Print BCTV: FDA Pain - FDA's Hamburg on Zohydro; abuse risk, substituting politics for science

FDA Pain

Transcript of BioCentury This Week TV Episode 187




FDA Commissioner Dr. Margaret Hamburg




Rep. Fred Upton (R-MI)

Governor of Massachusetts Deval Patrick

Attorney General Eric Holder


Department of Justice

Drug Enforcement Agency

Health and Human Services



Zohydro ER hydrocodone bitartrate, Zogenix Inc.

Plan B One-Step levonorgestrel, Teva Pharmaceutical Industries Ltd.



Steve Usdin, Senior Editor




STEVE USDIN: I'm Steve Usdin. Governors, senators, even the Attorney General have criticized FDA for approving the painkiller, Zohydro. Today, FDA commissioner Dr. Margaret Hamburg responds. Welcome to BioCentury This Week.


NARRATOR: Connecting patients, scientists, innovators, and policymakers to the future of medicine. BioCentury This Week.


STEVE USDIN: FDA's approval of Zohydro, a long-acting pain medicine, has created a political and medical controversy that's rippling through state and federal government. On one side, people suffering from chronic pain say Zohydro represents a new source of relief. On the other side, many people who are concerned about addiction and overdoses are convinced Zohydro will exacerbate the opioid abuse epidemic.


Politicians, including many close allies of the Obama administration, have called for FDA to reverse its approval decision. Governor Deval Patrick went farther. Taking an unprecedented step, Patrick banned Zohydro sales in Massachusetts. It was the first time a state tried to block an FDA approval. Last week, a federal judge overturned the ban, ruling that a state cannot substitute its judgment for FDA's determination that a drug is safe and effective.


The judge also said that while banning Zohydro may prevent someone from abusing the drug, it also prevents everyone who needs it from receiving pain relief. To explain why FDA approved Zohydro, and time permitting, discuss some other topics, I'm pleased to be joined by FDA commissioner Dr. Margaret Hamburg. Dr. Hamburg, an advisory committee voted 11 to two to recommend against approving Zohydro, governors, senators, even the Attorney General have weighed in, questioning the decision. Why did FDA approve the drug?


MARGARET HAMBURG: Well, I certainly understand the broader concerns that are motivating some of this in terms of the terrible public health burden of opiate addiction, abuse, misuse, and overdose. But there is a need for adequate pain treatment of patients. And Zohydro in fact does represent an important pain medicine for people that respond better to hydrocodone, or if you need to rotate pain medicines because of chronic use, who don't want to be exposed to acetaminophen, which is a leading cause of liver toxicity, often even fatal liver toxicity.


And all of the other hydrocodone products currently in the marketplace are combined with acetaminophen.


STEVE USDIN: There are a lot of other hydrocodone products on the marketplace, aren't there?


MARGARET HAMBURG: There are a lot of other hydrocodone products in the marketplace. They're all combination products with acetaminophen. And there's a belief that Zohydro is in fact stronger than other pain medicines that are out there. But in fact, there are a lot of pain medicines that are at least as strong, in fact, stronger than Zohydro.


And if you take the combination product, which has to be given more frequently at the highest doses, and compare that to the highest doses of the Zohydro, which is extended released long acting and taken fewer times a day, in fact the dosing strengths balance out. I think there are misconceptions about Zohydro as well.


STEVE USDIN: So I want to go through and unpack some of those. So one of the ones that's mentioned -- the Governor of Massachusetts had said this, several members of Congress have said it -- is that Zohydro is somehow super-potent. It's more powerful than other drugs. Another is that it's more addictive than other drugs.


MARGARET HAMBURG: Well, I think one of the common misperceptions is that this is the most potent opiate out there. And that simply isn't true. The second is that the other opiates out there have abuse deterrent formulations. And we wish that that were so. But in fact, almost without exception, the abuse deterrent claims of some of the products really don't hold water when tested.


And the one abuse deterrent formulation that has met the FDA criteria for labeling as abuse deterrence actually only provides deterrence against immediate injection or nasal intake -- snorting. But it does not prevent oral abuse. And the majority of opiate overdose and abuse is through the oral route, not injection.


STEVE USDIN: I want to talk about this idea of abuse deterrent technology. And it seems to me, you can divide it into two different sets of patients or of people. One is people who are legitimately want a drug for pain prevention or pain alleviation. The other are people who are abusing it.


If you're talking about people who actually deliberately want to abuse a drug, is there any deterrent now or even conceivable that's going to prevent somebody who's determined to abuse an opioid from doing that?


MARGARET HAMBURG: Well, certainly not in terms of the formulation of the drug. There is nothing that can, at the present time, deter a determined abuser. I think one of the things that we really as a society need to do is look at all of the issues that contribute to what is a huge public health epidemic of opiate addiction, abuse, misuse, and overdose, and see what are the things that really make the most difference.


And I think we need to look at some of the activities that are going on at the state level in terms of the prescription monitoring programs, the registries that can help identify patients who in fact are excessively using and likely abusing, and also insights into prescriber behavior, because it turns out that a lot awful lot, the majority of the opiate prescribing is coming from a very limited number of prescribers who may not be prescribing appropriately. And then we also have to look at important issues of diversion and what can be done to prevent that. And law enforcement does have a role as well.


And of course, appropriate disposal is key. And a lot of people who have gotten legitimate prescriptions for legitimate pain needs but don't need it anymore may just not know how to appropriately dispose of them.


STEVE USDIN: So a short form for that is to say there's the hardware, which is the drug and abuse deterrent technologies. And then there's the software, which is what you're talking about, the distribution and disposal. We're going to talk about that more. We'll be right back with FDA commissioner Dr. Margaret Hamburg. First, a look at the sobering statistics on opioid deaths.





NARRATOR: You are watching BioCentury This Week.




STEVE USDIN: We're talking with FDA Commissioner, Dr. Margaret Hamburg, about the approval of painkiller, Zohydro. So Dr. Hamburg, one of the concerns about opioids is just the sheer numbers that are out there. The United States is awash in a sea of opioids, especially if you compare it to other countries. Is that going to be the case with Zohydro?


DR. MARGARET HAMBURG: Well, it is, of course, a concern that we want to make sure that any opiate drugs in use is being used appropriately, and for Zohydro, the patient population for which it's indicated is probably a patient population that's already using opiates and so there'll be a change in opiate use pattern, not an expansion. And we expect, certainly, the anticipation at the present time is that Zohydro will be a very small part of the market.


In fact, DEA has to approve an allotment or a quota for manufacturing and the Zohydro quota is a very small percentage of just the hydrocodone component of the marketplace. I think it's 1% or less. So it's not going to be a huge player in the overall marketplace.


STEVE USDIN: So the DEA is Drug Enforcement Administration and they have quotas for how much of these opioids you can manufacture. I want to get back also because we haven't talked about it much about to the patients. There's been a lot of concern about what this approval might mean for abusers and for addiction potential, but there hasn't been much discussion of what it means for pain patients. Who is going to use it and is it really important for them?


DR. MARGARET HAMBURG: Well, we certainly have heard from pain patients and doctors who manage pain patients, and I think that there is a lot of eagerness to have a hydrocodone product that doesn't have the toxic effects of the acetaminophen in the combination. And I think that is an important aspect of this discussion.


I think that we also need to be looking at what are alternatives. Can we develop better drugs that aren't opiates that effectively treat pain? And we're working hard on that. And there are some products in the marketplace now, but I think with advances in science and a recognition of the importance of alternative non-opiate pain meds, this has to be a huge area of focus. It's certainly one that we're pushing with the research community and with product sponsors.


And we can't forget appropriate training of physicians so that they are actually using these powerful medicines appropriately. Making sure that this opiate drug, whether it's Zohydro or any of the other opiate class, whether their patient really needs an opiate. And they should be managing those patients carefully, watching for signs of addiction, and really making sure that they know how to use that drug and that that's the right drug for their patient.


STEVE USDIN: So you mentioned addiction. It's inherent if patients are using opioids, some of them are going to become, one, dependent on it, and then others are going to become addicted to it and you're also going to have abuse. Is there a need for more drugs or for more other kinds of therapies to help patients with addiction?


DR. MARGARET HAMBURG: Yeah. Well, I think we have to take a very comprehensive approach. And obviously, FDA needs to work with a range of stakeholders, but we have some important roles to play. One, of course, is making sure that drugs that are out there are appropriate and meeting patient needs and accompanied with the right systems of oversight. And Zohydro, actually, has been released into the marketplace with more monitoring and oversight and stronger labeling than any other opiate that's out there now, and follow-up studies as well about its use.


But in addition, I think we need to make sure that there's continuing advancement of the field of treatment of opiate addiction and new, better products developed for that. We recently, actually, announced approval of important new advance, an autoinjector for naloxone, which can reverse the overdose, the respiratory depression, and other life-threatening complications of an opiate overdose and can be used in the community by lay providers to save lives. And then the important work we just discussed about developing new non-opiate analgesics.


STEVE USDIN: You know and I want to talk to you more about this autoinjector for naloxone and how that might be used right when we come back. We'll be right back in just a moment.




ATTORNEY GENERAL ERIC HOLDER: "The concern I have and that I share with you about opioids and where they are ultimately leading our country. Their abuse in and themselves have had a devastating impact on our country."




[music playing]




NARRATOR: Now, back to BioCentury This Week.


STEVE USDIN: We're back with FDA commissioner, Dr. Margaret Hamburg. Dr Hamburg, you talked about the autoinjector for naloxone. I'm wondering, who's going to get access to that, and is it really going to solve the overall problem? If you bring somebody back from a possible death, of course that's a great thing, but if that's all you do, isn't there a good chance that they're going to go out and overdose again a week, a month, a year later?


MARGARET HAMBURG: Well, a couple points -- one is, we know naloxone can save lives. We see it in healthcare settings all the time. And that's where it has historically been mainly used. But we know that many overdoses occur in non-clinical settings. And this enables lay providers to save lives by autoinjecting the naloxone.


Importantly though, this is not something that stops there. And even the autoinjector, which speaks to you when you're using it, says, call 911 for ongoing care. So naloxone is a temporary fix. That individual who has received the naloxone needs to be brought in for ongoing medical care. And this is where we can't treat problems in fragmented ways. We need to make sure that when that individual is brought in who has benefited from the autoinjector and is still alive for a second chance, that not only do they get the acute medical care that they need to take them all the way through this overdose circumstance, but also then links them in to other ongoing care for treatment of their addiction, and they likely have other medical needs as well.


But so we have to look at this in a comprehensive way. But the chance to save a life to then assure better care and hopefully treatment for their addiction is a fabulous advance.


STEVE USDIN: So I want to switch gears and ask about the questions around the integrity of the FDA review process, because there's been so much concern about the approval of Zohydro that some states -- Massachusetts, Vermont, some other states are talking about it -- have actually tried to ban the drug in their own state. And I'm wondering what the consequences are of having states take that unprecedented action of overruling an FDA approval.


MARGARET HAMBURG: Well, I do think that it's quite troubling. And I understand the motivation behind some of these actions in terms of the pressing need to reduce the burden of opiate addiction and preventable disease and death. But I think people should step back and really think very carefully about what it means for states or the Congress to start dictating what drugs should be approved and which ones should be withdrawn from the marketplace.


And you can easily look at scenarios that are increasingly worrisome, where because of ideological beliefs or dislike for certain patient categories or other criteria, drugs that could make a difference in people's lives get banned.


STEVE USDIN: So to be more specific, you could easily envision some state legislatures saying that women's reproductive health drugs, contraceptives, or drugs perhaps for abortion would not be allowed in some states if they set a precedent like this.


MARGARET HAMBURG: Certainly. It's an easy next step.


STEVE USDIN: And the other thing that happened here is some senators, some members of Congress have written to the HHS Secretary and asked her to overrule FDA's decision on that. I guess there's one precedent. She did it with Plan B, and the court overruled it. But in general, what happens if we have a political system where political appointees can overrule FDA on decisions that members of Congress don't like?


MARGARET HAMBURG: Well, I think it's very worrisome. FDA has a very carefully defined legal regulatory framework for our decision making. But most importantly, we are driven by the science. And there is a set of scientific database standards for product review and approval. And I think that when individuals who have very different backgrounds and are in the political environment, not the scientific environment, start making the decisions for the public, you can end up in some very worrisome places.


STEVE USDIN: One of the things that's happened -- and there's been a lot made out of it -- was Attorney General Eric Holder expressed concern, bewilderment by FDA's approval of Zohydro. Have you had a conversation with him about that?


MARGARET HAMBURG: I haven't had the opportunity yet. But I anticipate that I will. I certainly have talked with others at the Department of Justice. And I think that when Eric Holder was asked that question, he actually didn't have much background on the specifics. But we're talking about an important balancing act here. And for the FDA, we have perspective, which is really looking at the data and the science with regard to safety, efficacy, medical and public health need. And of course, our assessment of safety does look at addiction potential.


And we're trying to look at overall clinical benefit for patients. Eric Holder's coming from a very different perspective. If he's told there's a super powerful new opiate that's coming to the marketplace that isn't really needed and why is that happening, I think he would say, I'm concerned.


STEVE USDIN: Well, thanks. We're going to be right back to wrap up with FDA commissioner Dr. Margaret Hamburg.




STEVE USDIN: We're back with FDA commissioner Dr. Margaret Hamburg. Dr. Hamburg, I want to shift over to a couple of other topics. There's been some talk -- Fred Upton, the chair of the Energy and Commerce Committee, a Republican, had said that he's interested in FDA reform. He's accused the FDA of being in the Sergeant Pepper era, being in the 1960s.


I don't know if you'd agree with that, but do you think that there's a scope for working in a bipartisan way to streamline or to improve FDA?


MARGARET HAMBURG: Well, I'm really excited by this renewed interest on the Hill in terms of what we do to advance biomedical product innovation. I don't agree with the characterization that we're in the Sergeant Pepper's era. I think that if you just look in the last couple years, huge progress has been made in terms of strengthening the science within FDA, the engagement with the broader product development community, looking at FDA review times, looking at the new tools that we're using for regulatory review. And I think it's making a difference for patients. And we're getting breakthrough drugs out there, first in class drugs out there, and addressing some previously unmet medical care and public health needs.


So it's an exciting time, and I want to work with anyone who's interested to continue the progress that is being made.


STEVE USDIN: You used the word "breakthrough." One of the things that there's been a lot of excitement about has been FDA's Breakthrough Drug program, which is one that tries to work and get breakthrough drugs identified early and get them out there approved as quickly as possible. That's very resource intensive. Do you have the resources to continue doing that, especially if there are more breakthrough drugs like that?


MARGARET HAMBURG: Well, the breakthrough designation and the breakthrough pathway, which was part of recent legislation, has been making a real difference. It's been more popular than we ever thought it would be, and that does put new resource, human and dollar, resource needs on us. But what it basically is, is when a promising new drug candidate comes through that really will change the landscape in terms of addressing an important medical care need, we say it meets the criteria for breakthrough designation.


And then we treat it differently. We are all hands on deck. It's not business as usual. There's early engagement with the sponsor company to really shape the development agenda and what studies need to be done, what approaches so that we can try to move this as swiftly as possible. There's engagement of senior leadership and scientists at FDA.


And it, I think, really is proving its value. On the other hand, if this is the new model going forward, then we're going to have to really rethink both organization within FDA, but we're going to need additional resources in order to sustain this important new approach.


STEVE USDIN: And that's something I suppose will be discussed with Congress at budget time and also when the user fee negotiations come up again for the Prescription Drug User User Fee act.




STEVE USDIN: So you've got this dialogue that you've started with Fred Upton and with other members of Congress on both sides of the aisle about FDA reform. And I'm wondering whether that's a way you can use that to get into a kind of a bigger dialogue about biomedical innovation in America.


MARGARET HAMBURG: Well, I do believe that this is a critical time for us to look at the big picture of how best to advance biomedical product innovation, how to really deliver on the promise of science and technology today for better patient care. And it is about much more than just FDA reform. Truthfully, we could scale back to almost zero days of FDA review, and we would still not have solved the ultimate challenge of translating science into real world products.


I think we really have to look at the ecosystem, and it's a complex ecosystem. And many parts of the ecosystem that influence each other don't usually talk to each other or try to align. And whether it's intellectual property and patent issues or economic policies, incentives and tax credits, how are we investing in science? Are we funding all the right types of science to really make a difference?


Of course FDA reform, both in terms of our business processes so that we're more efficient and streamlined, but also the scientific and regulatory tools that we have to do our job. And and then of course, reimbursement issues, which are now driving a lot of the interest and anxiety about investing in biomedical product development and will influence its future.


STEVE USDIN: So one of the things that I think is important and maybe a little bit troubling about biomedical innovation is that the lag times are so long that the United States, the world, could be falling behind in what it needs to do. And we wouldn't know it until it was too late, unless somebody was really paying very close attention.


MARGARET HAMBURG: Well, I think that's right. And I think that that's why this is a critical moment, because there are enough indicators that we need to be paying attention. Certainly, if we're thinking about biomedical product innovation, not just in terms of what is in fact my primary focus, which is, how can we better deliver on science for people, but also its important role in our healthcare system, in the economy, in our global economic competitiveness. And we know that many other countries are very actively investing in this area of advancing biomedical product innovation as an economic strategy as well as because of patient and medical care needs.


And I think we need to be thinking strategically if we want to maintain our leadership role.


STEVE USDIN: I'm sorry. That's all the time we got today. That's this week's show. I'd like to thank Dr. Hamburg. Remember to share your thoughts about today's show on Twitter. Join the conversation by using the hashtag #BioCenturyTV. I'm Steve Usdin. Thanks for watching.