Archive for the ‘FDA’ Category

Capitalizing on the Promise of Precision Medicine

January 23, 2015

The Personalized Medicine Coalition (PMC) is pleased that the President has announced the launch of a new Precision Medicine Initiative during his State of the Union Address. Personalized medicine exemplifies the potential of emerging science to improve patient outcomes and support efficient health delivery. We hope that this new effort will renew focus on policies that can help accelerate advances in targeted treatment, all the way from discovery though delivery.

As President Obama said during Tuesday night’s address, personalized medicine has reversed diseases once thought to be unstoppable and as a nation, we need to do more to harness the benefits of such innovative treatment advances.  The President stated, “I want the country that eliminated polio and mapped the human genome to lead a new era of medicine — one that delivers the right treatment at the right time.”

In order to reap the rewards of our federal investment in the human genome, innovative reforms will be necessary throughout the development process – all the way from discovery through delivery and payment for health care. Focusing on any one aspect of this complicated continuum is not enough. We have worked with stakeholders to identify policies that will accelerate these advances such as increased coordination across FDA in the review of personalized medicine products, appropriate reimbursement for the diagnostic tests that enable the use of targeted therapies and incentives for their development.

PMC has been working to secure these reforms and more in Congress through the bi-partisan 21st Century Cures Initiative and with the broader personalized medicine community to educate key stakeholders about the advances in science that are leading us to this new era in medicine. We look forward to working with both the Administration and Congress to accelerate innovation in support of better patient care, and deliver on the promise of personalized medicine.

Required Reading: September 2014

September 26, 2014

Great stories are published daily about the impact personalized medicine is having on individual patients, and the medical community as a whole, but it can be a challenge to stay on top of the news. With that in mind, we bring to you a monthly roundup of the three to five most thought-provoking articles we are reading, sharing and discussing with our colleagues.

This is the September 2014 installment of Required Reading.

Medical Calculators Use Big Data to Help Patients Make Choices by Laura Landro, The Wall Street Journal

Michael Kattan, chairman of the department of quantitative health sciences at Cleveland Clinic’s Lerner Research Institute, discusses sophisticated risk calculators, or “nomograms,” that can combine a patient’s unique characteristics, such as age, gender, race, extent and type of disease and other health factors; compare them with the vast databases of similar cases and studies; and use them to predict probable outcomes depending on the treatment a patient chooses.

FDA’s Shuren Defends Plan to Issue Guidance for LDTs at House Hearing by Michael D. Williamson, Bloomberg BNA

On September 9, the House Energy and Commerce Committee’s Subcommittee on Health held a hearing to examine the regulation of laboratory developed tests (LDTs) as a continuation of the committee’s 21st Century Cures initiative. Members heard testimonies from various witnesses on recently released guidance from the U.S. Food and Drug Administration (FDA) and its impact on innovation and the practice of precision medicine. Read more about the FDA’s proposed framework for regulating LDTs.

Experts Warn US in Danger of Losing Biotechnology Edge by Chris Casey, Medical Xpress

The United States is in potential danger of losing its biomedical edge to countries that are aggressively funding research into personalized medicine, according to discussion that emerged at the 21st Century Cures Roundtable on September 5. Roundtable panelists noted that biotechnology is at a crossroads in America, and that funding levels for research have flattened in recent years.

Researcher Urges Wider Genetic Screening for Breast Cancer by Rob Stein, NPR Shots Blog

Mary-Claire King, the geneticist who identified the first breast cancer gene, is recommending that all women get tested for genetic mutations that can cause breast cancer, regardless of their personal or family history. According to a paper she recently published in Proceedings of the National Academy of Science, women who carry mutations in BRCA1 or BRCA2, but have no family history of breast or ovarian cancer, have the same high risks of developing either cancer as those who are identified to be at-risk by virtue of their family history.

FDA Outlines Personalized Medicine Policy with Publication of LDT Draft Guidance Document, Final Guidance on Companion Diagnostics

August 15, 2014

On July 31, FDA announced drastic changes to regulation for personalized medicine products and services when it coupled the release of the long-awaited final guidance document on the regulation of companion diagnostic devices with a proposed framework for regulating laboratory developed tests (LDTs), which was also long-awaited or long-feared, depending on your perspective.

The final guidance on In Vitro Companion Diagnostic Devices was welcomed by the personalized medicine community because in the document, FDA clarified the path for co-developed drug-diagnostic products, and finalized their assertion that new targeted therapeutics will not be kept from the market if the diagnostic kit is not ready at the same time. This enables promising new drugs to come to market while also allowing the laboratory community to fill testing needs in cases where an FDA-approved kit is not available for therapeutic selection, dosing and avoidance decisions.

However, many issues remain to be addressed.

To address concerns that FDA regulation will pose obstacles to an already challenged laboratory industry, there is a rather long transition phase — nine years — and an initial focus on high-risk. FDA defines high-risk LDTs as those with the same intended use as cleared or approved companion diagnostics, LDTs with the same intended use as an FDA-approved Class III medical device, and certain LDTs for determining the safety and efficacy of blood or blood products. This focus and transition period will allow clinical laboratories and FDA time to adjust. By focusing initial regulation on high-risk LDTs, FDA makes a strong argument for the framework, and slices off a rather small segment of the LDT market.

Many have argued that FDA does not have the bandwidth to regulate LDTs. FDA responded to this claim by reiterating enforcement discretion for the vast majority of LDTs and outlining a process for LDT regulation, which might be less onerous than traditional regulatory pathways for medical devices.

Although FDA made great efforts to address concerns about the Agency’s new regulatory enforcement, it did not address perceived conflicts between laboratory regulation under Clinical Laboratory Improvement Amendments (CLIA) and this new framework. Furthermore, FDA intends to use an expert advisory panel to provide recommendations to the Agency on LDTs risks and classification on certain categories of LDTs, as appropriate. I suspect that defining those categories will be contentious and, at times, difficult.

Investors have long argued that clarity is necessary in both regulation and reimbursement for continued advancement of personalized medicine. We now have clarity on FDA’s current thinking although many issues remain unresolved. The community has time to consider this framework and may soon have a chance to provide public comments. And finally, the pharmaceutical industry has the FDA’s assurance that targeted treatments will not be held up by co-development challenges.

BREAKING NEWS: FDA Notifies Congress of its Intent to Publish Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs)

July 31, 2014

Summers in D.C. are notoriously slow. FDA, however, has added excitement to this summer by informing Congress of its intent to publish a long-awaited framework for LDT regulation.

In its notice to Congress, FDA included what appears to be a draft of the document. After the mandatory 60-day Congressional review, the draft guidance document will be formally issued for public comment.

Within the draft framework, FDA proposes a risk-based, phased system of oversight. They recognize community concerns around access and do not intend to interrupt the marketing and sale of currently available tests. Furthermore, FDA expresses the intent to continue using enforcement discretion for forensic and organ transplantation uses, traditional LDTs, and LDTs for unmet needs.

The document outlines the history of LDT regulation, FDA’s policy of enforcement discretion, and how personalized medicine has caused FDA to reconsider that policy.

We will continue to provide updates on the development of framework for regulatory oversight of LDTs, with additional in-depth commentary next week on this issue and the related news of FDA’s final guidance on companion diagnostics.

For additional information on the current regulation of LDTs, please read PMC’s report “Pathways for Oversight of Diagnostics.”

Sustaining Progress in Personalized Medicine

December 4, 2012

Last week, I had the opportunity to speak at the Harvard Personalized Medicine Conference in Boston, MA. No other conference on personalized medicine brings together the array of scientists, stakeholders, and experts that this event does. This year the conference drove home to me that the potential to improve patient care via personalized medicine is greater than ever – yet the scientific and clinical challenges remain daunting. It is more important than ever to sustain biomedical innovation, and to ensure that health policy is informed by the enormous opportunity, and complexity, of making continued progress in this field.

The event also underscored that biopharmaceutical research companies are deeply committed to advancing the science of personalized medicine and building it into their research and development strategies. It affirms findings of a report released by the Tufts Center for the Study of Drug Development in 2010 which found that 94% of biopharmaceutical companies surveyed are investing in personalized medicine and 100% are using biomarkers in the discovery stage to learn about compounds. This research has required large up-front investments in new research tools and training. But, as we have seen in the last year-and-a-half with FDA approval of new targeted therapies for lung cancer, melanoma, and cystic fibrosis, it is starting to bear fruit for patients.

I’m hopeful we’ll see more approvals in the months ahead. In the report from Tufts, companies reported that 12-50% of compounds being researched are personalized medicines and over the last five years, they have seen a roughly 75% increase in their investment in personalized medicines. The importance of personalized medicine was illustrated in the reauthorization of the Prescription Drug User Fee Act, which provides FDA with increased resources and staffing to advance the regulatory science in areas such as pharmacogenomics and biomarkers.

This progress, however, doesn’t happen in isolation. The Harvard Conference participants represented, and illustrated, the wide range of organizations and individuals from different sectors that make up the research ecosystem that drives progress in personalized medicine. As the science of personalized medicine advances, research partnerships and collaborations will be more important than ever. To sustain progress in personalized medicine, it is vitally important to ensure that policy and regulation do not erect barriers to these types of partnerships.

Biomedical innovations like personalized medicine will help address major unmet medical needs, and offer a solution to rising healthcare costs.  As we face continued pressure to contain healthcare costs, it is crucial to ensure that healthcare policy sustains the innovation ecosystem and incentivizes continued progress in personalized medicine.

Approaching One-Year Anniversary at FDA, Stephen Spielberg Highlights Agency’s Progress in Personalized Medicine

August 20, 2012

In his address to the Personalized Medicine Coalition (PMC) Policy Committee at our most recent meeting, Stephen Spielberg, M.D., Ph.D., Deputy Commissioner for Medical Products and Tobacco at the U.S. Food and Drug Administration (FDA), announced that the Agency will develop a catalog of personalized medicine-related activities. The catalog, as Dr. Spielberg described, will provide a full accounting of the activities at the agency, including all regulatory divisions and regulatory science.

While reflecting on his 11-month tenure at the agency, Dr. Spielberg also noted that the largest area for advancing personalized medicine was through communication among stakeholders and FDA Centers.  He noted that “PMC is so important because we need dialogue; no one has a lock on complete information.”

The attendees of the policy meeting were pleased to hear that already, less than a year into Dr. Spielberg’s appointment at the agency, he was working to encourage collaboration and communication across divisions.  Dr. Spielberg was previously Director of the Center for Personalized Medicine and Therapeutic Innovation at Children’s Mercy Hospital, one of the founding members of the PMC and so has experience in bringing groups together to advance personalized medicine.

Dr. Spielberg outlined his optimism for personalized medicine at the FDA, noting that one third of the new drug approvals currently in review are for targeted or orphan indications.  He said that by year’s end, we could expect guidance documents on companion diagnostics and co-development, as well as the previously mentioned catalog.

These guidance documents and a FDA catalog may prove to be additional stepping stones to a broader understanding of the impact of personalized medicine on scientific research and clinical medicine.  At PMC, we will continue to work with FDA to promote broader engagement across the ecosystem of stakeholders and greater transparency around research and drug development.  We look forward to the issuance of these materials later this year and will engage a public discourse about them.

National Bioeconomy Blueprint Showcases Personalized Medicine as Model for Strengthening U.S. Bioeconomy

May 7, 2012

Last week, the White House released its National Bioeconomy Blueprint.  It lays out some strategic objectives designed to help realize the full potential of the U.S. biotechnology sector to generate economic growth by creating jobs and addressing societal needs.

As an example of how the government’s efforts can facilitate the development of a more robust bioeconomy, the report discusses the impact of the Human Genome Project and the development of personalized medicine. The Blueprint cites the Case for Personalized Medicine, 3rd Edition, noting “advances in recent technologies have increased the momentum of personalized medicine – customized healthcare based on specific genetic or other information of an individual patient.”

While we agree that policies are needed to help support research and development (R&D), improve translational and regulatory science, improve regulation in other areas, enhance workforce training, and develop new public-private partnerships and precompetitive collaborations, we are concerned they are not sufficient to allow us to realize Adriana Jenkins’ dying wish, that all patients have access to personalized treatments.

The White House is correct to shine a light on FDA and direct the agency to focus attention on application review times, coordinated parallel reviews of products, and continued improvement of regulatory science. In reality, we are already seeing the benefits of this increased coordination – with FDA’s accelerated review and approval of Kalydeco™ for cystic fibrosis and Xalkori® for non-small cell lung cancer, each with a companion diagnostic approved together and in advance of FDA time lines.

Still, engaging on regulatory science and streamlining FDA processes will only go so far to improve the bioeconomy and bring personalized medicine to patients. For instance, current comparative effectiveness research (CER) and health technology assessment (HTA) models, which are not addressed in the Blueprint, are not well aligned with the science of personalized medicine and such misalignment causes additional barriers to market entry and patient access after FDA approval. The Blueprint highlights coverage with evidence development (CED) as a potential HTA model, but it should be noted that although CED can be a good tool, if done wrong, it can also chill innovation.

Likewise, unclear and unrealistic expectations for obtaining Medicare coverage and adequate payment for personalized medicine products and services are a substantial hurdle, preventing companies from seizing the full scientific potential and translating that into new treatments and the resulting high-paying jobs and economic contributions that follow.

We look forward to working with the Administration and with Congress to shape policies that will help support the ability of companies to continue to develop personalized medicines and bring them to patients, including research and development tax credits, delivery system reforms, and regulatory and reimbursement policies. Given the tremendous potential of personalized medicines, it’s key that we get the policies right to foster companies working on personalized medicine and thereby improve patients’ lives and our economy.

The Genomics and Personalized Medicine Act Needs a “Fresh Look”

October 11, 2011

Now is the time for a national effort to move personalized medicine forward,” said Representative Anna Eshoo at the Center for the Study of the Presidency and Congress and Health Affairs’ Capitol Hill briefing held last week, on the same day that the Food and Drug Administration (FDA) released its plan Driving Biomedical Innovation:  Initiatives for Improving Products for Patients.

At the briefing, Congresswoman Eshoo affirmed the Personalized Medicine Coalition’s long-held contention that the 2010 version of the Genomics and Personalized Medicine Act needed an infusion of new ideas.  (See my blog post from August 23, 2011.)

Also speaking to the audience of congressional staff, reporters, patient advocates industry representatives, and others, were several government officials tasked with enforcing policies that affect personalized medicine innovation.  They presented their thoughts on the state of personalized medicine and their respective agencies’ roles, highlighting their progress. Both Janet Woodcock, M.D. and Elizabeth Mansfield, Ph.D. of FDA highlighted FDA’s efforts in bringing regulators and industry to the table to discuss the challenges of regulating personalized medicine products and services.  These discussions informed the agency’s new report—dubbed a blueprint for innovation—which includes major focus areas in building the infrastructure to drive and support personalized medicine and in creating a rapid drug development pathway for important targeted therapies.  They also acknowledged that changes are still needed at FDA to accommodate personalized medicine and that the agency will continue its leadership role by building a system to support the development of personalized medicines, including investments in regulatory science and by clarifying agency policies.

At the same time, Jeffrey Roche, M.D., M.P.H. from the Centers for Medicare and Medicaid services (CMS), underscored his agency’s time-consuming coverage decision-making process, which is based on published research used to determine what is “reasonable and necessary.”

Indeed more coordination is needed at the federal level.  Speakers representing academe, industry, and patients reinforced this sentiment, in addition to emphasizing the need for industry incentives to develop new products and services and a CMS reimbursement policy that can speed the adoption of personalized medicine by paying enough for personalized medicine diagnostic tests so that research and development costs are recouped.

Patient advocate and PMC-member Donna Cryer summed it up best, when sharing her thoughts on what can foster innovation and the adoption of personalized medicine: We need HHS level coordination, and a streamlined FDA process for personalized medicines and their diagnostic partners.  CMS needs to support the science of personalized medicine through a system of care that repays innovators for the research that goes into the development of these products.  And tax credits are necessary to help companies through what is still very difficult science. 

PMC is pleased by Rep. Eshoo’s leadership in advancing personalized medicine as evidenced by her participation in this event and her willingness to consider all of the policy proposals PMC and others have put forth.  We look forward to working with her to vet policy recommendations suggested by others and to see the Genomics and Personalized Medicine Act introduced in this Congress.

Looking Forward, Looking Back

September 13, 2011

At the Food and Drug Administration (FDA), I had a wonderful opportunity to spend nearly 20 years working in various capacities: in drug development science, regulatory oversight, and clinical pharmacology. Earlier this summer, I had the privilege to meet with the Personalized Medicine Coalition’s public policy committee to discuss the state of personalized medicine just after my departure from the FDA and before I began my new position leading the pharmacometrics and systems pharmacology initiative in the interdisciplinary Institute of Therapeutic Innovation at the University of Florida’s Research and Academic Center in Lake Nona (Orlando).  Personalized medicine will continue to be a passion for me in my new position.

The timing of my talk was serendipitous:  Dr. Steven Spielberg was just named as the new Deputy Commissioner for Medical Products and Tobacco at FDA. His perspective is strongly rooted in understanding disease at the molecular level, having served as director of the Center for Personalized Medicine and Therapeutic Innovation at Children’s Mercy Hospital in Kansas City, Missouri. And the FDA had just announced the draft guidance document for personalized medicine and companion diagnostics. This guidance should be seen as part of a mosaic of guidance documents from the FDA that will together guide the regulation of personalized medicine products. The Personalized Medicine Coalition has begun putting the mosaic together by listing the relevant guidance documents as a reference tool on its website.

I had a chance to reflect on the new direction FDA has taken over the past several years to embrace what we’re seeing in research and scientific discovery. Like the industrial revolution, the genomic revolution could take 60 years to fully unfold, but in the last ten years, the field and the FDA have made great progress. Many of these changes are leading researchers to re-evaluate how we focus research efforts, assess new therapeutics, and apply our shared learning through the R&D continuum.  As we’ve heard from the industry, researchers are stratifying medicines earlier in the R&D process and about 50% of new drugs have a biomarker that can potentially lead to a personalized approach. While many challenges remain, I am encouraged by the four-fold increase in Investigational New Drugs (INDs) and New Drug Applications (NDAs) that include genomic data since 2008.

To address this growth in genomic submissions, the FDA has new employees with expertise in genomics dedicated to review of these products and efforts to coordinate personalized medicine reviews will continue. I see a new era of personalized medicine not just in oncology but in cardiovascular disease, infectious disease, and neurodegenerative diseases, among others and the FDA is working to be ready.

I called on all members of the Personalized Medicine Coalition to find new ways to enable collaboration and to export the knowledge they are fostering at their companies and organizations to benefits for public health. By doing so, our combined efforts can lead to dramatic advances in improving therapeutics and healthcare. We are only just beginning to understand how new networks and powerful tools for sharing best practices can help us solve some of our most complex disease and drug response questions.

FDA Issues Draft Guidance for Rx/Dx Co-Development – What’s Next?

July 21, 2011

FDA released long-awaited draft guidance on its regulation of co-developed drug diagnostic combination products.  PMC asked FDA to issue a draft guidance on this topic since innovators had many questions about how regulation of these two products together would work.  I can describe it in one word: short.

It outlines a collaborative process through FDA where the device and drug centers will coordinate review.  It reiterates the FDA practice of using ‘generic’ descriptors of diagnostic tests in drug labels and offers some flexibility and examples around products where a drug might be ready to go to market but the diagnostic is not yet.

While the community welcomes FDA’s current thinking on the topic, given the brevity of the document, I wonder if it left much unsaid.

For example: The focus (which will probably be welcomed by sponsors) is on collaboration between the drug and device centers but no details are given.  Also, while the personalized medicine community generally agrees that FDA regulation of companion diagnostics should be risk-based, there is a lot of debate in the community about what FDA means by risk in the case of a diagnostic.

In recent months, PMC has been working with over 100 members to develop legislative specifications for the next iteration of the Genomics and Personalized Medicine Act.  I will provide more detail on this in an upcoming blog entry, but one of the key concepts of these specifications is to “incentivize personalized medicine by creating a transparent and predictable regulatory environment for personalized medicine products.”  While the FDA’s draft guidance issued last week certainly leaves me wanting more, I do believe this represents an important step in that direction.

Nevertheless, our efforts toward this goal must continue. The FDA is seeking comment on the document for the next 60 days, and I encourage you to submit feedback.  We also welcome your participation in a discussion here at The Age of Personalized Medicine Blog by submitting a comment below.  We expect that FDA will continue to expand its guidance in the coming months, and receiving input from all stakeholders in the development, regulation, and use of co-developed drug diagnostic combination products is essential to their success.

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