John J. Castellani Remarks Before The Personalized Medicine Coalition

I am honored to be here today. I appreciate the invitation from Ed and the PMC and I am excited to talk about the power and potential of personalized medicine.

 

While I’m excited, I’m also humbled. Making the potential of personalized medicine a reality is urgent, and it is hard. I’m humbled by the dying wish of Adriana Jenkins, a breast cancer patient whose life was prolonged by a personalized medicine, Herceptin, but who ultimately lost her battle against the disease earlier this year. Most of you here today probably have read the commentary she published in Forbes called “A Dying Wish,” in which she called on biopharmaceutical research companies to do more to bring forward the next generation of targeted therapies. 

 

As Ms. Jenkins noted, this is no small task. The science is very complex – it seems the more we learn about the influence of genetics on disease and treatment response, the more we realize we don’t know. And the technology is disruptive, posing challenges to business models, regulation, and policy.  So, the real challenge we face today and into the future is: can we overcome the barriers to personalized medicine and fulfill its potential?

 

I’m here today to tell you that I believe we can. Looking back 10 years from now, I believe we will be able to say we met the challenge, and we fulfilled Adriana’s dying wish.  
I want to make four key points today about why we can, and why we must, advance the field of personalized medicine.

 

First, biopharmaceutical research companies are strongly committed to advancing personalized medicine. We are heavily invested in this field, and are striving for new advances and their adoption in the clinical setting. 

 

Second, personalized medicine offers enormous potential to address unmet medical needs of patients with cancer, HIV/AIDS, and many other serious diseases. It also holds potential to help us meet the challenge of rising healthcare costs by avoiding treatment complications and making sure each patient gets the most effective care possible. 

 

Third, as we face continued economic difficulties, it is more important that ever to foster growth in innovative sectors like those advancing personalized medicine. As this field flourishes, it will be a source of high quality jobs. 

 

Finally, as I noted earlier, we face significant challenges in accelerating growth in this field – scientific, business, regulatory and policy challenges. Together we must break down the barriers and move this field forward. 

 

As I was thinking about what I wanted to say here today, I was reminded that this week is the 30th anniversary of the first time HIV/AIDS was ever mentioned in a medical journal. The story of the great strides we have made against this disease is a great model of what can be accomplished when patients, clinicians, regulators and researchers in the public and private sectors work together toward a common goal.

 

When that medical journal article was written, things were pretty grim. Practically nothing was known about HIV/AIDS. Patients were dying of diseases that previously had been extremely rare. There were no treatments available. And physicians could only try to make patients as comfortable as possible in their final months.

 

Today, while we still have not beaten HIV/AIDS, it is no longer a death sentence for patients with access to medicines. Despite the complexities of the disease and the constantly mutating virus behind it, researchers came together to define the illness, understand the virus, develop drugs and combine them into effective cocktails. Thus transforming HIV into a chronic condition – a disease patients live with and not die from.

 

In addition to exacting an enormous human toll, AIDS was very expensive.  An AIDS patient in the early 1990s would likely face successive hospitalizations for a variety of opportunistic infections as their immune system collapsed and they succumbed to the disease.  Tuberculosis, hepatitis, Kaposi’s sarcoma, and many other diseases could have landed the patient in the hospital, and each extended stay cost tens of thousands of dollars.  These costs led to dire predictions about the disease’s impact on health care spending.

 

Fortunately, the same advances that saved so many lives also averted the catastrophic costs associated with caring for acutely ill patients.

 

With similar drive and collaboration we can tackle the scientific, regulatory, policy, and delivery challenges that hinder the adoption of personalized medicine.

 

As you know, 2010 was the 10th anniversary of the sequencing of the human genome. 

 

I am sure many of you remember that when that was announced, there was great speculation that this would quickly lead to a new age of innovative cures and treatments for a whole host of diseases. 

 

Now, 10 years later, many are asking where are the miracle cures? Some have criticized the scientific community for over-promising and under-delivering.

 

But those critics miss two important points: First, there has been incredible progress and, second, translating the basic information from the genome into treatments has been much more difficult than expected. 

 

Sequencing of the human genome, while important, was just the beginning. 

 

Just last week, we saw a new article in the Journal of the American Medical Association reporting that many gene/disease associations identified in small early studies don’t pan out in larger trials. And just this week, we are hearing of exciting progress in targeted cancer treatments reported at the American Society of Clinical Oncology conference.

 

We must remember that science takes time, and that each success is preceded by many failures, that each success builds on the last to achieve dramatic progress over time. And, that the scientific, technical and policy challenges we face today are some of the greatest ever yet explored. 

We also must point to the important steps forward that we already have made. In 2007, the first personalized medicine for HIV was approved, and the HIV/AIDS and personalized medicine stories converged. Using a diagnostic test, health care providers can identify which patients will benefit from this drug, thus choosing the best treatment options for patients who may be resistant to or intolerant of other available therapies.

 

This is just one of several important milestones of our progress in personalized medicine, and I’m confident there will be many more to come in the years ahead. As these advances demonstrate, the biopharmaceutical sector is fully committed to advancing personalized medicine. 

 

Several years ago some believed that the biopharmaceutical industry was opposed to personalized medicine. I hope that everyone in this community now knows that we are fully engaged and committed. This approach has become central to how we make decisions and approach drug discovery.

 

Our companies are driven by innovation – by applying science to meet the needs of patients. The science is leading us in this direction and we are adapting the way we do research as a result.

 

Recently a survey by the Tufts Center for the Study of Drug Development put the shift in the biopharmaceutical sector into concrete terms for the first time. Of the companies surveyed, 94% said that they were investing in personalized medicine research and 100% said they are using biomarkers in the discovery stage to learn more about compounds. This research has required large investments in new tools and training.

 

Looking at the entire pipeline, companies report that12-50% of compounds being researched are personalized medicines. This large proportion reflects large increases in investments: Over the last 5 years, companies report that they have seen a roughly 75% increase in their investment in personalized medicines. 

 

The Tufts survey reflects what we are seeing and hearing from our members. For example, the new lung cancer drug, crizotinib, is currently in review with FDA and, like other personalized medicines before it, this medicine promises to offer certain patients a new, effective approach to fighting their disease. Study results reported at ASCO a few days ago show that this work is bearing fruit. One study showed that patients receiving crizotinib – which is targeted to patients with non-small cell lung cancer who have a specific genetic variation – had dramatically improved survival rates after one year. Another study showed that a new targeted therapy for melanoma has a dramatic effect on survival for patients with a specific genetic mutation. 

 

While there are just a handful of medicines that today can be strictly described as “personalized medicines,” the commitment of our sector, along with the rest of the research ecosystem is certainly bearing fruit. We should not forget that just 10 years out from the sequencing of the human genome, we have made real progress. 

 

But, as in any scientific enterprise, translating a broader understanding of the human genome and using that knowledge to target disease and create new and better treatments is an extremely challenging process.

Advancing personalized medicine had required significant investments in new technologies. Companies are still learning how to efficiently validate biomarkers and conduct clinical trials for personalized medicines. Co-development of diagnostics also opens up a whole new set of challenges.

 

According to the Tufts survey, “While it is unclear if pharmacogenomic data have helped streamline the R&D process —or have only complicated it—early indications show that development of personalized medicines is commanding more resources and fomenting more corresponding organizational change than is generally appreciated outside the industry.”

 

Ten years from the sequencing of the human genome personalized medicine has not yet transformed patient care in the vast majority of diseases. While we are humbled at the complexity of the science and the challenges of translating it into better tests and treatments, this should not be reason for us to reduce our effort, but rather to redouble it. Patients like Adrianna demand that we do.

 

We can see how important this is to patients through the examples of progress that already have been made. The examples are familiar to all of us but think again about what we have achieved in the last decade: medicines like Herceptin and Gleevec and new ways to tailor treatment of older medications like Coumadin.

 

Gleevec, for example, has completely transformed the outlook for many patients with chronic myelogenous leukemia. After six years of treatment 88% of patients on the medicine survived. It is important to note that these benefits were not fully known when Gleevec was first introduced. FDA approval was based on evidence showing the drug had an effect at the cellular level. It wasn’t until six years later that studies were completed confirming the treatment’s stunning survival benefit. 

 

Similarly, Herceptin was approved for breast cancer patients with HER2 positive tumors in 1998 and further research in 2005 showed that it reduced recurrence by 52% in combination with chemotherapy. 

 

The field of personalized medicine is yielding benefits in other areas as well. For example, researchers have identified a genetic variation that influences how quickly a patient will metabolize warfarin, a commonly used blood thinner. This information can help doctors tailor the appropriate dose to each patient.

 

And personalized medicine will help us shift the emphasis in health care from reactive treatment to prevention of disease. Genomic science will provide us tools to identify peoples’ risk for disease before symptoms even develop, helping them avoid serious health consequences and costly hospitalizations. As noted by Dr. Ralph Snyderman at Duke, a recipient of PMC’s leadership award and champion of prospective, personalized medicine, “health care costs are less when appropriate interventions are taken before a catastrophic event occurs.”

 

It is important to recognize how these advances are not just a solution for patients, but also to the challenge of rising costs.  This is because they help patients avoid costly complications and hospitalizations due to adverse reactions and by helping to make sure each patient receives the best, most effective treatment available. 

 

We can see this happening already in the personalized medicines now available to patients. For example, a 2006 report estimated that the use of a genetic test to properly dose the warfarin could prevent 17,000 strokes and 85,000 “serious bleeding events” each year and avoid as much as 43,000 visits to the emergency room. 

 

If the 2 million people that start taking warfarin each year were to be tested at a cost of $125 to $500 per patient, the overall cost savings to the healthcare system would be $1.1 billion annually. 

 

In addition, a study has found that a cancer test could save up to $2,000 in direct patient costs by helping some women with breast cancer determine whether they would benefit from chemotherapy after surgery. 

 

Personalized medicine is good for patients, it’s good for health care, and it’s also good for the economy. This is the kind of leading edge innovation we need to be supporting right now to spur creation of jobs here in the U.S. 

 

Innovative research sectors like ours create high-quality, high-paying jobs that have ripple effects. For example, our latest data shows that the biopharmaceutical sector directly supports more than 650,000 jobs and indirectly fuels more than 2.4 million addition jobs in other sectors such as suppliers and service providers, a multiplier effect of 3.7.

 

These jobs and the tax base these companies provide drive local, state, and national economies. Other countries are also recognizing the economic benefits of the life sciences sector and are seeking to attract the research enterprise. For example, Singapore has set a goal to become the “biopolis” of Asia, the Indian government is building 20 biotechnology parks throughout the country and the European Union has a large public private partnership to boost health care innovation.

 

Given the benefits to both patients and the economy, we need to make sure the U.S. stays competitive as other countries invest in infrastructure and offer incentives to draw in companies. 

 

But while the potential for personalized medicines is significant, so are the barriers to moving it forward. 

 

As I have mentioned, the scientific challenges remain daunting. In many instances, the relationship between disease and genetics is proving much more complex than initially imagined. Effective partnerships are essential to overcoming these challenges, especially because the field of personalized medicine is so broad.

 

The Biomarkers Consortium is just one example of an effort to combine resources to scale up and speed up research to enable personalized medicine. This public/private partnership among the Foundation for NIH, PhRMA, FDA, and others is working to discover and validate biomarkers and has already made important findings, such as the discovery of a predictive biomarker for Type 2 diabetes. 

 

In addition to scientific challenges, we also face regulatory and policy barriers. 

 

Federal regulation of diagnostic and laboratory testing remains unclear, creating uncertainty for innovators and providers. And efficient pathways for premarket review of drug/diagnostic combinations need to be more clearly defined by FDA – we appreciate the work FDA already has done, and look forward to the planned release of draft guidance on this topic. 

 

In addition, as the field of comparative effectiveness research moves forward, it is important for it to align with and support the emergence of personalized medicine. Done well, CER can close evidence gaps involving personalized medicine, and can help illuminate the role of genetics and other factors that cause patients to respond differently to treatments. Done badly, CER will rely on broad population averages that do not incorporate genetic information and obscure patient differences. 

 

To quote one of the pioneers of personalized medicine, Francis Collins, "We need to be mindful of the goal of comparative effectiveness research and not lose all that we have gained in understanding how individuals differ and how that could be factored into better diagnostics and preventive strategies."

 

Further, as policy makers define new performance measures and provider incentives to improve health care quality and efficiency, it is important for them to facilitate adoption of novel, promising advances emerging from personalized medicine. Incentives that seek to hold down costs based on patient averages conflict with patient-centered care and the science of personalized medicine.  

 

Personalized medicine is an example of how innovation provides a path forward to the goal we all seek – high-quality, high-value, patient-centered care. Health care delivery and payment policy need to be better-aligned with this path. For example, personalized medicine means the development of high-value treatments targeted to a small patient group using advanced diagnostics. If reimbursement policy only looks narrowly at per-unit costs in a budget silo, it will fail to reflect and incentivize the full value of personalized medicines.  

 

Finally, health information technology can, and must, play an important role in advancing personalized medicine. Effective health information systems can make sure physicians and patients have the information they need at the point of treatment decision-making, including genetic information. They can make sure this information is seamlessly transferred from one provider to another. And they offer new tools to generate evidence on new tests and treatments.  

 

Going forward, there will, of course, be other challenges that test us. Those of us who strive to see the future, who understand see the power and potential of individualized medicine as well as the power and potential for innovation to transform healthcare, understand that we are at a crossroads.

 

Let me offer you one more story as an example of this crossroads. It’s the story from a biopharmaceutical research company seeking to make good on Adriana’s dying wish and bring personalized treatments to patients. 

 

One of our member companies was working to develop a new therapy for an area of high unmet need in oncology.  This drug failed in Phase III clinical trials when only 8 percent of patients experienced a strong response, while the majority of patients taking the experimental treatment did not demonstrate a clear benefit.  

 

Despite this failure, the company pressed forward. Discovering just what triggered the response in the 8 percent proved extremely challenging and time-consuming. Researchers conducted extensive additional studies and brought in partners from outside the industry, including a specialized biomarker discovery company and the National Cancer Institute.  The effort to bring this therapy forward for patients continues today, even as patent exclusivity has all but run out.

 

This perseverance and commitment by the company, its researchers, and its partners is what’s needed to fully realize the vast potential of personalized medicine.

 

Today we are confronting choices and challenges to innovation which could undermine this country’s global leadership role. Working together, we can help create appropriate policies and incentives to help new and better science emerge.

 

Alternatively, we can become complacent and resign ourselves to a healthcare system where out-of-date regulatory and measurement standards result in a stagnant level of health care. I think we all agree that patients deserve more.

 

The challenge is whether we embrace a 21st Century healthcare system that marshals the latest, best science, scientists and technology to provide the best possible treatment options for individual patients.   

 

Or, will we choose – and it is a choice – to change our frame of reference and regard our current medical achievements as good enough? 

 

The answer, I hope, is clear.

 

The patients we all serve and who wait and hope for better treatments and even cures deserve our best efforts. Patients like Adriana Jenkins. That means driving the science forward and creating an environment that embraces change and opens the door to personalized medicine.

 

In short, our task is not just to see the future but to enable it.