January 1, 2017 (Vol. 37, No. 1)
Where Do You See Opportunities?
2017 not only ushers in a new year, but a new U.S. presidential administration as well. GEN interviewed top biotech/pharma CEOs to find out what they thought might be in store for the industry and what they would like to see happen in the new year. I think you will find their responses timely, thoughtful, and instructive.
This is part 3 of the GEN CEO Perspectives Roundup. It consists of five parts.
Part 1: What Would You Tell President-Elect Trump?
Part 2: Key Challenges
Part 4: Regulatory Initiatives
Part 5: Disruptive Technologies
GEN: Where Do You See Opportunities for Growth in the Industry?
Mr. Manzello: The simple answer is to follow the trends in industry investment, which is a key indicator of the opportunity and potential of the next generation of therapies. The onset of antibody drug conjugates and bi-specific antibodies come to mind, as well as the growth and the acceptance of immunotherapies, and cell and nucleic-acid therapeutics, such as gene therapy, DNA, RNA, vaccines, and even direct RNA-based therapies.
Dr. Cohen: Neurology is becoming one of the most rapidly advancing new areas for therapeutic development, based on new understanding of the nervous system and the availability of new technologies, and cancer and immune system therapies have entered a new age. That said, it's a challenge to pinpoint where innovation will succeed next. By its nature, innovation is unpredictable. What we can say with confidence is that the level of scientific understanding, and the number of tools that can be brought to bear against human disease, are now at the greatest level in history. Technologies such as rapid, cheap genome sequencing, CRISPR-Cas 9, RNA interference, immuno-oncology, gene therapy, bispecific antibodies, and others are opening entire disease classes to intervention. This is by far the most exciting time ever to be working in our industry.
Mr. Leschly: We're seeing the convergence of information coming out of the Human Genome Project with much smarter drug development activities, like being able to subset populations and turn big diseases like cancer, asthma, and heart disease into smaller, manageable categories. We should have the opportunity in a few years to dissect those major diseases and put patients into specific subsets that can then be treated with more targeted therapies where you can expect to have a much better outcome.
It was more of a shotgun approach in the past: where if you had a 10, 20, or 30% hit rate, you were happy. Those types of studies and clinical trials, as well as the overall approach, are neither sustainable nor fundable. A better understanding of genetic and epigenetic mechanisms underlies much research today. And this comes back to the importance of fundamental research.
Mr. Connor: Everywhere, but I see nine areas to focus on. 1) Better nutrition and exercise practices for America from grade-school on up, at all socio-economic levels. 2) Molecular biology and, in particular, advancing our understanding of genetics/epigenetics/stem cells and their application to realize the potential of personalized or population-specific medicine, disease causation, and pre-symptomatic disease detection. 3) Keeping the pressure on understanding the genetic and environmental causes of cancer and how to identify it early, and how to cure it. 4) Incenting and accelerating less invasive medical devices (wearables/surface/patches) as well as home monitoring solutions that result in immediate notifications of and reactions to health problems. 5) Leveraging life-science, information, and communications technologies as well as food and healthcare distribution and access to improve wellness as a cultural transformation throughout America at all socio-economic levels. 6) Investing in defenses (e.g., vaccines and therapies) and solutions to the biggest threats to Americans’ life and longevity. 7) Streamlining the regulatory process. 8) Streamlining, simplifying and reducing the cost of the healthcare delivery process. 9) Better education and access to technologies and solutions at all socio-economic levels.
Mr. Equels: The shape of things to come is in immunology, especially in cancers and infectious diseases. Our two products, Ampligen and Alferon, are staged to be major players in this high-growth area, drugs that utilize the body’s natural, innate and adaptive immunity to affect a cure.
Mr. MacMillan: Improving our capacity to accurately detect and identify disease, and to do so earlier, are key growth opportunities. There has been sustained investment in the diagnostics space, particularly in the past several decades, but vast potential remains. We know that early detection saves lives, by allowing patients to be treated before their disease becomes life threatening. Early and accurate detection also saves our healthcare system dollars. It is much more economical to find and remove precancerous lesions, for example, than to treat a woman for cervical cancer.
Dr. Brandon: Let me bang my own drum for a moment and say that one of the biggest challenges/opportunities is managing sepsis better, diagnosing it objectively (with a diagnostic test), preventing it, treating it earlier, and better targeting that treatment by narrowing antimicrobial choices. This is going to require quite a change to what currently exists in sepsis diagnosis and also in treatments and therapies. It is hard for clinicians not to plaster critically ill patients with antibiotics when they are suspected of having sepsis, when there is no gold standard diagnostic for it.
I would like to see more personalized sepsis management (more relevant information), and that is only going to occur if we do two things. One is that we begin to introduce host response-based diagnostic and monitoring tests—which we know can be earlier, faster, and more reliable. And two is that we need quicker and faster technologies that will advise on antibiotic resistance of the offending pathogen.
Today, host response can detect the type of infection, but not the specific antibiotic resistance of those pathogens causing the septic response. You need both sets of information quickly and reliably to treat those patients quicker and more effectively, and save more lives and costs.
There is also a huge opportunity at the intersection of information technology and healthcare. We're starting to see the birth of this as an industry, often referred to as Big Data. Integrated health systems (Affordable Care Organizations, e.g., Intermountain Healthcare) have been using data and informatics for a lot longer than the majority of health systems. And they’ve used that data to their advantage—to improve mortality rates, improve standard of care, and drive down costs. I see genomic and genetic data as being a huge part of personalized medicine as we move forward.
Another opportunity is companion diagnostics to narrow or target therapies. We're seeing a lot of this in oncology, but less so in sepsis and infectious disease. The best example, of course, being breast cancer and the BRCA gene and allowing that test to better drive and target treatment.
Another area of opportunity is immunotherapy; it’s beginning in cancer treatment, but I also see immunotherapy as having a major role in the better management of sepsis patients, patients suspected of sepsis, and patients who are at risk of developing sepsis—such as the immuno-compromised patient.
Dr. Lichtenberg: Immuno-oncology and personalized medicine are two key drivers for new, efficient and effective therapies for a broad range of indications. Again, U.S. companies and academic institutions are among those who spearhead these new paradigms, globally.
Dr. Liu: I see growth in five sectors:
Genomic diagnostics that are coupled with big data informatics: These technologies are very powerful and can begin the customization of preventive and therapeutic care. But how this will be implemented will need new thinking concerning reimbursement and whether access to these tests should be in the control of physicians.
Gene therapy: Practical applications of gene therapy approaches, especially with CRISPR-Cas9 technologies, will see a significant expansion. This will spawn a support industry in terms of vector delivery systems. Additionally, many diseases will be amenable to gene therapy approaches.
Wearables and personalized devices: These will be clear adjuncts to standard medical care. Individualized monitoring of a host of parameters, integrated for personal and medical applications, will engage patients in their own care as well.
Probiotics and Microbiota: As knowledge increases about the role of the microbiome in health and disease, monitoring and manipulating the microbiome through probiotic intervention will be a new area for investment.
Medical informatics: Secure, accessible, and flexible information systems with portals for patients, the healthcare system, and healthcare providers will progressively be important, not only for improved health but also for reducing costs in an inefficient system. Medical informatics will also need information concierge services to navigate information flow and billing conflicts. The genome sequence of individual patients will become an important part of patients’ medical information.
Dr. Wilson: One of the greatest opportunities for growth continues to be in the treatment of cancer. In the past five years, more than 70 new oncology drugs have been approved, including the groundbreaking class of immunotherapy drugs that are extending the lives of patients with some of the deadliest forms of cancer.
These new cancer medicines are also making it to market more quickly. In 2015, the median time from patent filing to FDA approval was 9.5 years in the U.S., down from 10.25 years in 2013. And a few drugs have sped through the process in just four years, thanks in part to the FDA’s Breakthrough Therapy designation, which expedites approval for groundbreaking treatments.
These innovations in science, clinical development, and the regulatory framework have ushered a “golden age of oncology,” and these innovations have many experts talking about turning many cancers from a death sentence to a chronic disease, as we have done with other diseases such as hepatitis and HIV.
Other opportunities for growth in Biotech and Pharma are in the discovery of new medicines for inflammation and neuroscience. Inflammation stands to benefit from the significant investment in oncology drug discovery and development, as many of the molecular targets and pathways play dual roles in both disease areas. And, although neuroscience has been characterized by one of the highest failure rates for new medicines, we continue to see a significant investment in basic biology as well as the technologies (animal models, imaging, surrogate biomarkers, etc.) that have fueled product approvals in the areas of oncology and rare disease over the past two decades. I am optimistic that progress will accelerate over the next two decades, just in time for our aging population.
Dr. Schwieterman: With the hurdles that we face, also come opportunities. I like to view most challenges and problems this way, as flip-sides of each other. You have a hurdle to overcome, but on the other side of that is the opportunity.
In the early days of clinical development, with biotechnology in particular, there were tremendous gains made across a wide variety of disease areas. I think that progress has now stalled to some degree. For example, the ability to precisely target specific patient populations has presented itself as a challenge. But there is also an opportunity there. If we really change our focus to a different sort of paradigm where we're actually using biomarkers to identify sub-populations, that is a clear example of a challenge that is also an opportunity.
Ms. Cournoyer: The potential for growth is in the diagnostic space, which today is constrained by low reimbursement levels. I’ve seen innovative companies decide not to launch numerous new, exciting assays because they can't afford the business model, given the low reimbursement levels. The reimbursement level stifles innovation. We're at a turning point where patients could be receiving these tests, which could lead to significantly better treatment for cancer patients.
Once we get to routine testing associated with DNA, RNA, or protein, that will be an opportunity for growth in this country and for improved healthcare.
Dr. Clarke: The opportunity, again, is based on what the President-Elect Trump has already stated publicly regarding his plans to revise, not necessarily remove, the Affordable Care Act, but to have something different in its place to serve all Americans. That certainly could provide a potential economic benefit to both the individuals and the payers as well as the companies that are developing the drugs.
Also, the idea that the President-Elect Trump has suggested that there'll be some sort of corporate tax relief for pharma corporations will obviously also help to avoid things like companies seeking repatriation in other countries. That’s a significant opportunity for more and better companies to stay in the U.S. and be incented to do so.
Mr. Farrell: We need to see a heightened embrace of digital health among investors and innovators in our industries of therapies, biopharma and medtech, to embrace the future of connected healthcare. It is a real and impactful movement that is instrumental to ensuring patient success and more efficient health management. We’ve seen at ResMed the positive influence that connected-patient engagement tools can have on patient behavior as it relates to staying on therapy, and believe similar results can be seen across both biopharma and medtech industries. We look to our software engineers and informatics scientists to keep developing new algorithms and scalable best-in-class treatment solutions that produce efficiencies for providers, management by exception for physicians, lower costs for payers, and better quality of life for patients.
Dr. Gruber: As the cost of genomic sequencing decreases, the actionable insights we are able to reveal from the human genome grows exponentially. This is leading to huge opportunities for bioinformaticians, who can sift through this enormous amount of data and uncover new insights. For cancer, this could lead to uncovering new targets for drugs or biomarkers that inform treatment, which all help grow potential markets with much more targeted treatments. Also, the FDA is increasingly interested in understanding the mechanism of action of a drug and rationale for treatment, and technologies such as sequencing, bioinformatics, and flow cytometry for immune cells should help provide more information to the agency (giving them confidence to make drugs available earlier) and eventually to practicing physicians.
In addition to generating more data, sharing of this information is important for the growth of the industry and ultimately to growing the clinical knowledge base to make more data-driven research and medical practice decisions. I applaud again the Cancer Moonshot initiative recognizing this as another core tenet. Tocagen is working with patients who have advanced cancer, initially brain cancer, where few treatments are available, and patients urgently await new developments, and for this reason sharing data is a particularly high priority for us.
Recently, Tocagen has benefitted from the generous sharing of data from brain cancer researchers, which has informed development of our lead therapy, Toca 511 and Toca FC. Specifically, data published by University of California, San Diego, and Columbia University, New York, helped identify that the cell population our treatment targets lives at the advancing edge of the tumor. This finding helped drive a cover story in Science Translational Medicine, and media coverage of this study accelerated enrollment in our Phase II/III trial for recurrent brain cancer.
As part of this new trial we are also attempting to validate that patients with this genetic profile are more likely to benefit from our treatment. This one is a modest but important example of how sharing results can fuel the innovation ecosystem and support the development of new disease treatments.