Archive for the ‘Clinical trials’ Category

Finding My Future, or, How to Coexist with Cancer

March 24, 2014

In October 2007, my identity was stolen.

In September 2007, I was a 39 year-old wife and mother of two young girls. Then, suddenly, I was a 39 year-old wife, mother of two young girls, and Stage IV lung cancer patient.

At the time of my diagnosis, I learned a majority of late-stage lung cancer patients die within one year. Just one year. One birthday. One summer. Would I make it to another Christmas? I didn’t know. Already a “glass half empty” kind of person, I wondered if this was my death sentence as the sense of a future ahead of me drifted away.

For the first six months, I tried traditional treatments, and I felt terrible. I was finding out what it felt like to experience the decline of death.

But here I am. More than six years later, alive and kicking. And personalized medicine is the reason.

My experience with molecular testing and targeted therapies
My first line of treatment was the classic carboplatin-taxol combo, combined with bevacizumab—the first of the newer, targeted therapies. Even though I was epidermal growth factor receptor (EGFR) negative and might not respond, I fit the common demographic for success closely enough that my doctor and I decided to try erlotinib with bevacizumab. That run lasted over two and a half years—precious time. I spent that time with versions of the most common side effects but otherwise felt pretty normal and lived life actively, something I never expected to do again.

During that time, I learned about the clinical trial for crizotinib on the news, and after three different people contacted me to pass along the story, I considered it an omen of sorts and asked to have my tumor specimen tested to see if I was a fit for this new personalized treatment.

When I found out I was ALK positive—and therefore likely to respond to the treatment—I felt relief. I knew how promising crizotinib already was and now I had my next plan in place. I have been on this targeted therapy for more than two years and I have been living a virtually symptom-free, normal existence with my daughters, with the hope for more.

Targeted therapies have been invaluable to my treatment. I know that I am very fortunate and remain in the minority to have my disease controlled so well. Frankly, that fuels my feeling of responsibility to do something productive to change things. So many—too many—die so quickly.

From my perspective, there are two important considerations for targeted therapies.

  1. We should use molecular testing as a way to inform treatment—not exclude access to drugs: I am enthusiastic about the value of molecular testing, and I also believe that its value lies not in its exclusionary potential, but in informing the priorities of a treatment plan.

    Having benefited over a period of almost three years from erlotinib when I tested negative for the genetic marker, I’d hate to see that same possibility be denied outright to others. I know that for some cancers and other illnesses, there is a concern about “overtreatment,” but in the lung cancer world, we’ll take whatever we get because our odds are so poor.

  2. We should better keep healthcare providers educated and up-to-date on the latest in molecular testing: I have heard horror stories about oncologists who don’t know much about the testing, never mention it to their patients, and trudge down the traditional paths without pause.

    We need better approaches to ensure doctors have access to the latest research and tools for diagnosis and treatment. I worry about the patient that doesn’t have the tools to advocate for their own healthcare.

Millions of people are depending on scientists, business people, and policymakers to keep working hard and collaborating to bring access to promising therapies to those in need and accelerate medical breakthroughs.

Now, I live with Stage IV lung cancer. It is a part of my body and part of my identity. My outlook on life has changed dramatically since my diagnosis, but my ability to take care of my daughters and live my life hasn’t at all. And that is incredible.

Molecular testing and personalized medicine gave me my life back, and my sense of a future back. While I’m realistic enough to know that my daughters are fairly certain to lose their mother before they are grown, I also know I have tools to fight with, and a responsibility to share my story.

We need earlier detection.
We need the tools to cure.
We need to increase survival for those, like me, who live with cancer.

A Look at the Regulation of Diagnostics

January 24, 2014

Participants at the upcoming Personalized Medicine World Conference 2014 (PMWC) will be engaging in thoughtful debate and discussion on some of the biggest topics in the field of personalized medicine. I anticipate a lively discussion with Andrew Fish, Executive Director of AdvaMedDx on the topic of regulatory issues in molecular diagnostics.

The regulation of diagnostic products is one of the most contentious issues within the personalized medicine community today. Regulatory issues have led to confusion and uncertainty in the industry due to the involvement of multiple agencies with varying standards. Consensus on solutions among kit manufactures and laboratory developed test companies has been hard to come by.

At the Personalized Medicine Coalition (PMC), we have heard from some who would prefer that the status quo is maintained; however, PMC contends that the status quo is not an option. While our members may not agree upon the exact course of action, it is time to acknowledge that action is needed to build a consensus around the development of an efficient, cost-effective process for bringing safe, high quality diagnostic tests to market in which patients, physicians, and payers can have confidence.

To initiate this process, PMC published Personalized Medicine Regulation: Pathways for Oversight of Diagnostics. The paper established baseline knowledge of the status of diagnostic regulation, and set the groundwork for future collaboration among industry, government, and other organizations.

To learn more about this important issue, with a look at the complex and diverse perspectives from key stakeholders, as well as to explore potential solutions, join me on January 28 at the PMWC 2014. Our discussion will look at areas of agreement and disagreement regarding the regulation of molecular diagnostics and likely scenarios for the future.

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 Look for additional posts from speakers and participants prior to the 6th Annual Personalized Medicine World Conference on January 27-28, 2014. For more information and the full agenda, visit: 2014sv.pmwcintl.com.

Randy Scott: Bringing Metcalfe’s Law to Genomic Medicine

December 11, 2012

Each year, the Personalized Medicine Coalition recognizes an individual whose contributions in science, business, and/or policy have helped advance the frontiers of personalized medicine. This year, the Leadership in Personalized Medicine Award was presented to Randy Scott, Ph.D., during the Harvard Personalized Medicine Conference on November 28, 2012 in Boston, Massachusetts. 

Receiving the 2012 Leadership in Personalized Medicine Award from the Personalized Medicine Coalition (PMC), Randy Scott reflected on his success as the founder and former CEO of Genomic Health, but also looked ahead to new opportunities with his latest venture, InVitae Corporation.

Scott received the award this week at the 8th Annual Personalized Medicine Conference at Harvard Medical School. “Randy has transformed our understanding of how medicine can be practiced by creating one of the most successful personalized medicine companies to date,” stated Brook Byers, a partner with Kleiner Perkins Caufield & Byers and a previous honoree. Past winners of the PMC Award include Janet Woodcock (FDA), Elizabeth Nabel (NIH), Ralph Synderman (Chancellor Emeritus, Duke University), and Leroy Hood (Institute for Systems Biology).

After a successful stint at Incyte, Scott founded Genomic Health in 2000 and led the firm for nine years, overseeing the development of the Oncotype Dx gene expression test for breast cancer. He modestly shared the credit with numerous colleagues. “My contribution was I probably did a good job of hiring a lot of people at Genomic Health who are way smarter than I was,” he said, naming in particular co-founder Joffre Baker, CMO Steven Shak, and CEO Kim Popovits.

As a graduate student in the early 1980s, Scott said he had been excited about biotech but worried he was too late. “All the exciting genes had been cloned! TPA, Factor VIII, human growth hormone, insulin,” he recalled thinking. Today, Scott said, “we’re on the precipice of incredible accelerating change in this field… Everything we’ve experienced to date pales in comparison to what we’re going to experience in the next 5-10 years.”

But he also shed some personal insight into the launch of his latest venture, InVitae Corporation. He said he is “unabashedly excited” about the future of personalized medicine. “Personalized medicine is really when disease happens to you—your friends or your family. Suddenly it’s no longer just an industry we’re working in but something so personal, so intense, and so emotional. We should never forget that.”

The Network Effect

Scott said reading Intel founder Andy Grove’s book Only the Paranoid Survive in the mid-90s, during his tenure at Incyte racing to identify human genes, was highly influential. In the book, Grove discussed the impact of Moore’s Law on the revolution in computing; Scott saw parallels with the biotech industry. “The way we were sequencing DNA [at the time] was so embarrassingly simple,” he said. Just as computing costs were plummeting, Scott reasoned it was inevitable that sequencing costs would also fall.

Perhaps more importantly was the concept of “the network effect.” Just as Metcalfe’s Law—the community value of a network is proportional to the square of the number of its users—drove change in the computing world, so too will it drive the future of biotechnology.

“Having a really cheap genome sequenced is really not very useful. We still see articles in The New York Times, ten years after the genome project, [saying] ‘so what?’ At some level, they’re horribly wrong, and at some level, they’re horribly right. We’ve not yet seen the network effect or the full implication of Moore’s Law.”

Scott said the community is still “1-2 years away from the inflection point” where the cost of sequencing reaches the point that will trigger “massive consumer demand.” The value of genome sequencing will be most strongly felt in the network effect. “How we connect that genomic information across millions and millions of individuals… Somebody can be sitting at a computer, link into the network, and find how a mutation and how it correlates with their patient and a patient somewhere else in the world.”

Scott said he was also a believer in what he called the “Law of Finite Genomes.” The human genome is like a complex finite puzzle with about 150,000 pieces (20,000 genes and 100,000 non-coding RNAs). “All common diseases are really rare diseases,” Scott said, with cancer a prime example. “Medicine goes from an infinite game to a finite game,” he said. By comparing lots of genomic information, we can begin to rule things out.

Patients, Patients, Patients 

Scott was inspired to launch Genomic Health when a close friend was diagnosed with colon cancer in 1999. For the first time, Scott was personally struck by the chasm between science/technology and medicine. “We’ve got to bridge the gap—bring the science into clinical practice,” he said.

The focus at Genomic Health, Scott said, was “patients, patients, patients.”

“I’m not sure we had a model other than this maniacal focus on patients that wouldn’t be denied,” he said. If we could really do the science right, the science would sell.” Genomic Health spent an enormous effort on clinical studies.

“Clinical data wins over physicians, and it is physicians that win over the payors,” Scott said. “The onus is on us as an industry to build the value proposition [for payors]… so physicians have to adopt those products. If physicians adopt, they will drive payers to cover.”

Scott left Genomic Health this year to launch InVitae, spurred by the impact of rare genetic diseases affecting members of his family.

In 2000, Scott’s nephew had a daughter with galactosemia. Fortunately, the disorder was diagnosed within 48 hours of birth, and her diet could be changed, otherwise there could have been “a dramatically different outcome.” In 2005, an adopted nephew collapsed on a tennis court and died from hypertrophic cardiomyopathy. Advanced screening could have saved his life, but nobody knew any family history of cardiac disease, he said.

Finally, one of his wife’s relatives had a young son who developed serious seizures at age 2 years. The infant is developmentally impaired and severely autistic. Earlier this year, Scott revealed that exome sequencing of the child and his parents revealed a single de novo point mutation as the putative cause of the disorder. This is unlikely to provide any tangible medical benefit, but “it gives a clue into potential causes of these disorders,” he said.

Ridiculous Goal 

Scott said his goal in launching InVitae was to bring the power of genetics into the real world of clinical practice. “We have a ridiculous goal,” he said. “We want to aggregate all of the world’s genetic tests into a single assay—for less than the cost of a single assay today!”

In other words, InVitae plans to collapse all Mendelian inherited traits into a single assay that can be performed “reproducibly, at high quality and at reasonable cost for the medical system. So instead of going into these diagnostic odysseys… every parent thinking about conceiving a child can know exactly what their carrier status is and what disease risks lie in their family.”

The initial assay will essentially be an elaborate gene panel, but Scott’s plan is eventually that this will lead into whole-genome sequencing (WGS). Scott believes that “within 10-20 years, everyone in any developed health care system will be able to be provided with a low-cost [WGS] analysis at birth… We’ll be talking about managing your genome over the course of your lifetime.”

As for the question of how to deal with the plethora of data, “that’s Metcalfe’s Law, the network effect,” said Scott. “Much of the data won’t be of value to the patient or physician ordering the test. But collectively, they will be massively valuable to the research community.”

We’re big fans of “Free the Data!” said Scott. The universe of clinical genetic data “won’t be a database held by one company or one academic institution, but you’ll see a massive movement over the course of the next decade to make data broadly available within the research community.” This will create a huge disruption in medicine, Scott predicted, a shift from phenotypically driven medicine to more of a genotype foundation as sequencing costs fall and the network builds.

“Everything will drive off the genotype and it will move very fast,” he said. “This is a given. To me, this is the investment thesis. This will be the place to be, the chance to help people suffering from rare diseases. At the end of the day, every disease is rare.”

InVitae is building a strong management team. The company recently merged with Locus Development, a start-up co-founded by Sean George and Michele Cargill, founding scientists at Navigenics. Steve Lincoln and Jill Hagenkord, both formerly with Complete Genomics, also joined the cause this year, as did Reece Hart, former manager of research computing and informatics at Genentech.

- This article was first published at the Bio·IT World website on November 30, 2012.

Levin, O’Kelly Provide Perspective on Decades of Personalized Medicine Progress, Urge Action and Support

May 22, 2012

On Tuesday, May 8, 2012, the Personalized Medicine Coalition (PMC) welcomed our chairman, Stafford O’Kelly, President of Abbott Molecular and keynote speaker, Mark Levin, Partner and Co-Founder of Third Rock Ventures to its Eighth Annual State of Personalized Medicine Luncheon. The event brought together PMC’s members, partners and other stakeholders involved in realizing the future of personalized medicine for researchers, industry leaders, patients, caregivers, advocates and policymakers.

Stafford O’Kelly reminded us, in his introductory remarks, of the progress and success we’ve made toward achieving personalized medicine in practice within the past year alone. Just last week we saw that Xalkori is showing progress in fighting certain childhood cancers. O’Kelly pointed out the assurances by the FDA that co-approval of drugs and diagnostics will occur more frequently. He also challenged attendees to think about what they can do “to accelerate the shift toward personalized medicine in a way that will improve treatment outcomes for the patient while, at the same time, lower overall costs for our health care system.”

Mr. Levin sought to use his significant experience and background in venture capital, product development and marketing to answer O’Kelly’s provoking question during his keynote address. He urged attendees to support personalized medicine. He explained that “personalized medicine is one of the most important things in medicine today” and lauded its potential to reduce safety challenges, increase efficacy, and improve productivity in the pharmaceutical industry.

I agree that we are at a point where the scientific and clinical progress made in personalized medicine is undeniable. But to echo Stafford O’Kelly’s call to action:  “We need to get the right stakeholders involved to help develop pathways for accelerating growth in the field….We need commitment from payers, providers and patients.”  In order to continue to make progress against disease and improve outcomes for patients, it is necessary as O’Kelly and Levin said, for the entire ecosystem of players to focus efforts in the direction that scientific discovery points us – toward targeted, patient-centric approaches to research and care.

We hope to continue the discussion around these themes and the future of innovation, specifically in cancer research and care at “Turning the Tide Against Cancer Through Medical Innovation,” a national conference that the Personalized Medicine Coalition, American Association for Cancer Research and Feinstein Kean Healthcare are co-hosting on June 12, 2012.  I encourage you to join us in Washington, D.C. as we look to identify and build support for an environment that sustains innovation and drives our evolution toward personalized cancer care.

Personalized Medicine Opens New Pathway to Get Needed Treatments to Patients

April 26, 2011

Should the Food and Drug Administration (FDA) provide post-Phase 1 study accelerated review of biomarker-linked cancer medicines? In a recent, provocative article in the New England Journal of Medicine, Bruce Chabner, M.D., argues that they should. Dr. Chabner, former director of the National Cancer Institute’s Division of Cancer Treatment argues that our growing ability to target therapies to patient subgroups based on molecular or genetic diagnostics necessitates a shift to earlier approval.

In his editorial, Early Accelerated Approval for Highly Targeted Cancer Drugs, Dr. Chabner, now at Massachusetts General Hospital Cancer Center, highlights research on two targeted therapies to illustrate how biomarkers can be used to match therapies to patients most likely to benefit and/or least likely to suffer harm from an experimental treatment:  PLX4032 (for patients with BRAF mutated melanoma) and crizotinib (for patients with EML4-ALK fusion in non-small cell lung cancer).

Both of these treatments were able to progress directly from Phase 1 to Phase 3 studies through use of validated biomarkers, Dr. Chabner says. But with the typical cancer drug taking seven years to complete clinical trials and gain FDA approval, the process is still “expensive and time-consuming, usually taking two to three years to reach survival end points.”  In addition, phase 3 trials still require a control group to receive the standard of care, depriving some patients of the experimental treatment with potentially better response rates and less toxicity.

While other accelerated paths provide patients access to promising therapies (i.e., compassionate-use protocols and accelerated review), if we are able to define populations of patients with high response rates in phase 1 trials, prolonging drug testing and approval raises important issues. A patient with an incurable disease and the right biomarker will want access to a new therapy. Dr. Chabner argues that the new age of molecularly-guided medicine is cause for an even more rapid path to approval: “Given trialists’ ability to define patient subgroups with responsive tumors in phase 1 trials, I propose that for diseases lacking therapies that meaningfully extend survival, the FDA should set flexible standards permitting accelerated approval of new drugs after phase 1.”

Dr. Chabner’s proposal illustrates the growing and likely dramatic impact that personalized medicine will have on research and development as well as regulatory and payment standards. It also offers a potential new pathway for addressing the serious challenge of how to get potentially life-saving medications to patients as expeditiously as possible while maintaining FDA’s gold standard for safety and efficacy. His suggestion reinforces the critical need for science and policy to work hand in hand in the advancement of personalized medicine. As the science leads the way in increasing our understanding of what therapies work best for which patients, regulatory policy will need to evolve as well.

Genomes to Health: The Path to Better and More Personal Cancer Care

May 20, 2010

We now recognize that most cancers are not one disease, rather they appear to be many complex diseases with distinct causes. Even so, doctors make decisions every day (about 700,000 decisions every year in the U.S. alone) about how to treat individual patients’ cancers without the benefit of tools that could define important underlying characteristics of each and every unique tumor. Much-needed guidance is lacking for choosing among treatment options for the individual.

Genomic information and tools that have emerged in the past decade could change this—starting today. At Duke, we have been wrestling with how to translate genomic science and information into something that can be made practical and accessible to patients and their physicians.

The key to making these novel findings from genomic medicine a part of standard medical practice is to show that they actually improve patient care and disease outcomes. Genome-guided clinical trials and research from a new cancer registry led by the Duke Institute for Genome Sciences & Policy are moving genomics into clinical care for breast, prostate and lung cancer. We plan to expand our efforts in other cancers, as well as other common diseases such as type 2 diabetes. 

Through participation in these trials or the registry, some patients and their physicians at Duke and in an emerging genomic trials network are now getting early access to this kind of genomic information while they help build the future of medicine, which we believe can be both better and more cost effective.

We call this initiative “Genomes to Health”, and here’s how it works. A person with breast, lung or prostate cancer comes to Duke or one of our network partners around the country for evaluation and consents to having a biopsy for genomic and genetic analysis. Based on the characteristics of the patient’s disease, and the results of their biopsy analyses, several options are possible including:

  • The patient is deemed eligible for one of the ongoing genome-guided clinical studies in breast, lung and prostate cancer and is offered the opportunity to enroll in the trial.
  • The patient is not eligible for one of the Duke trials but may be eligible for an ongoing trial outside of Duke and is referred to that study.
  • If the patient is not eligible for an ongoing clinical trial, either at Duke or at an outside institution, the patient can be entered into a registry study in which their clinical outcomes will be followed for future study and possibly future eligibility in a genome-guided study.

For more about ongoing genome-guided clinical trials and the registry, visit genomestohealth.org.

This initiative at Duke is just one of many such efforts around the country to use robust health databases and informatics tools to combine clinical and genetic information to support higher quality, more personalized care.  Innovations like these are part of the answer to containing costs while improving outcomes and the patient experience.

Geoff Ginsburg is director of the Center for Genomic Medicine at the Duke Institute for Genome Sciences & Policy.


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