Latest Drugwonks' Blog
Nature Biotechnology reports:
Having Hamburg, who is a “tough cookie,” remain at the FDA provides something of a “public health bulwark against political intrusions,” says Pitts.
The full article, Cuts loom over research and industry following Obama re-election, can be found here.
Yesterday I participated on the Pennsylvania BIO-sponsored panel, “Election Aftermath: The Fiscal Cliff and the Future of Healthcare Reform.”
You might have heard of these issues.
My fellow panelists were Senator Bob Casey (D, PA), Congressman Jim Gerlach (R, PA) and Gary Karr (Executive VP, AdvaMed). The panel was expertly moderated by Chris Satullo (Executive Director of News and Civic Dialogue at WHYY).
Much of the evening’s focus was on the collision of healthcare innovation and national healthcare policy – and not in a good way.
Specific items of discussion were IPAB – Uncle Sam dictating (for tens of millions of Americans) what treatments will be available for physicians and patients; PCORI – the government instructing physicians as to how to practice medicine, FDA reform (specifically surrounding the issue of predictability), waste in Medicare and Medicaid, the medical device tax (both Casey and Gerlach are for repeal of the tax), the President’s call to roll back biologics exclusivity from 12 to 7 years (both Casey and Gerlach are for preserving 12) and, of course, the issues surrounding state exchanges.
Since states are the laboratories of innovation, governors should be given wide authority to design programs that best fit the needs of their particular situations. Ultimately states will learn from each other. HHS waivers should be broad. We’ll see.
The worst scenario is a one-size-fits-all top-down approach that fits everyone poorly. Alas – that’s a pathway preferred by many inside the Beltway. A key issue here is that of essential health benefits, what are they and who makes the call.
Congressman Gerlach was especially effusive (and appropriately so) of the free-market design of Medicare Part D. Lower than expected costs, high utilization and user satisfaction. And he strongly agreed this is a model that can work in the design and implementation of state exchanges.
Jim Dandy.
Senator Casey mentioned his strong support of NIH funding. I suggested to the Senator (politely) that perhaps more than a small slice of that largesse should be redirected to the FDA.
Does White Oak have a friend in Pennsylvania?
Nature reports:
FDA under pressure to relax drug rules
Industry says antibiotic pipeline is being blocked by overly stringent clinical-trial requirements for new treatments.
The latest skirmish in the battle between human and microbe played out on 29 November in a hotel conference room in Silver Spring, Maryland. There, an assembly of scientists and clinicians debated the merits of an experimental antibiotic. For some, the coveted prize was not just an endorsement of the drug itself, but a sign that the US Food and Drug Administration (FDA) is finally ready to rethink its clinical-trial requirements for antibiotics — requirements that the drug industry says are unrealistic.
The number of FDA approvals of new antibiotics has dropped even as multi-drug-resistant strains of bacteria have proliferated. FDA advisers at last week’s meeting did recommend approval of telavancin (Vibativ) — a derivative of vancomycin — for the treatment of hospital-acquired pneumonia when alternative drugs are not suitable. But that vote came nearly two years after the FDA had rejected the drug for a second time because clinical data did not measure up to the agency’s guidelines.
“The agency has painted itself into a statistical corner,” says Scott Hopkins, chief medical officer of Rib-X, a drug company in New Haven, Connecticut, focused on antibiotics. “While the infectious-disease community was crying out for new antibiotics, the FDA seemed to be going in the opposite direction.”
Many trace the agency’s tougher stance to the scandal surrounding telithromycin (Ketek), an antibiotic approved by the FDA in 2004 and later linked to liver failure. In 2007, the US Congress launched an investigation into whether the FDA had ignored staff concerns about Ketek’s safety. The following year, the agency convened its advisers to discuss antibiotics then under review. “Four drugs representing over a billion dollars of investment went into that week and only one came out alive,” recalls Mark Leuchtenberger, president of Rib-X.
Telavancin was caught in the changing tides. When Theravance, the company in South San Francisco, California, that developed the drug, designed the large phase III clinical trials needed for approval, the FDA simply required a demonstration that the drug eliminated symptoms of infection as reliably as the approved antibiotic vancomycin. But, after Theravance submitted its second application on 30 June 2010, the FDA decided instead that applicants needed to show that patients were no more likely to die — of any cause — within 28 days of treatment with a new drug.
Theravance scrambled to gather the data, hunting down medical records for 1,419 out of the 1,503 patients scattered across dozens of countries that were enrolled in the telavancin trials. But the FDA determined that the study lacked statistical power and asked for new clinical studies. Theravance refused, and a stalemate followed.
Strict clinical guidelines for antibiotics have dogged the industry ever since, with pneumonia providing a good illustration. Patients who contract pneumonia in hospital are already ill, making it hard to know if the treatment under review played a part in their death. That means trials have to be larger to capture enough deaths to have any statistical meaning. This, combined with the relative rarity of infections that warrant the use of new antibiotics and the further FDA requirement that patients not receive other antibiotics before they get the experimental drug, has set the goal out of reach, argues David Shlaes, who runs Anti-Infectives Consulting in Stonington, Connecticut. Not a single new antibiotic for hospital-acquired pneumonia has been submitted for approval since the new guidelines were put in place. “The trial simply cannot be done,” says Shlaes. “Whoever was writing these guidance documents doesn’t live on the same planet that I do.”
However, since the Ketek scandal, the political winds have reversed. This summer, Congress passed a set of measures to encourage antibiotic development. In May, Janet Woodcock, head of the FDA’s Center for Drug Evaluation and Research, pledged to “reboot” the antibiotic-approval process. And in September, the FDA told Theravance that its advisers would take another look at telavancin, resulting in last week’s vote.
Investors have also noticed these changes, says Leuchtenberger. Last week, Rib-X announced that it had raised US$18.7 million to help the company start phase III trials of an antibiotic that could target skin infections. “Without some of these positive developments this year, you’re looking at a number of companies that might not be around any more,” he says.
Shlaes, however, emerged from the telavancin meeting still doubtful, noting a continued focus on all-cause mortality. He says that, for now, he will continue to advise his clients to apply for approval in Europe first, where regulators have not been as demanding as the FDA. “I’ve been very optimistic about the whole thing,” he says. “But the FDA has to do something to show that it is actually rebooting.”
I was pleased to chair the Fifth Annual Risk Management and Drug Safety Summit.
REMS is a tactic. Safe Use is a strategy and Safe Use is the new normal.
Some take-aways:
According to Greg Fiore, MD (Chief Medical Officer and Acting Head of Global Pharmacovigilance at The Medicines Company), we are now in a “new world order” where pharmacovigilance teams finally have a seat at the table. But, per Fiore, we are still spending too much time, talent, and treasure of process – and not nearly enough on insights development and use.
Good points. Could this be because ever-more process is a good excuse for actually doing something? Such action would require not just more dollars and FTEs for PV teams – but would also mean changing the cognitive mapping of the way many companies do business. It might actually mean that patient safety takes priority over marketing and sales.
Fiore also mentioned the need to consider what benefits a more aggressive use of social media might mean for pharmacovigilance.
Is it time to “friend” Gerald Del Pan?
Josephine Torrente, JD (a Director at Hyman, Phelps & McNamara), made the point that REMS is labeling (a view held by most at the conference) and that the implications for shared REMS must be taken into account – especially when it comes to biosimilars. Josephine also addressed the issue of possible FDA waivers from shared REMS programs. She doesn’t see it as likely.
Is this another possible point of political intrusion? As with Plan B, will the HHS Secretary decide to grant such a waiver if the FDA declines to do so? Ms. Torrente feels petitioning the Humphrey Building for such divine intervention would have little chance of success. Glad to hear that.
The class-wide Opioid REMS was much on everyone’s mind, and Stuart Kim, JD (Senior Regulatory Counsel, Covidien), made a strong case for a more active role by state-level stakeholders. The context for this was the crucial need to differentiate the desire to address abuse versus misuse. The failure to recognize the different nature of these issues will lead to negative and unintended consequences. He also asked, per the CME requirements, why we are not looking to a more thoughtful level of measurement. Just “ticking the box” on CME won’t solve any problems. Rather, Stuart pointed to a goal of a Moore’s Scale Level 7 achievement of actually improving patient outcomes.
For more on Moore’s Scale, see here.
Addressing abuse is one thing – but smartly dealing with misuse (while not as sexy or politically potent) is at least of equal import.
After Stuart’s presentation, I offered the following prediction:
FDA will not approve generic opioids minus the innovator-developed abuse-resistant technologies – unless they are forced to. IP issues? You bet. Watch this space for more on this issue as it rises to the top of the FDA agenda. (And don’t be thrown off-guard by what’s going on north of the border.)
Eleanor Segal, MD (Consultant, Segal PV Systems), discussed pharmacovigilance trends in the EU, with specific focus on how the EU is actually becomes less harmonized both between it’s own members – and with the FDA. And the new EU directive on Phase IV studies didn’t give anyone a warm and fuzzy feeling.
James Frame, MD (Medical Director, David Lee Cancer Center, Chair of ASCO REMS Working Group, and President, West Virginia Oncology Society) spoke about the “onerous” burdens that many REMS plans are placing on physicians. Not news, but he made the good point that such burdens impact patient access issues such as time spent with physician, availability of support staff to address patient needs – both of which could actually lead to less optimal care. Unintended consequences – but certainly not unpredictable when both sponsor and agency fail to take the weight of “practice burden” into account.
It’s the risk of risk mitigation.
Maybe its time for the FDA (and sponsors) to engage a “physician representative” when it comes to REMS design.
Day One ended with a thoughtful presentation by former FDAer Lynn Mehler, JD (Partner, Hogan Lovells). Lynn predicted that the FDA would be looking forward to more class-wide REMS.
We shall see.
Richard Hermann, MD (Safety Science Physician, Patient Safety, Global Regulatory Affairs, AstraZeneca) brought the issue of risk/benefit analysis via a validated grid into the conversation. His baby, the BRAT, is only one methodology under discussion – but it is an important one in the “date versus information” debate. He urged the audience not be prisoners of process and to fight cultures that are resistant to change be they in industry or at the FDA. He acknowledged that many firms are operating in a “change-weary environment.”
Well, if the Pope can start tweeting and off-label promotion is protected free speech, there is hope for us all.
What will tomorrow bring.
Fasten your seatbelts.
Court: off-label promotion protected
The U.S. Court of Appeals for the Second Circuit said in a 2-1 ruling in United States v. Caronia on Monday that the "government cannot prosecute pharmaceutical manufacturers and their representatives under the [Food, Drug and Cosmetic Act (FDCA)] for speech promoting the lawful, off-label use of an FDA-approved drug." In the ruling, Judge Denny Chin wrote that so long as the off-label use of the FDA-approved drug is legal, the government's interpretation of FDCA's misbranding provisions to prohibit and criminalize the promotion of off-label use "unconstitutionally restrict[s] speech." FDCA prohibits misbranding, but does not expressly prohibit the promotion or marketing of drugs for off-label use. Chin noted that off-label promotion that is false or misleading is not protected by the First Amendment. In a dissenting opinion,
Judge Debra Ann Livingston said the ruling "calls into question the very foundations of our century-old system of drug regulation," adding that if drug companies "were allowed to promote FDA-approved drugs for nonapproved uses, they would have little incentive to seek FDA approval for those uses."
The case concerns Alfred Caronia, a former specialty sales consultant at Orphan Medical, which was acquired by Jazz Pharmaceuticals plc. He was convicted in 2008 of conspiracy to introduce a misbranded drug into interstate commerce based on audio recordings in which he promoted the off-label use of narcolepsy drug Xyrem sodium oxybate. Caronia, who was sentenced to one-year probation and 100 hours of community service, appealed, arguing that his conviction was based solely on his speech and therefore violated his First Amendment rights.
The appeals court vacated and remanded to the lower court the decision convicting Caronia.
So I did some rough calculations: According to CMS the percent increase in Rx filled per year in Part D from 2007 -2009 was 5.6 percent. That lead to an increase in part D spending of about 5.7 billion. Assuming a 5.6 percent decline in the rate of medicare spending I come up with a savings of $30 billion. (The additional spending that would have occured in the absence of drug utilization.) That means every dollar spent on Part D saves about $6 in Medicare spending. Lichtenberg estimates $1 dollar of drug spending on new drugs saves $7. This is a bit below his estimate (few new drugs were introduced since 2006) but now CBO has essentially "blessed" the offset
According to “Pay it Forward,” Medical Marketing & Media’s overview of 2013 …
After a tumultuous few years of healthcare policymaking, the recent election brought a big victory for Obamacare. It's now all systems go for the law, with sweeping change for the American healthcare system and tens of millions more insured. Expect this status quo to be anything but boring.
ACA implementation isn't the most immediate cause for anxiety among healthcare policy types. That honor goes to the “sequester,” a high-stakes game of budgetary chicken set to play out over the next month or so. Last year's standoff between the White House and Congressional Republicans over the “debt ceiling” was resolved, in classic Washington fashion, by kicking the can down the road a bit, but with a twist—if the two sides couldn't agree on painful cost savings by January 2, a legislative “trigger” would be tripped prompting brutally deep cuts (of $1.2 trillion over nine years) to defense and social spending. Medicare is largely exempt from the cuts—limited to 2% of its budget—and Medicaid and CHIP are off-limits. FDA, however, would face deep cuts—projected at $318 million—that would slow approvals and rules-making, according to the Office of Management and Budget, and effectively freeze PDUFA.
“Sequestration would be a complete disaster for all involved,” says Peter Pitts, former FDA associate commissioner. “The FDA simply doesn't have any slack in its budget and would not have the bodies to do things on time. This is not the status quo but a significant step backwards.”
The rest of the article can be found here.
NEW YORK (AP) — Rose Wang looks at her staff of 70 employees and wonders if she'll have to lay off some of them to comply with the health care law.
The owner of Binary Group Inc., an information technology firm based in Alexandria, Va., is one of many small business owners who will be required to provide health insurance for her staffers under a provision of the law that goes into effect on Jan. 1, 2014. Wang already provides insurance, but she has struggled with premiums that have soared as much as 60 percent annually, so she requires employees to contribute to their coverage. She's worried because she doesn't know how much she'll have to pay under the Affordable Care Act.
Wang's worry is a gut-wrenching dilemma that many small business owners are concerned that they may face. Now that President Barack Obama has won re-election, the health care overhaul, which presidential candidate Mitt Romney promised to dismantle, is marching forward. Companies must decide before the start of 2014 what they'll do to comply with the law. Right now, no one knows how much the insurance will cost, and owners aren't sure if they'd be better off not buying it and paying a government a penalty of $2,000 per worker. Some owners are even threatening to defy the law. The big challenge for most small businesses is that they just don't have enough information to make concrete plans.
If Wang can't afford the insurance, she says that some of her staffers may have to go.
"I would have to say, 'look, guys, you're family to me in many respects, but this family also depends on having the kind of cash flow available to keep the lights on and keep employing most of you,'" Wang says. "It would have to come down to that."
Read the full piece here.
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
