Biogen Idec is developing a test that can tell patients their odds of getting a deadly brain illness from Tysabri.
The screening tool could be marketed as early as 2011 if clinical trials involving 9,000 people show a low rate of false findings. The test is designed to detect the JC virus that causes progressive multifocal leukoencephalopathy, or PML, a brain-cell destroyer that can lead to disability and death. (Tysabri has been linked to 42 PML cases.)
If the test works, it is “absolutely a game changer,” said Patricia O’Looney, vice president of biomedical research at the National Multiple Sclerosis Society. With a false-negative rate of 2 percent, patients who are free of the virus would lower their risk of getting the brain disorder PML to 1 in 25,000 for the first three years of their Tysabri therapy.
And speaking of risk management, I’m chairing a panel on REMS today at the 19th Annual Partnerships in Clinical Trials conference.
A common question I get about REMS is – how is it different from what we used to call RiskMAPS? I see two main differences. The first, obviously and importantly, is that REMS has actual legislative language. And that’s an important detail – but it’s one-dimensional.
The second, more important and contentious difference is the environment into which REMS was birthed -- an environment in which there is growing realization that the 21st century FDA must add a third leg to its mission of safety and efficacy – and that third leg is safe use. The safe use of drugs. And the formulation, implementation and communication of plans – REMS plans -- that will assist physicians and patients achieve better outcomes through the strategies and tactics devised therein.
That being said, there are those in industry and in the broader healthcare policy arena who look at REMS and don’t see GEMS.
Many have looked at the FDAAA language on REMS and see it as an ill-advised green light for the FDA to inject itself into the practice of medicine.
While I agree that REMS does indeed represent an expansion of the FDA's authority, I do not agree that it is either ill advised or an over-extension of the agency’s purview.
The concept of "safe use" as an integral part of the FDA's 21st century mission and REMS as one of many tactics to achieve better patient care are contentious and crucial. And it is that debate which brings us together today.
REMS must be viewed as a “win/win” situation for the agency (which can now move forward to approve drugs with higher risk profiles and have a more direct path for post-market surveillance), for sponsors (who can have their drugs approved with greater alacrity), for physicians (who will – at least in theory) have a more complete view of risks and benefits, and patients (who will have additional therapeutic options and will now – at least in certain circumstances – become a more complete part of the compliance/adherence proposition).
There’s much debate and discussion over where in the drug development process REMS should surface. Acknowledgement that this cannot be done in the absence of data – and confusion as to how to deal with early (even Phase II information) that might be REMS relevant. And “confusion” meaning both scientific uncertainty and internal confusion and discomfort.
There’s evident frustration about validated tools (the absence thereof). But this was at least somewhat assuaged by the timely release of the FDA’s draft guidance on “Format and Content of Proposed REMS Assessments, and Proposed REMS Modifications.” And it was a cool and refreshing draft indeed.
And there’s continued discussion as to whether or not companies should wait until the agency asks – or if sponsors should preemptively (you should excuse the expression) provide an outline of a potential REMS plan. This is important not just as an issue of timeliness (as opposed to having the agency introduce the topic in a complete response letter), but also of responsibility. If, as we all want to believe, the FDA must be both regulator of and colleague to industry, then what are the responsibilities of a sponsor relative to (among many other things) surfacing the REMS issue – and at what point in the process. Nobody said it was going to be easy.
CDER Director, Dr. Janet Woodcock said that, “Safety means doing the right things for patients. FDA must consider post-approval issues as part of a drug’s lifecycle.”
Janet understands that there’s a real difference between “headlines and help.” In other words, REMS and other safety mechanisms can be viewed as either “headlines” about “unsafe” drugs or in a more appropriate context of “safe use.” Janet opts for “safe use,” while others (in the media and elsewhere) seem more predisposed to the other.
According to Woodcock, “FDA does not control the health care system, so our improving the use of marketed drugs, to a great extent, is going to involve influence rather than control.”
“Influence rather than control” is a savvy and sophisticated concept -- one that many of our elected members of Congress could learn from, and one in which REMS plays an important role.
The FDA’s "Safe Use" initiative is the patient-facing sibling of the agency’s “Safety First” pharmacovigilance program. But it's more than that -- it's the FDA reasserting ownership of safety from those who would use it only as a mallet of fear. I will not mention names.
It's important to note that when the FDA announced the warfarin label change the agency (and Larry Lesko in particular) came under attack from critics who asserted that this was the FDA, inappropriately, telling doctors how to practice medicine.
Jane Axelrad, the associate director for policy at CDER, had to say about REMS, “These safety plans allow patients to have continued access to certain medicines for which there are safety concerns that can be managed through appropriate use.”
Whether you say “appropriate” use or “safe” use – the principle is the same – making sure that the risk/benefit analysis of any given therapy is communicated in a lucid and (when required) strident manner.
Sometimes that requires a label change. Sometimes it requires a REMS plan, but it will always require the active participation and leadership of the FDA in partnership with the pharmaceutical industry, physicians, and yes – even patients.
Because no safe use program will succeed without the secret ingredient of patient responsibility.
But does it require additional agency authority. At a recent House Energy and Commerce Health Subcommittee hearing FDA’s Principal Deputy Commissioner Josh Sharfstein said that FDA could use more authority to bring negotiations over a drug's Risk Evaluation and Mitigation Strategy to a close. The agency can require a REMS, he commented, but not specify its contents.
Brand sponsors must implement such a plan, whereas FDA must pay for and operate a communication plan for generic drugs, he noted. Something to think about as we head into the PDUFA reauthorization debate.
