Interview with Kevin Hrusovsky part 2: next generation sequencing

Rebecca Aris interviews Kevin Hrusovsky

PerkinElmer Inc.

As part of our personalised medicine themed month we interviewed Kevin Hrusovsky. In this, the second of a three-part interview, Kevin discusses next generation sequencing.

(Continued from Interview with Kevin Hrusovsky part 1: molecular interactions of a disease )

In part one of this three-part interview, Kevin Hrusovsky highlighted some exciting recent advances in the understanding of molecular interactions of diseases.

In the second part of his interview, Kevin discusses next generation sequencing (NGS) and the role it plays in improving patient outcomes.

Interview summary

RA: What role does next generation sequencing play in improving patient outcomes?

KH: Many in the medical community are excited about the potential, and are rapidly trying to figure out how to harness the technology to improve patient outcomes.

Exome sequencing (that is, the protein-coding part of the genome) has already demonstrated promising utility in the clinical setting for diagnosing diseases. Companies and Medical Centers such as Illumina, Expression Analysis, SeqWright (part of GE Healthcare), Foundation Medicine, Massachusettes General, Dana Farber, Childrens Mercy Hospital in Kansas and Ambry Genetics have achieved CLIA certification in their labs, and many others are following suit.

The most addressable diseases include cancer and rare genetic diseases:

In cancer, NGS can provide rational selection of targeted therapies based on the precise molecular pathways disrupted in an individual patient’s tumor and also to monitor the evolution of the tumor in response to these treatments. Sequencing gene sets is already being used to guide cancer treatment. In addition, it’s a powerful tool for patient stratification. A high profile study from the Michigan Center for Translational Pathology, Ann Arbor, demonstrated that NGS could be translated effectively for biomarker trials for personalized oncology. They showed that NGS could be used to identify patients who could benefit from a candidate drug, enabling them to use NGS for effective patient stratification.

In addition to cancer, we are seeing the adoption of NGS in the newborn setting, where the clinical benefit can be very compelling. Babies can be screened by NGS to detect all Mendelian (inherited) disorders at birth – there are currently ~3000 known disease genes that fall into this category. These rare genetic disorders account for 17% of pediatric hospitalizations and an even greater proportion of healthcare costs. These diseases are devastating and often hard to diagnose based on symptoms alone so NGS is a tremendous tools that can help address this issue. We have already seen a number of examples where NGS has uncovered rare genetic life-threatening diseases in children, allowing life-saving intervention. However, until now, the logistics have been problematic because the time to generate NGS data and use it to make a diagnosis is often too long to be useful in a critical newborn setting, where timeliness can mean the difference between life or death. Also, the cost of genomic sequencing has simply been prohibitive in most cases. Fortunately, a tremendous breakthrough was made in recent weeks by a group from the Children’s Mercy Hospital in Kansas – they developed an impressive streamlined “automated medicine” system that can sequence a severely ill newborn baby’s genome and deliver the verbal diagnosis within 50 hours, which is fast enough to enable the physician to make a potentially life-saving treatment decision. What’s more, they achieved this amazing feat in a cost-effective manner – over six hundred diseases can be screened for just $13,500 per newborn genome, which is less than the cost of two nights in the neonatal intensive care unit.

As these NGS success stories grow in number and scope, we are seeing physicians, patients and families wanting access to this important medical tool, and we are seeing a rapidly growing number of Centers offering NGS. For example, two large-scale clinical sequencing programs were launched in Jan 2012,one at Baylor College of Medicine in Houston, TX, and the other at UCLA, and many others are following suit. NGS is well on its way to becoming part of mainstream medicine – and given how quickly things have evolved so far, that day may be much closer than we can envisage.


“…we are seeing a rapidly growing number of Centers offering NGS…”


RA: What is needed to drive adoption of next generation sequencing?

KH: Cost of sequencing: sequencing a patient’s complete genome can cost as little as the total cost of tests that target specific genes. However, we need to get the costs down even further to achieve a compelling cost-to-benefit ration that payers cannot ignore.

Improved sample preparation: samples sizes continue to get smaller as physicians continue to search for less invasive sampling techniques, i.e., tissue tumor biopsies are slowly being replaced by more frequent fine needle aspirate sampling and longer-term may be replaced by circulating tumor cells blood testing. In addition, given the explosion of new molecular tests, more testing per sample is rapidly driving the need to run many tests simultaneously (multiplexing) on smaller samples. All of this is requiring more from less and is putting considerable pressure on platform sensitivity and precision. Our technologies are designed for multiplexing, precision, sensitivity and efficiently automating sample preparation methodologies.

Availability: at present, more than 25 companies in the US compete in the NGS services market. Given double digit market growth and the huge market potential in clinical sequencing, many more companies are expected to enter.

Clinical effectiveness / outcomes: the industry will have to demonstrate to the larger medical community that having NGS results in hand can help improve the health of their patients. In a handful of cases to date, sequencing a patient’s genome has led to a life-changing diagnosis.

Cost saving effectiveness: reduced healthcare costs, better use of healthcare dollars.

Reimbursement: while single gene sequencing is typically reimbursed, and whole-exome sequencing (WES) is sometimes reimbursed, this is still somewhat ad hoc and needs to be more standardized and routine. Whole genome sequencing (WGS) is not reimbursed at this point, and providers will need to convince payers that the cost-to-benefit ratio makes sense relative to WES. As more physicians and patients call for NGS, payers will have to develop policies that treat NGS as a clinically important – and often essential – service.

Standardization and quality control: currently there are no national standards in place in the US (let alone outside the US), which means that the nature and the quality of the data can vary from lab to lab. Standardization and uniform QC would increase credibility and reliability of the data, and hence physician confidence, which in turn should help drive adoption.

Regulation: the FDA does not have a regulatory pathway in place for NGS, and there are currently no precedents. The FDA and gene test / NGS providers will need to work together to forge a path that results in NGS tests that are safe and effective, yet are not overly onerous or costly.


“…the FDA does not have a regulatory pathway in place for NGS…”


RA: How can we drive acceptance of personalized medicine?

KH: Demonstrating (1) clinical utility and (2) ability to scale to address entire healthcare systems.

Ensuring privacy of genetic data, especially genetic risk information.

Demonstrating the ability to address fundamental problems facing medicine: For example, there is widespread concern that FDA-approved medications are the fifth leading cause of death in the US, and that adverse drug events are responsible for half a million serious injuries and hospitalizations each year. The good news is that many of these events could have been anticipated and prevented by pharmacogenomic testing – these are typically simple DNA tests. Ideally, these tests should be implemented systematically across the healthcare system so that they become a routine part of medicine, rather than thought of as some esoteric “nice to have.” Bottom line: using pharmacogenomic testing as a pre-emptive strategy will save lives and save on healthcare costs.

Providing easy access to information that is easily understood by all, especially the patient. Thanks to the internet, patients are educating themselves as consumers, and are being more proactive about their health and medical treatment. The more mainstream that personalized medicine becomes, the greater its acceptance.

We are already seeing an appetite for personalized genetic information in the form of direct-to-consumer (DTC) genetic testing. Over the past 2 years, the FDA has been meeting with DTC companies to figure out how to make these products legit in the eyes of the FDA. In June 2012, 23andMe, the most high profile provider of personal gene tests, filed a 510(k) for FDA clearance for a DTC test – this is an industry first. What’s more, the Company expects to submit ~100 or more 510(k)’s to the FDA by the end of the year. These include tests that reveal whether or not someone has inherited a disease mutation as well as pharmacogenomic tests that predict drug response. Once DTC tests are approved, it opens up the tremendous opportunity of personalized health, driven in large part by the public’s desire for tools to improve their own health – a great example of self-motivated preventive health.

Increasing the number of therapeutic options for each disease, since each treatment will work for some – but not all – patients. For personalized medicine to be widely adopted, there should be the promise of a hopeful outcome for all, not just a lucky few.


“…using pharmacogenomic testing as a pre-emptive strategy will save lives and save on healthcare costs.”


Therapeutics for a broader range of diseases: currently there are many diseases for which no treatments exist, so there is little impetus for knowing the underlying genetic cause of a disease if the information is not clinically useful. The “peace of mind” argument is weak, and some might argue that knowledge of a problem without a solution actually destroys peace of mind.

Educating and enabling individuals to understand the power and availability of personalized medicine tests, such that they actively seek more information from their healthcare providers. The medical profession is traditionally responsive to the needs of their patients, so will be more likely to accept personalized medicine if their patients demand it (of course, it goes without saying that the scientific / clinical validation data must be in place).

According to a recent study (“DTC genomic testing: systematic review of the literature on user perspective”), there is indeed public interest in DTC genomics tests – consumers are often anxious about the nature of the results, and they prefer to access and discuss genomics tests with their healthcare professionals. Again, this will motivate the medical profession to become actively engaged in personalized medicine.

The next part of this interview can be viewed here.


About the interviewee:

Kevin Hrusovsky was appointed President, Life Sciences and Technology, Perkin Elmer in November 2011, following the acquisition of Caliper Life Sciences. In addition to leading the Life Science segment of PerkinElmer, he is also responsible for Services for LST products and Informatics, which was recently moved into LST.

The union of PerkinElmer and Caliper brought together many innovative technologies which, when combined, offer what Hrusovsky believes is a remarkably comprehensive and disruptive portfolio that enables translational medicine and personalized health.

A key part of the mission at LST is to revolutionize global personalized health by facilitating early detection, next generation treatment and ultimately prevention. Importantly, given PerkinElmer’s long track record as a leader in environment health, the Company’s view that helping to sustain the earth’s ecosystem is integral to our goal of preventing and eradicating disease. As part of the drive towards personalized health, earlier this year PerkinElmer announced a new initiative – the creation of Centers of Personalized Health Innovations (cPHI). The first cPHI facility is currently being built in Hopkinton, Massachusetts, and is scheduled to be complete by mid-2013. Through these Centers, PerkinElmer will be able to leverage our innovative strengths in imaging, microfluidics, next generation sequencing, biotherapeutics, epigenetics, companion diagnostics and informatics, with a focus on enabling.

What role do you think next generation sequencing plays in improving patient outcomes?