Latest Drugwonks' Blog
Per BioCentury, Reps. Fred Upton (R-Mich.) and Diana DeGette (D-Colo.) previewed on Tuesday the goals of legislation they plan to release this month as part of their 21st Century Cures initiative.
In commentary published by CNN, the legislators wrote that their bill will seek to “modernize clinical trials to streamline the approval of drugs and devices,” in part by reducing paperwork and promoting adaptive trials. It will also help FDA “better integrate the patient perspective into the regulatory process,” including using public-private partnerships to strengthen science around biomarkers and patient-reported outcomes.
The bill's sponsors also aim to promote “better access to and sharing of information such as genomic and other clinical data to foster more collaboration among researchers," and to invest in programs for young scientists. Upton -- the chair of the U.S. House's Energy & Commerce Committee -- and DeGette also plan to “incentivize new drugs and devices for unmet medical needs” by “streamlining the premarket process while establishing mechanisms to better capture real world evidence post-market." They also said they will examine incentives, including “exclusivity or simplifying the reimbursement process,” to stimulate the development of new drugs and devices for unmet medical needs.
More as more develops.
The review of Steven Brill’s “What Ails Us” (NYT Book Review, January 11, 2015), refers to the pharmaceutical industry’s back-room negotiations to "gut" comparative effectiveness under Obamacare. The truth is that the Recovery Act of 2009 provided $1.1 billion for patient-centered health research (also known as comparative effectiveness research) – and that’s only part of the story.
What Mr. Brill is actually referring to is the administration’s “deal” with the pharmaceutical industry to leave in place what is known as “the Non-Interference Clause,” which prohibits the Federal government from negotiating drug prices for (among other things) the highly successful Medicare Part D drug program. It’s important to note that the Non-Interference Clause was the brainchild (during the Clinton years) of Senators Tom Daschle and Ted Kennedy – hardly candidates for the Tea Party Hall of Fame.
According to the Congressional Budget Office (in 2004), revoking the Kennedy/Daschle Non-Interference Clause, “would have a negligible effect on federal spending because CBO estimates that substantial savings will be obtained by the private plans and that the Secretary would not be able to negotiate prices that further reduce federal spending to a significant degree. Because they will be at substantial financial risk, private plans will have strong incentives to negotiate price discounts, both to control their own costs in providing the drug benefit and to attract enrollees with low premiums and cost-sharing requirements.”
In 2009 the CBO reiterated its previous views, stating that they, “still believe that granting the Secretary of HHS additional authority to negotiate for lower drug prices would have little, if any, effect on prices for the same reason that my predecessors have explained, which is that…private drug plans are already negotiating drug prices.” Unlike other healthcare benefits, Part D is also cost-effective for taxpayers. In 2014 the CBO reported Part D drug spending was 45 percent below original cost projections.
Importantly, the CBO says that no further savings are possible unless the government restricts beneficiary access to medicines or establishes market-distorting price interventions. In other words, price controls lead to choice controls.
In October 2013, California Governor Jerry Brown vetoed a bill, overwhelmingly passed by state lawmakers that would limit automatic biosimilar substitution to those the FDA deems “interchangeable.” SB 598 also would have required pharmacists to notify physicians when an interchangeable is substituted for a prescribed biologic.
One of the Governor’s stated reasons for his veto was, “The FDA, which has jurisdiction for approving all drugs, has not yet determined what standards will be required for biosimilars to meet the higher threshold of ‘interchangeability.’ Given this fact, to require physician notification at this point strikes me as premature.”
Much has changed since that day – especially per physician notification. Today even the GPhA supports this public health imperative. Perhaps the biggest change in the landscape was yesterday’s ODAC meeting on a biosimilar filgrastim – and not just the overwhelming 14-0 vote in favor, but also the FDA’s strong support of the Sandoz application.
All of a sudden the issues addressed in SB 598 don’t seem so “premature.”
But the filgrastim adcomm isn’t the end of the debate. There are still many issues yet to be determined via FDA guidance (such as nomenclature) and corporate strategy (read, “pricing”). As BIO’s Jim Greenwood said, “This week’s advisory committee meetings facilitated important discussion of the scientific approach of reviewing biosimilar applications and we encourage this positive momentum, however, we believe the appropriate way to develop policy on such a significant new approval pathway is through published guidance documents with the opportunity for public comment, rather than through single-application advisory committee meetings.”
One issue that’s taking a back seat to the approval of biosimilars is the requirement for new thinking on their post-approval safety and surveillance. Biologics aren’t the new kid on the block anymore. While it’s important to pursue ways to expedite 21st century cures (as well as the eponymous legislation), it’s equally important to focus on the details of 21st century follow-on products (both biosimilars and non-biologic complex drugs). Just as the FDA has been diligently pursuing patient-centered drug development, so too must it develop new strategies and tactics (“guidelines”) for patient-centered pharmacovigilance of biosimilars and NBCDs (such as Copaxone).
It’s also time for NORD and all the other patient and disease organizations who were so wonderfully outspoken on the urgency of expediting the FDA review process for new therapies and cures to hoist the banner of follow-on safety.
On pages 21-22 of the FDA briefing documents, an agency analysis found that, statistically, the commercial variety of EP2006 (Sandoz’ biosimilar) was lower in protein content than the comparator product (Neupogen) and was nonequivalent. FDA dismissed this as something that could be worked out with better manufacturing controls and asked Sandoz to correct it. Okay, but isn’t this exactly the kind of thing that can cause “poor responders” to filgrastim to have suboptimal responses? An important fact to consider when debating the value of differential nomenclature for biosimilars.
And then there’s the issue of cost. Many members of Congress have been leaning heavily on the FDA to expedite biosimilar guidances so that payers can realize cost savings.
But what will those savings be?
When ODAC member James Liebmann (assistant professor at the University of Massachusetts Department of Medicine) asked what the price of the Sandoz biosimilar would be, the answer wasn’t a resounding success for those counting their savings before they’re hatched. According to Mark McCamish (Sandoz global head of biopharmaceuticals and oncology injectables development), “We can’t say that the price would be less because in some situations the price will be at parity because of other relative terms that will come into existence that’s there. Price is a relatively complex situation.”
Indeed – as is regulatory science, which is why attention must be paid to creating ever-greater clarity for both biosimilar and NBCD pathways – and in post-approval surveillance.
It’s not just about price – it’s about safety. And it’s not about getting it done fast – it’s about getting it done right. Members of Congress should be focused on greater clarity through guidances because of patient safety issues rather than vague promises of cost-savings. As Brian Harvey (Pfizer’s VP for Regulatory Strategy -- and my former agency colleague) commented, “In lieu of a finalized guidance,” the agency has been making “very good efforts” to provide case-by-case feedback about biosimilars as companies move forward.”
As Brian Harvey (Pfizer’s VP for Regulatory Strategy -- and my former agency colleague) commented, Pfizer has been “very pleased” with the frequency of its interactions with FDA regarding biosimilars and “the granularity of the feedback” the company is receiving.”
For those in the know, that’s great, but it leaves the rest of us guessing. Official guidance would be even better.
Rashid writes: "Muslims today boast, rightfully, about Islam's Golden Age and its unprecedented contributions to the sciences. Muslim leaders worldwide implore Muslims to rise up to that greatness once more. But in doing so, too many ignore the 20th century's most prominent Muslim scientist--one who once again rekindled the brilliance of the countless Muslim scientists who created the Golden Age of Islam."
The source of extremistism is the insistence upon doctrinal certainty and the enforcement of that world view through defilment, descration and death. The refusal to engage in fact-based discussions about the origins of the Universe and the evolution of man means that much of physics and biology is off limits.
In his book "The Ascent of Man" Jacob Bronowski wrote: “There is no absolute knowledge. And those who claim it, whether they are scientists or dogmatists, open the door to tragedy.”
The massacre of this week, the killing of 122 children in Pakistan, the rise in attacks on Jews in Europe are the result of this monstraous centainty. Islamic leaders will be hard put to undermine this aspect of it's epistemoilogy but they must do so to save their religion.
We have not faced a similar assault on freedom since Nazi Germany. And no surpise, the Third Reich rose to power by subsuming science to it's Aryan vision.
Back then the West rose up to defend freedom in the "hour of maximum danger." It must do so now. without apology or resort to the usual relativistic excuses that hamstring the actions and intellectual honesty necessary to that defense. And it can begin by pointing that the gap betweeen Islam and the rest of the world that opens wider with every savage act of violence can be bridged only when the scientific impulse -- the challenge of past dogmas and theories and the dedication to critical thinking -- is wovem into the fabric of education and institutions. Honoring the scientists of today is a good way to demonstrate that necessary shift in outlook.
You can read his article by going to this link: When Will The Muslim World Honor Its First Muslim Scientist Nobel Laureate?
Today, as the FDA’s Oncologic Drug Advisory Committee (ODAC) adcomm debates and discusses whether to recommend approval of a Sandoz filgrastim biosimilar, (supported by the agency in their meeting materials), a few interesting items of note.
On pages 21-22 of the FDA briefing documents, an agency analysis found that, statistically, the commercial variety of EP2006 (Sandoz’ biosimilar) was lower in protein content than the comparator product (Neupogen) and was nonequivalent. FDA dismissed this as something that could be worked out with better manufacturing controls and asked Sandoz to correct it. Okay, but isn’t this exactly the kind of thing that can cause “poor responders” to filgrastim to have suboptimal responses? An important fact to consider when debating the value of differential nomenclature for biosimilars.
Here’s what the FDA had to say …
More concerning was that Sandoz was apparently confused in providing multiple lots of the biosimilar to the FDA for the protein testing. As a result, they thought they had provided 6 lots for testing that turned out to be only 4. Page 4 of the Addendum states:
“On November 25, 2014, Sandoz responded to the Agency request. In the response, Sandoz clarified that the actual number of EP2006 commercial drug product lots used in the statistical analysis referred to above is four lots instead of six lots. The six EP2006 commercial drug product lots initially considered were determined to be not independent because four of those six EP2006 commercial drug product lots were split-fill lots from two EP2006 bulk drug product batches, resulting in only four independent EP2006 commercial drug product lots.”
If Sandoz, a world-class company with a stellar record for cGMPs, in their highly reviewed and internally scrutinized licensing application confuses batches of their biosimilar, what can we expect in the real world after marketing? If Sandoz can’t track different lots of their experimental drug, what will the reality be in the real world? Another cry for sanity in the debate over nomenclature.
Biosimilars are here to stay -- and we need a nomenclature safety net.
A recent article in Biocentury by Roger Longman and Jane Borne of Real Endpoints has some undiluted advice about the challenge drug companies will face getting customers for the record number of new medicines approved in 2014
"HCV has taught payers they can in fact limit access to valuable drugs even when there’s no competition at all. Five years ago, it would
have been unthinkable to deny a relatively healthy but HCV-infected patient a curative drug. Today it’s routine."
Ditto for HIV, MS, psoriasis, various cancers.
"They are willing to challenge head-on, as far as we can see for the first time in a major, potentially fatal disease, the resistance of physicians and patients in order to provide their customers with a mechanism for bending the cost curve in specialty drugs. And that means that we will see similar deals in all significant competitive specialty categories — including in some areas of cancer."
RIght now companies are responding by offering the big pharmacy benefit networks discounts in exchange for being the only drug of it's kind covered. And since the first movers are likely to cut such deals to limit competition, what will happen to other medicines that may have significant benefits for patients or to other medicines that need to be used in combination. When price is the only thing that matters, outcomes take a backseat. And pharmacy plans are doing because, under Obamacare, they can.
Isn't that a restrictive formulary? Won't that kill the other speciality pharmacies and small drug stores that sell on service and not just margin? Isn't that bad for patients?
There's only one right answer: Yes.
There are three things companies must do to get their products to patients. I am not sanguine about the ability or desire of most companies to take these steps.
1. Identify groups of patients that benefit most from a new medicine, especially groups that will benefit and require a combination of treatments to improve health.
2. Demonstrate the benefit of such treatments to patients and their families in terms of a return to or continuation of life free for disease. Estimate the value of this state of wellness and estimate the cost -- in terms of out of pocket spending, lost productivity and even death -- of forcing people to use a drug that's cheaper for a health plan but not best for a patient.
3. Demonstrate the benefit of such treatments to employers, universities, retirement funds, life and disability insurers, Medicare, Social Security. And share this information widely and with Congress. Otherwise valuable Obamacare reforms to eliminate discrimination against chronically ill people through restrictive formularies will fail.
As Longman and Borne note: It’s crucial that biopharma provide (these other stakeholders) the appropriate measurement tools. If they don’t, buyers will settle on the easiest point of comparison: price.
From
And Ivan Ackerman. Always the wrong answer. Always.
According to Inside Health Policy, an American Medical Association internal council report reveals the group is leaning toward a naming scheme where biosimilars and their reference products would share the same International Nonproprietary Names (INN). The report says that unique names may suggest different active ingredients within the products and go against standard nomenclature. This stance differs from that of the innovator biologics industry and a handful of specialty physician groups, which argue that shared naming would improperly imply interchangeability.
Wrong.
Assigning differential naming to biosimilar products will certainly prove challenging to the various constituents of the drug compendia community — but it will be crucial for pharmacovigilance. In the real world, how can we not have separate names when there are going to be four categories of products?
Based on comparative analytical data, FDA will characterize its assessment of biosimilarity into one of four levels -- not similar, similar, highly similar or highly similar with a fingerprint-like similarity — depending on the type, nature and extent of any structural and functional differences revealed.
Additional pharmacologic studies would be required to show that the identified difference is “within an acceptable range to consider the proposed biosimilar product to be highly similar to the reference product.”
FDA said only products in the top two tiers would meet the statutory requirement for analytical similarity under the Biologics Price Competition and Innovation Act of 2009. Products in the top two tiers would then only require “targeted and selective animal and/or clinical studies to resolve residual uncertainties” to demonstrate biosimilarity. In addition, these data could be used to extrapolate clinical data for additional indications.
The argument that differential naming is bad for patient safety is pure Orwellian Newspeak — specifically “blackwhite, ” The ability to accept whatever “truth” the party puts out, no matter how absurd it may be — no matter the lack of supporting data. When it comes to biosimilar nomenclature, it’s urgent that we keep our priorities straight. And that means keeping patient safety, not interoperability challenges, at the top of the agenda. Fortunately, White Oak trumps blackwhite.
The good news is that a handful of specialty physician groups disagree with the AMA and are siding with the innovator biologics industry in urging FDA to adopt a biosimilar naming scheme under which products have distinguishable names, pushing back against arguments made by an American Medical Association council and generic drug makers for shared International Nonproprietary Names (INNs). The groups, like innovator companies, argue that distinct names are needed to track adverse events and to protect against improper pharmacy substitution.
The specialty physician groups wrote to FDA on December 18th that a shared name would imply interchangeability, referencing statements made by the agency in past about how INNs should not be used to "imply pharmacologic interchangeability of products with the same active ingredient(s)."
Signers of a the letter include: Alliance for Patient Access; American Academy of Allergy, Asthma & Immunology; American Association of Clinical Endocrinologists; American College of Rheumatology; American Gastroenterological Association; Association of Black Cardiologists; American Urological Association; Clinical Immunology Society; Coalition of State Rheumatology Organizations; physician co-conveners Biologics Prescribers Collaborative; and members of the National Physicians Biologics Working Group of the Alliance for Patient Access.
For a more complete debunking of the AMA’s position, see the recent FDLI paper, Biosimilar Nomenclature: Can we Achieve the Truth, the Whole Truth, and Nothing but the Truth?
Claude Debussy said, ‘‘Music is between the notes.’’ And the same can be said for biosimilarity and the practice of medicine. We now have many thoughtful guidance documents but, in many respects, it’s just theory. And just as the case with music theory, the words on the page are one thing—but when talented performers sit down at different pianos in disparate venues the results are both similar and unique.
In particular AHIP, the AHIP funded sock puppet called the National Coalition on Health Care and Express Scripts have been feeding the media beasts scare stories of greedy Big Pharma and their high prices forcing health systems to ration care. In the wake of all the new drug approvals (and the FDA is still too damn slow) anticipate the next wave of articles about "How Can We Afford All These Drugs?"
The fact is, new medicines are developed not to save health plans money. They do by replacing sick hospitalizaed patients with healthy productive comsumers and premium payers. But new medicines -- especially this generation of drugs and the next -- are developed to predict, and prevent diseases from progressing by using what Eric Topol and Stephen Quake called molecluar stethoscopes: chips and high powered computers that can detect and sequence the gene expression networks impllicated in disease or disease risk in real time. That will lead to more precise answers about how to prevent and how to treat disease. And it will lead to an acceleration of drug development and to determining with nearly 100 percent accuracy what works.
The AHIPs and Express Scripts of the world, as well as most hospitals (at least in the US) are seeing their business model crumble. They don't know it yet, anymore than the record companies and movie chains and department stores had the foresight to anticipate how digitization of information would force them to the brink of extinction. It's happening to the big box approach to health care. And the rent seekers and businesses that will be destroyed are panicking.
The only ways they have left to defend the status quo is lobbying, regulations and scaring the public. And they will fight like hell to limit access to new, targeted treatments that deliver most of the economic and social benefits to indivudals. WIth a willing and biased media behind them, they will have some initial success. But soon the winds of change will sweep them and their pre-industrial approach to managing care will away.
We are on the edge of the Cure Century and they hate it.
In case you missed this story over the holidays.
WASHINGTON (AP) -- The Food and Drug Administration approved 41 first-of-a-kind drugs in 2014, including a record number of medicines for rare diseases, pushing the agency's annual tally of drug approvals to its highest level in 18 years. FDA drug approvals are considered a barometer of industry innovation and the federal government's efficiency in reviewing new therapies. Last year's total was the most since the all-time high of 53 drugs approved in 1996.
The 2014 approval list includes 15 drugs for so-called orphan diseases, which are rare conditions and disorders that affect fewer than 200,000 people in the U.S. Last year's tally, which included drugs for rare cancer and metabolic disorders, exceeded the 13 orphan drugs approved in 2012.
Nine drug approvals in 2014 benefited from the FDA's "breakthrough" designation, a recent program designed to speed up development of promising drugs by providing companies with extra meetings and earlier communication with FDA scientists. Milne said these meetings provide more predictability and transparency about the FDA review process, a boon to both companies and investors.
The complete AP story can be found here.
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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.
