an injectable therapy will work.
ANNOUNCER: Doctors say it was important to re-evaluate the safety of natalizumab after the cases of PML were discovered. But the consensus also seems to be… that its re-introduction gives doctors and patients an important option in treating a disease that can often become debilitating.
FREDERICK E. MUNSCHAUER, MD: Clearly, nobody wants to see you get a 1 in 1,000 chance of having a potentially fatal viral infection. However, when balanced against the disease itself, then the be- -- then the risk-benefit equation clearly shifts in favor of allowing patients and physicians to make the choice, depending upon their perception of the relative risk.