Latest Drugwonks' Blog
www.sciencemag.org/content/333/6047/1216.summary
www.biocenturytv.com/fullplayer.aspx#/BC+Show+52%3A+Biodefense/BioCentury+09.11.11+-+[3]+10+Years+After/608459720001/1150255534001/1153307594001
The need for a commercial application of products is critical to making the nation safer. The government drains value from bio-defense, it does not create it.
Nature Biotechnology opines on BIO’s proposal for a renewing and revitalizing the FDA:
Keeping innovation on American soil may also prove a Sisyphean task. BIO states that in 2009, 35% of pharma companies outsourced to Asia, primarily China and India, and almost a third of small US biotech firms have been tapped to move their R&D operations abroad of biochemical, genomic, imaging, metabolite, cellular, physiological and clinical scoring-scale information gathered from clinical trial reports, scientific conferences and public literature.
The complete article can be found here.
When I was at the FDA, we made a conscious effort to stop referring to “compassionate use” because it made it sound like “noblesse oblige.” We began to call it what it should be – expanded access.
In a house editorial, the New York Times misses the mark not only on this point (where they refer to “humanitarian use” – a nonsensical misnomer), but also as it relates to “comparative effectiveness.”
The Gray Lady opines, “This case raises the question of whether the F.D.A. should demand more rigorous trials before a device is granted a humanitarian exemption. It clearly shows the value of conducting rigorous controlled studies with enough patients to provide meaningful results. This is just the kind of comparative effectiveness research that the national health care reforms seek to promote.”
Well, yes and no.
Sure, the FDA should always strive to better understand where expanded access programs may lead. (And, it’s important to note, many patient groups – such as the Abigail Alliance – believe the FDA is already too slow and stingy with such protocols.) But even the best folks at the FDA are only so prescient. I think it wise to give the folks at White Oak the benefit of the doubt. Adoption of the Precautionary Principle (where nothing is done until everything is known) only leads to nothing being done and the death of innovation.
And as far as the “comparative effectiveness” statement is concerned, this situation has nothing to do with it whatsoever. A larger scale trial of these stents uncovered the safety problem -- precisely what such trials are designed to do. It has nothing to do with "comparative effectiveness." When it comes to the FDA -- it's about safety and efficacy.
But when you’ve got a hammer, every problem looks like a nail.
First it was gun slinging against Forest Labs, now the HHS OIG is gunning for price controls.
According to BioCentury, the OIG has recommended that the Obama administration seek authority from Congress to more effectively control Part B drug and biological expenditures. The recommendation came in a report released Wednesday documenting the difference in acquisition cost for Lucentis ranibizumab from Genentech Inc. for wet age-related macular degeneration and Genentech's Avastin bevacizumab, which is used off-label in the indication as a cheaper alternative.
The report said using Avastin instead of Lucentis for wet AMD would have saved Medicare Part B $1.1 billion and beneficiaries $275 million in copayments in 2008-09. In those years, HHS OIG said the average sales price for a dose of Lucentis, a mAb fragment against VEGF-A, was about $1,915 compared to about $7 for an intravitreal dose of cancer drug Avastin, a humanized mAb against VEGF.
The report noted that CMS, which reimburses for both drugs for AMD, does not have the authority to require price concessions or rebates for products covered under Part B. In a written response including in the report, CMS said it is "evaluating our current authorities and will seek additional authorities as necessary."
Genentech said in a statement it will not comment until it finishes reviewing the report. The company added "we do not believe that cost should be the only factor considered when choosing a medicine."
In fact, he made the most sense science-wise of all the candidates.
1. He did not back down on the need or requirement to have children receive a vaccine that can eliminate many forms of cancer. I thought it was a courageous and principled stand when he first called for HPV immunizations for all 12 year old girls. By contrast other presidential candidates -- Bachman, Santorum and Ron Paul in particular -- seem to suggest that parental rights trump immunization requirements in every case. If that is so, then we need to ask these candidates if they oppose immunization requirements for children and if they believe vaccines cause autism. Then we will see who is anti-science.
2. Perry did more to advance medical science in Texas than other governors running for President have done. Not only did he lead in the establishment of Cancer Prevention and Research Institute of Texas (CPRIT), a $3 billion, 10-year cancer research fund, Texas in one. Just recently CPRIT recruited a leading stem cell researcher to establish a pediatric cancer initiative at University of Texas (UT) Southwestern Medical Center at Dallas. The researcher, Sean Morrison, said this about Texas:
While I have been spending the last five to six years arguing with the Legislature about what kind of research would be permitted in the state, in Texas they were looking for ways to invest billions of dollars into medical research..."Texas is clearly an environment that's more supportive generally of research innovation. Three billion [dollars] for cancer research is going to change the landscape."
PS. Perry has never supported proposals to ban stem cell research in Texas either.
Ignoring these aspects of Governor Perry's record while questioning his position that the 'science' behind predictions of global disaster and requires massive government intervention in the economy -- which is what the debate is all about -- is anti-science is simply a tactic to silence that individual. Or make him or her look stupid.
I still would like to know if the candidates who criticized Perry are opposed to mandatory vaccination in any case.
"We spent as much money as we could, and got as little for it as people could make up their minds to give us. We were always more or less miserable, and most of our acquaintance were in the same condition.” -- Great Expectations
In terms of “learning” about healthcare reform from our British cousins, here’s lesson #1: Don’t believe everything (or anything) you heard on SiCKO. Lesson #2 is seeing CMS Administrator Dr. Donald Berwick in the role of Pip.
According to an investigation in the Daily Telegraph, at least 10 primary care trusts (PCTs) have told hospitals to increase the length of time before they see patients in order to save money.
In one case a manager said the policy keeps patients in line as “short waiting times also create more demand for treatment due to the expectations this raises."
In some areas, patients endured delays of 12 or 15 weeks after GPs decided they needed surgery, even though hospitals could have seen them sooner.
The maximum permitted time between referral and treatment is 18 weeks.
It comes after an NHS watchdog suggested that if patients are forced to wait a long time, they will remove themselves from lists “either by dying or by paying for their own treatment."
Andrew Lansley, the Health Secretary, said: “This practice is simply unacceptable and one of the many reasons we need to modernise the NHS and put patients’ interests first.
The complete article from The Telegraph can be found here.
“Pause you who read this, and think for a moment of the long chain of iron or gold, of thorns or flowers, that would never have bound you, but for the formation of the first link on one memorable day." -- Great Expectations
Hat tip to Helen Evans at Nurses for Reform.
A sudden bold and unexpected question doth many times surprise a man and lay him open. – Francis Bacon
The official PDUFA V technical letter contains no surprises. There are no “Christmas Tree items.” It is a document full of incremental improvements. It is, in a word, “clean.” But don’t let that fool you. There’s a battle ahead.
(The technical letter can be found here.)
Unlike past reauthorization, when industry and agency reached agreement and Congress rubber-stamped it, this year there are going to be questions. Some relevant (predictability and responsibility), some not (greater regulation of consumer marketing practices), some thorny (should biosimilar reviews be covered under PDUFA through fiscal year 2017). It’s a long list.
For many involved in the reauthorization process, one statement that keeps coming up is -- ”The FDA is broken.” But what does that mean? Rather than making blanket statements that cause friction and promote areas of disagreement, one thing everyone can agree to is that the FDA’s must be both ally and accelerator in the advancement of innovation.
Can that be accomplished within the confines of PDUFA V?
PDUFA IV expires Sept. 30, 2012. Senator Tom Harkin (D, IA -- Chairman of the Health, Education, Labor and Pensions Committee) said he hopes PDUFA V will reach Congress by year-end, so that his committee can mark up the legislation in the spring. Representative Joe Pitts (R, PA -- Chairman of the House Energy and Commerce Committee's health subcommittee.) said he hopes to have PDUFA V enacted by June 30, 2012.
Let the battle begin.
For another interesting view on the “deal on the table,” have a look at what Robert Metcalf, Vice President, Global Regulatory Affairs at Eli Lilly & Company, has to say. His comments can be found here.
Life imitates art. In Franz Kafka’s unfinished story, “The Trial,” a man is arrested and prosecuted by a remote, inaccessible authority, with the nature of his crime revealed neither to him nor the reader.
Well – it’s déjà vu all over again -- new Russian regulations making it harder for the Rodina to become an international destination center for clinical trial excellence. And nobody knows why.
As Dr. Meir Pugatch discusses in a new Journal of Commercial Biotechnology article, “The overall, the strength of national pharmaceutical IP environments provide a good estimate of the level of clinical trials taking place in these countries. Accordingly, countries with a more robust level of pharmaceutical IP protection tend to enjoy a greater level of clinical trial activity by multinational research-based companies. In other words, by choosing to improve their level of protection of pharmaceutical IPRs (together with other factors), developing countries may also be exposed to higher levels of biomedical FDI, not least in the field of clinical trials.”
(More on Dr. Pugatch’s article can be found here.)
This is bad news for Russia.
New data shows that clinical trial activity in Russia is still on the decline following the introduction of new regulations last year. The total number of trials approved in the first half of 2011 fell by 36% to just 200, with trials conducted locally by domestic sponsors most affected, falling by around 80%, according to the Russian clinical trials organization, ACTO.
The slowdown is mainly due to the law on circulation of medicines, which came into effect in September last year. Among other things, the law incorporated local clinical trials into the drug registration process, introduced new trial approval and insurance procedures, and imposed a ban on the import of registered products for use in clinical trials.
Not only is this bad news for international investment – but it also has the unfortunate side effects of making it more difficult for Russian companies to conduct clinical trials in their own country. Russian companies wanting to conduct local trials (as opposed to Russian arms of multinational studies) can do so only as part of a drug registration procedure, not as freestanding studies.
According to ACTO Executive Director Svetlana Zavidova, she did not know why this distinction had been made, but it was possible that those drafting the law had simply forgotten to state that local clinical trials were also a freestanding kind of study.
Kafkaesque – and with unfortunate results.
The number of local safety and efficacy studies approved in Russia fell by 78.4% to 19 in the first half of 2011, while bioequivalence studies were down by 84.4% to just seven. According to ACTO, the fall in bioequivalence studies is probably due to two factors: there are no approved requirements for such studies, and in some cases generic manufacturers cannot refer to the originator's pre-clinical trial results and are having to carry out their own tests, thereby delaying the bioequivalence study.
These developments are somewhat worrying given that the government has made much of its plans to build up the Russian pharmaceutical industry and reduce the country's reliance on imported medicines. "It is remarkable that the implementation of the law had a particularly tough impact specifically on the innovation activity of Russian companies, which is in direct contradiction with the governmental desire for import substitution in pharmaceuticals," ACTO commented.
“Remarkable?” Not really. Predictable? Absolutely.
On the positive side, sponsors of international trials fared better than their Russian counterparts in the first half of 2011, gaining 163 trial approvals compared with 160 in the 2010 period. Nonetheless, they had their own problems, including the lack of new rules on insurance, which should have been in place on 1 January this year, and the ban on importing registered drugs (for use as comparators in clinical trials of experimental drugs).
Bad News: The import ban affected not only new studies but also those already under way where stocks of the approved drug were running short, says ACTO, which notes that some new studies were cancelled and transferred to other countries.
Good News: The ban was finally lifted in June this year when the health ministry took over responsibility for the importation of both approved and unapproved medicines, while the insurance question was dealt with by a May decree implementing the amended rules.
Bad News: Another factor dampening trial activity has been the fact that the authorities are not adhering to the new, shorter timeframes for trial approvals stipulated in the new law.
In fact, according to ACTO, things are even worse than they were before the law came into force: in the first six months of 2011, the total time taken to gain approval for a trial and obtain import/export permits amounted to an average of 160 days. This is "twice as long as the maximum period allowed by law and 30.5% longer than the all-time worst results.”
Other problems remain, says ACTO, including the fact that foreign companies still have to conduct a local trial (free-standing or as part of an IMCT) when seeking new drug registration in Russia. "Unfortunately, this problem is still on the front burner for us", ACTO’s Zavidova commented.
That must be some big front burner.
Considering the importance of clinical trials as a leading indicator of international pharmaceutical investment, perhaps Moscow should seek expert advice on the subject. After all, as the Russian proverb says, “With a helper a thousand things are possible.”
Is 4% a lot or a little? Well – it depends whether you’re one of the 4%.
As the AP reports, “Pfizer Inc.'s just-approved drug Xalkori, the first new medicine in more than six years for deadly lung cancer, proves the value of precisely targeting rare diseases linked to gene variants
The drug was approved Friday in the U.S. along with a companion diagnostic test for just a small subset of lung cancer patients. It is the poster-child for the 21st century strategy of developing medicines for relatively few patients to replace (as the AP puts it) “blockbusters for the masses.”
"This is a paradigm shift," Dr. Paul A. Bunn Jr., a University of Colorado professor and cancer researcher involved in testing Xalkori, told journalists during a conference call hosted by Pfizer. "It used to be that everybody with cancer was treated the same," with surgery and chemotherapy.
Xalkori, a pill with relatively minor side effects compared to the hair loss and nausea that chemotherapy can cause, was approved for the roughly 4 percent of patients with advanced nonsmall cell lung cancer who have what's called the ALK fusion gene.
About 6,000 Americans a year develop this cancer, Pfizer said. Those patients, called ALK positive, now can be identified with a $250 molecular diagnostic test developed by Pfizer's partner, Abbott Molecular Oncology. The test was also approved Friday.
According to Dr. Mark Kris, head of the thoracic oncology service at Memorial Sloan-Kettering Cancer Center in New York, "You're going to be sparing individuals side effects (and) the waste of resources, time and drug that really isn't going to help them."
Cost efficient and patient-centric. Bingo.
Personalized medicine, targeted therapy – call it what you will. It’s real. And it’s a giant step towards achieving the 4 rights – the right medicine in the right dose for the right patient at the right time.
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.
