Latest Drugwonks' Blog
They’ve got a list. And they’re checking it twice.
The giant PBM Express Scripts is launching ScreenRx, a program that uses a computer to sift through hundreds of factors that affect patients and forecast who is most likely to forget a refill or simply stop taking their drugs. The company then plans to contact those patients to help them stick with their doctor's orders.
It’s estimated that about $317 billion in additional medical expenses were incurred by the U.S. health care system last year because people didn't comply with prescriptions. These additional expenses might include a heart attack for someone who stops taking cholesterol medicines or an amputation for someone who doesn't adhere to diabetes treatment.
The analysis, called predictive modeling sorts through more than 400 variables that could affect a patient to see which people have enough red flags to warrant concern.
Once a patient has been flagged, they receive a phone call. An Express Scripts representative will talk to the person to see if they need help. The PBM then might send the patient a pillbox if they have a hard time remembering their prescriptions or a special beeper that goes off when it's time to take medicine.
If the patient struggles to pay for the drugs, Express Scripts will provide information on assistance programs.
According to a report in the Washington Post, “Analysts say predictive modeling programs that aim to forecast patient behavior and improve care have been evolving in health care over the past few years, and the Express Scripts product is the latest evolution.”
Survival of the most compliant. Would Darwin have approved?
Eli Lilly’s John Lechleiter believes that the biopharmaceutical industry exists in an “innovation ecosystem.” A new study by the Tufts University Center for the Study of Drug Development (funded by PhRMA) confirms that notion by exploring the breadth and nature of partnerships between biopharmaceutical companies and academic medical centers (AMCs).
The full study can be found here.
The Tufts study examines a subset of public-private partnerships – more than 3,000 grants to AMCs from about 450 biopharmaceutical company sponsors. The Tufts report describes the various types of partnership models that exist, and recent trend as well as identifies next generation academic-industry collaboration models emerging from the public-private-partnership paradigm.
To add to Lechleiter’s phrase, the report discusses the importance for and a model of a sustainable innovation ecosystem. This is in keeping with the ethical and pragmatic policy of the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) regarding the disclosure of conflicts of interest:
“There is no inherent conflict of interest in the working relationships of physicians with industry and government. Rather, there is a commonality of interest that is healthy, desirable, and beneficial. The collaborative relationship among physicians, government, and industry has resulted in many medical advancements and improved health outcomes.”
Some findings from the Tuft’s study:
The partnerships examined in this report fall into three primary categories: joint clinical trials (75%), studies targeting public health priorities (14%), and health research and education projects (11%).
* 72 percent of the joint clinical trials are for pharmaceuticals.
* Studies targeting public health priorities cover a range of topics, including breakthrough-investigations involving multiple disciplines.
* Joint health research and educational activities ranged from basic medicine to translational research to new technologies, particularly nanotechnology and pharmacogenomics.
Tufts found that these relationships often involve company and AMC scientists and other researchers working side-by-side on cutting-edge science with advanced tools and resources, enabling the U.S. to rise to the challenge of various biomedical opportunities, such as personalized medicines and a growing understanding of rare diseases.
The report outlines the 12 primary models of academic-industry collaborations and highlights emerging models, which reflect a shift in the nature of academic-industry relationships toward more risk- and resource-sharing partnerships.
* Unrestricted research support has been one of the most widely used models. While these models have generally represented the most common form of academic-industry collaboration, Tufts research found that they are becoming less frequently used.
* The report found a range of innovative models emerging, from corporate venture capital funds to pre-competitive research centers to increasingly used academic drug discovery centers.
Examples of emerging academic-industry partnership models include:
* The Coalition Against Major Diseases, a consortium under the Critical Path Institute, involves biopharmaceutical companies, academic institutions, and others working together to facilitate the development of effective treatments for Alzheimer’s and Parkinson’s disease.
* Eli Lilly and Company launched the Open Innovation Drug Discovery program to facilitate research on molecules around the world that have the potential to ultimately be developed into medicines by allowing academic and other researchers to submit molecules for free screening as potential drug candidates.
* Sanofi has a strategic alliance agreement with the Massachusetts Institute of Technology’s (MIT’s) Center for Biomedical Innovation focused on advancing knowledge in the area of human health through basic and applied research and promoting scientific exchange between MIT and Sanofi researchers to support the development of health care solutions for patients.
The report highlights the mutual benefits of partnerships:
* Both academia and industry are facing increasingly complex scientific challenges. According to the report, as the scope of some of the scientific challenges is so large, collaboration is viewed as increasingly important to making significant progress.
* Partnerships benefit both industry and academia by providing the opportunity for the leading biomedical researchers in both sectors to work side-by-side to explore the promising new technologies and scientific discoveries that have the potential to treat the most challenging diseases and conditions facing patients today.
The report finds that the nature of collaboration occurs across all aspects of drug discovery. According to Tufts, companies are funding and working collaboratively with the academic component of the public sector on basic research that contributes broadly across the entire spectrum of biomedical R&D, not just for products in their portfolios.
The report concludes that academic-industry partnerships are growing in number and importance as “the translational gap between discovery and clinical development has become increasingly difficult to bridge.” The complementary nature of partnerships involving AMCs and biopharmaceutical companies increases synergies between the two sectors, ―enabling the nation’s R&D enterprise to tackle the most complex and challenging diseases and conditions.
How’s that for sunshine?
The official comment period is over and it's pretty clear that FDA’s February 9th biosimilar draft guidance has sparked resistance among some industry players – specifically over certain definitions and requirements. No surprises there.
Stakeholders sent criticisms over the suggested protocols as well as several recommendations for change. The draft guidance, contained in three documents, represent FDA’s interpretation of the Biologics Price Competition and Innovation (BPCI) Act of 2009.
Biosimilarity
Two drug developers said that the agency should tighten its proposed biosimilarity standards. While commending FDA for “an excellent job drafting guidance on quality considerations for demonstrating biosimilarity to a reference product,” Genentech took issue with FDA’s proposed wording that manufacturers “should” thoroughly assess the analytical similarity of their biosimilars to their reference products, and “should” perform in-depth chemical, physical, and bioactivity comparisons with side-by-side analyses of “an appropriate number of lots of the proposed biosimilar product and the reference product.” FDA also suggested that “where available and appropriate,” manufacturers compare their products with the reference standard for specific suitable attributes such as potency.
The assessment of the analytical similarity of a biosimilar product and the robustness of these methods are fundamental requirements for a biosimilarity assessment, and use of the word “should” implies that it does not necessarily need to be done, Genentech noted. “Please replace ‘should’ with ‘is expected to’ or ‘needs to,’” Genentech stated in a letter transmitted to the agency by Earl Dye, director of technical regulatory policy and strategy.
Novo Nordisk urged FDA to define biosimilars as products that are as similar as scientifically possible to their reference products, at least through sharing the same amino acid sequence, without exception, as their reference products. The company cited FDA’s emphasis on the importance the 3-D structures of proteins play in their biological functions and the ability of post-translational modifications to alter the proteins’ functions.
“FDA should never permit biosimilar applications for products that cannot be adequately characterized,” Novo Nordisk stated in its letter, signed by James C. Shehan, Novo Nordisk’s corporate vp, legal, government, and quality affairs.
Biosimilar producer Biocon counter-suggested that FDA should expect that the expression construct and/or the processing of a proposed product would result in the same primary amino acid sequence as the reference product. Some expression constructs may give a precursor protein that only after modification in the process will yield the same amino acid sequence as that of the reference product, Biocon noted in its letter, submitted by Siriam Akundi Ph.D., associate vp, quality, and regulatory.
Demonstrating Safety
Novo Nordisk also believes that biosimilar applicants “should always submit the results of comparative animal toxicity studies.” It added, “In the current state of science, some form of comparative safety and effectiveness testing will be necessary for almost all biosimilars.
“All biosimilar applicants should conduct at least one comparative clinical pharmacokinetic study and, where there is a relevant pharmacodynamic marker, at least one comparative clinical PD study,” Novo Nordisk added. “Similarly, a biosimilar applicant should always conduct at least one comparative clinical immunogenicity study.”
Two patient groups also called for FDA to promote greater safety. The Colon Cancer Alliance asked FDA to require “extensive” clinical testing of biosimilars, with a system capable of rigorously tracking and tracing them back to their product of origin. “It is critical to the safety of patients that these drugs be submitted to open and robust clinical studies and are marked with a unique and transparent product labeling system that will facilitate robust pharmacovigilance,” Global Healthy Living Foundation (GHLF) president Seth Ginsberg wrote in GHLF’s letter.
Interchangeability
Ginsberg noted that it is difficult to designate a biosimilar as interchangeable with their innovator products unless there is sufficient data. He expressed concern that decisions on interchangeability could be made by pharmacists or insurers through states’ automatic substitution policies. “We believe that the choice of product should be decided only by patients and physicians, who are ultimately responsible for patient care and have the full spectrum of a patient’s medical history,” Ginsberg added.
Novo Nordisk urged FDA to confirm that it would not designate a new biosimilar delivery device or container closure system as interchangeable with its reference product “where additional training on the new device or system is necessary to guide safe use, or where the proposed delivery device or container closure has inequivalent performance or critical design features.”
And miles to go before …
“The keys to success for the biosimilar pathway are informing and educating patients and physicians on the benefits and safety challenges of replicating biologic drugs, providing a unique and distinctive naming and labeling system, and understanding that the FDA’s approval of a biosimilar as a standalone therapy does not mean that it is interchangeable with its biologic counterpart,” the Colon Cancer Alliance stated in its letter to FDA written by CEO Andrew Spiegel.
The alliance urged FDA to adopt a system that uses individual nonproprietary names for biologics and biosimilars, enabling physicians, patients, and regulators to differentiate between products easily—a suggestion also made by Novo Nordisk and the National Association of Chain Drug Stores.
Biocon took issue with FDA’s requirement that sponsors provide “sufficient scientific justification” for extrapolating clinical data to support biosimilarity determinations for each condition of use for which a license is sought. “Once biosimilarity is established, and product is approved for one indication, no additional clinical studies should be expected for obtaining approval for other approved indications,” Biocon stated. “If the route of administration, dosing frequency, and dosage amount of the proposed biosimilar is identical to the reference product for each indication, any additional clinical studies should not be expected.”
Novo Nordisk also urged FDA to publish product-class specific guidance for biosimilar and bioequivalent applications for complex proteins, like the EMA has done. With all the discord that FDA’s draft biosimilar guidance has created, the agency will have to work to balance the interests of innovators, biosimilar developers, and patient groups. The agency will have to ensure that it does not tilt its final guidance toward developers of new drugs by rules that unduly impede biosimilars. Nor should it tilt its requirements toward biosimilar makers seeking less rigorous review. It won’t be easy, but balancing competing interests will ultimately benefit companies, researchers, and especially patients, by finally providing a biosimilar pathway in the U.S.
And that's assuming the law that makes biosimilars possible remains on the books after the Supreme Court ruling.
In Vitro Veritas
A renegotiation of the EMA (European Medicines Agency) medical devices directives is imminent. Our spies tell us that, for in vitro diagnostics, a line will be drawn between tests used as companion diagnostics -- where clinical evidence of their applicability will be required -- and other in vitro tests such as PSA for prostate cancer -- where no such evidence will be required.
Uneasy lies the head that wears a crown
Eric Abadie, the chair of CHMP (The Committee for Medicinal Products for Human Use) has resigned -- another victim of L’Affaire Mediator (the French anti diabetic /anti obesity drug remained questionably available in France and killed somewhere on the order of 5000 patients from pulmonary valve disease). The French Agency sacked him and the EMA opted not to pick up his salary.
Meanwhile on our own placid shores
Here’s an excellent article from the April edition of Nature Biotechnology on some of the key policy questions facing the US biotech sector pending PDUFA and presidential politics.
Part of the FDA’s promise for PDUFA V is a more patient-centered approach to risk/benefit analysis. A timely new analysis provides a closer look at how much cancer patients value hope --with important implications for how insurers value treatment, particularly in end-of-life care.
The analysis by Darius Lakdawalla, director of research at the Schaeffer Center at USC and associate professor in the USC Price School of Public Policy, surveyed 150 cancer patients currently undergoing treatment, and is part of a special issue on cancer spending from the journal Health Affairs.
Lakdawalla and his co-authors found the overwhelming majority of cancer patients prefer riskier treatments that offer the possibility of longer survival over safer treatments: 77 percent of cancer patients said they would rather take a “hopeful gamble” — treatments that offer a 50/50 chance of either adding three years or no additional survival — to “safe bet” treatments that would keep them alive for 18 months, but no longer.
“Consumers tend to dislike risk, and researchers and policy makers have generally assumed that patients care about the average gain in survival,” Lakdawalla said. “But patients facing a fatal disease with relatively short remaining life expectancy may have less to lose and be more willing to swing for the fences. This analysis points to the larger ideal — that value should be defined from the viewpoint of the patient.”
Reaching the wrong conclusion only makes a problem worse. Witness drug shortages and a bill pending in Congress that would require drug manufacturers to notify federal officials of a disruption to a drug supply six months in advance.
In theory, such a requirement would give the FDA an opportunity to prevent the shortage, notify health-care providers and develop a contingency plan. In reality, that’s not the problem.
“What we’re trying to find out is whether there’s a pattern behind the shortages that we can address,” comment senator Richard Durbin (D, IL). “We’ve got to get down to what is really behind it and try to solve it.”
Precisely.
While earlier and more robust communications between drug manufacturers (largely generic manufacturers of hospital injectables) and the FDA is important – lack of such interaction isn’t the major cause of the problem. The issue at hand is that that, because of the way hospitals purchase medicines, there is no incentive for drug makers to update manufacturing facilities or build new ones. Hence, when a facility goes off-line due to quality concerns (the major cause of supply line disruption) or is retooled for a different (and more profitable) use – shortages can occur. In such an instance, should a manufacturer advise the FDA of potential shortages? Certainly.
But that’s not the real problem. The unreported problem is the role of Group Purchasing Organizations (GPOs). GPOs control the purchasing of more than $200 billion in drugs, devices, and healthcare supplies annually for some 5,000 private, acute care hospitals nationwide. And they keep costs low. That’s the good news. The bad news is that they are also permitted (by law) to charge a fee to hospital suppliers based on percentage of sales volume for a particular product. And sometimes it’s a hefty one – often as high as 35-50%. That certainly throws a spanner in the supply-and-demand proposition. Six months supply at ever-lower margins becomes a non-starter for many companies – further exacerbating the problem rather than solving it.
GPOs are a monopsony (a buyer’s monopoly) dominated by six firms that control about 90% of the goods purchased by hospitals via GPOs. The power of these organizations is such that they can often dictate which drugs, devices and supplies are used in hospitals – and which companies are allowed to sell them.
These practices have created a concentrated market that excludes other existing and would-be suppliers and distributors. So, with no other suppliers able or available to fill the gap, increases in demand for generic drugs have resulted in shortages and surging prices. It is no coincidence that the problem is generally limited to generics sold to healthcare facilities through GPO contracts rather than directly to consumers through retail pharmacies.
GPOs have their critics. Among them is former Wall Street Journal reporter Phil Zweig who writes that, “GPOs have concentrated production of generic drugs in a handful of drug makers and have forced some manufacturers to cease production of various lifesaving drugs altogether and distributors to slash inventories to the bone. In a nutshell, these cartels have undermined the laws of supply and demand in this critical industry.”
We applaud Senator Durbin for striving to solve an important problem. We urge him to include not only drug manufacturers and the FDA in potential solutions – but also our nation’s giant Group Purchasing Organizations.
It’s time to actively and aggressively pursue FDA Commissioner Peggy Hamburg’s call for a regulatory Marshall Plan to help build, nation-by-nation, global systems for both quality and safety. A high tide floats all boats.
A new IOM report concludes the FDA should invest in advancing the regulatory capacity of developing low and middle income nations in order to secure the pharmaceutical supply chain and safeguard the American public.
The report, Ensuring Safe Foods and Medical Products Through Stronger Regulatory Systems Abroad, recommends 13 steps FDA and other regulatory bodies can take in the next five years to improve the regulatory systems of developing nations.
Rather than try to inspect all foreign establishments itself—something IOM conceded was unrealistic given FDA’s limited budget—FDA should instead invest in improving other regulatory systems to accomplish its goals of ensuring a safe pharmaceutical supply chain.
After all, as Peggy Hamburg has repeatedly said, ““We can’t inspect our way out of this problem."
The IOM reports, “The FDA should use partnerships to drive improvements in supply chain management. The committee recommends that the FDA work with strong regulators in other countries to plan inspections and pool data. There is no need for American and European inspectors to duplicate each other’s work, especially when a vast number of facilities go uninspected … One promising initiative is the two-year FDA Secure Supply Chain pilot program, which rewards firms that trace their products thoroughly from manufacture to entry into the United States.”
“The report urges FDA and its technologically advanced counterparts in the European Union, Canada, Japan, Norway, Iceland, Switzerland, Australia, and New Zealand to plan a system for mutual recognition of one another's inspections, which would eliminate the wasteful duplication of effort,” wrote IOM in a statement.
FDA, the European Medicines Agency (EMA), Australia’s Therapeutic Goods Administration (TGA) and the World Health Organization have all announced their participation in a global active pharmaceutical ingredient inspection program that might go a long way toward accomplishing IOM’s recommendations—something IOM agrees with in principle.
IOM also called on industry association to “define a reliable way to share internal inspection results among their members within the next three years.
With scare resources, perhaps the best place to start is by committing to common standards for data capture and reporting.
After all, knowledge is power.
It is rare that the words “progress” and “Alzheimer’s Disease” are used (positively) in the same sentence.
Maybe that’s about to change.
Last week the EMA's CHMP adopted a qualification opinion that positive/negative PET imaging of amyloid can be used as a biomarker to identify patients in clinical trials with predementia Alzheimer's disease (AD) who are at increased risk to have an underlying neuropathology. Now an Eli Lilly & Co. diagnostic that detects the presence of proteins in the brain that are related to Alzheimer's disease is FDA-approved.
According to a report in the Wall Street Journal, “The tool could enable clinicians to detect Alzheimer's earlier and more accurately in patients at the earliest sign of memory problems—a potential boon to treatment and developing drugs against the disease.”
A lack of ability to reliably diagnose patients in the early stages of the Alzheimer's disease has hampered research. Some experts believe that investigational drug trials have failed because patients enrolled in such studies already had progressed too far for the treatments to be effective.
Proponents of using florbetapir and similar agents that are being developed have said that such technology will accelerate research by helping to accurately identify people at high risk of developing the condition and to enroll such people in therapeutic trials.
The test uses a chemical called florbetapir, known by the brand name Amyvid, which is a radioactive agent that tags clumps of a sticky substance called an amyloid. Amyloid proteins are hallmarks of Alzheimer's disease. The chemical, which costs $1,600 per dose, then is detected using a brain imaging technique called positron emission tomography, known as PET scans.
The Journal raises an important point, “Some experts have questioned how useful the test is since no treatments are available that significantly alter the course of the disease. But some doctors believe that patients may find a diagnosis helpful for planning purposes or just to know for certain that they have Alzheimer's.”
Question – will payers pay?
If a tree falls in a forest …
BioCentury reports:
EMA backs AD biomarkers
The EMA's CHMP adopted a qualification opinion that positive/negative PET imaging of amyloid can be used as a biomarker to identify patients in clinical trials with predementia Alzheimer's disease (AD) who are at increased risk to have an underlying neuropathology. CHMP also adopted a qualification opinion that the combination of low beta amyloid (1-42) and high tau in cerebrospinal fluid (CSF), and amyloid-related PET imaging, can be used to identify patients with mild to moderate AD who are increased risk of an underlying AD neuropathology. CHMP said the biomarkers are intended to enrich recruitment in trials aimed at studying products to slow the conversion to AD or severe AD.
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.
