commercializing diagnostics


Why Childhood Cancers Need Their Own Gene Panel: Tim Triche

When we first talked with Tim Triche of LA Children's Hospital, we found out he was a bit of an outlier among cancer researchers. He was an advocate for poking around in the non-coding RNA.

Today we welcome Tim back to the show to talk about a new gene panel that he has designed specifically for childhood cancers. It’s a first of its kind and was modeled quite closely on the gene panel for the NCI’s MATCH trial. The new panel has both a DNA and an RNA component, and the RNA side is by far the biggest.

"There are 1,400 different amplicons on this panel looking for RNA fusions. Thermo Fisher tells me it’s the most ambitious RNA panel that they’ve ever undertaken," Tim says in today's interview.

"When 100 cancer patients walk in your office, then 100 cancer patients walk in your office," says Tim, quoting a common line in the field that points to the uniqueness of every cancer.

Yet even though every cancer is different, certain biological commonalities combined with better sequencing tools is enabling the design of new gene panels to guide in diagnosis and treatment. More and more a cancer is looked at based on the drug that might treat it rather than the organ in which it grows. The new panel can guide this treatment.

Some of the most important targets on the panel are RNA fusion transcripts. What are they, and why are they so important for helping kids?

Childhood cancers come from inherited mutations, whereas most adult cancers have to do with the skin or the linings of the organs due to mutations caused by environmental impacts. Fusion transcripts are very common in the youth cancers and have been a big part of routine diagnostics.

If a mutation is there early in life, is it likely to turn into cancer sooner rather than later? Yes, says Tim.

“If you look at the incidence of childhood tumors, there’s a big bump in the first months or year or two of life, and then they disappear thereafter."

Additional benefits from these new next gen sequencing panels are that they can work with very small “real world” samples of tumor tissue, and they can also be used as discovery tools. Tim says the panel, called OncoKids, is ready to go for frontline therapy, and is hoping to get the word out to oncologists everywhere.

August 2017 Review with Nathan and Laura: CAR-T Cashes In, Embryos Edited in US, and the Invitae Incident

Back from summer vacation, Nathan and Laura are smoking hot as they look back over some exciting headlines.

The summer boiled over with plenty to talk about, but it was just this week that delivered most of the news for our discussion today. Novartis’ gene therapy based on CAR-T technology was approved Wednesday, making it the first gene therapy to be approved ever in the US. Analysts will be trying to figure out how high high is when it comes to the price tag, but Nathan and Laura explain why this therapy is a big deal for patients.

As for the first gene editing of embryos in the US that happened earlier in August? Nathan says, yes, it’s a first, but the big story is how "strikingly reliable the CRISPR edit is in germline vs the rest of the body."

Finally, we heard a few days ago that genetic testing provider, Invitae (recently featured here on the program) had sent out a large batch of false negative tests. Laura, a genetic counselor, says that in the absence of FDA regulation the system is operating on trust.

“And I want to say,” she adds, “ I trust Invitae. They’re a good lab, and I think they’re handling this well.”

 

Thermo, Pfizer, and Novartis Pull Off a First for NGS in Lung Cancer

Today we get to bring you a feel good story, one of the major achievements so far in precision oncology. Three large companies—Thermo Fisher, Pfizer, and Novartis—put aside their differences to come together for patients.

The patients are those who suffer from non-small cell lung cancer. In June, the FDA approved for the first time an NGS panel with multiple genes for multiple drugs that treat this kind of cancer.

“It’s groundbreaking for patients, because instead of having to wait for a hierarchal testing approach to their cancer, this one test could be able to give the answer for the patient."

By hierarchical, Annie Martin, the VP Global Head of Precision Medicine at Novartis, means the usual stepwise approach to testing for patients with this cancer. Typically patients are tested for first EGFR, followed by ALK, followed by ROS1, followed by BRAF. Now, thanks to a new NGS panel out by Thermo, all of these tests will be done at once and has been approved for various therapies.

In addition to Annie, we’re also joined by Thermo’s Joydeep Goswami, President of Clinical Next Generation Sequencing and Oncology at Thermo Fisher and by Hakan Sakul, VP of Diagnostics at Pfizer to talk about their collaboration.

How did Thermo decide on this panel, and what possible future uses to do they see? And how did the three large corporations—one diagnostics and two pharmas--come together to pull this off?

Join us with three of the industry’s leaders as we uncover the work behind a major milestone for precision oncology.

Making Genetic Testing Mainstream Medicine with Sean George, Invitae

Invitae appointed their co-founder Sean George as CEO earlier this year. He joins us to share his bold vision for the field of genetic testing.

Sean mentions the word “scale” several times in today’s interview. Invitae was by no means the first on the scene, beginning in late 2013 (just after the Myriad Supreme Court decision), but with plenty of funding and talent they have sought to push the needle forward in a big way when it comes to genetic tests. The company has always exuded the message that there is all this valuable genetic information available now, and it’s just not getting to people who could benefit.

Sean says that this urgency is what drives him in a quest to “prevent unnecessary suffering that exists today by tearing down the barriers that are keeping this powerful and fundamental information from benefiting people’s lives.”

What are the barriers? Sean says cost is number one. That there are many out there who would buy genetic tests but can’t because of the price. In an age of astronomical drug prices, is it really that crucial to squeeze off a few dollars from a genetic test? And how does Sean and Invitae make the decision when to offer a test?

While Invitae has not gone the direct-to-consumer (DTC) route, Sean says they have a bit of a hybrid model where they market directly to consumers, but sell only into the clinic.

Sean agrees that the industry has had some “whiplash”, moving forward with excitement only to have big set backs. He says that in his company presentations, he likes to show two New York Times headlines:

The first goes, “10 Years after the Human Genome Project, What Does It Matter?” And the second headline taken from 1991: “Personal Computers: So Who Needs Them Anyway?”

Need Better Standards for Your Clinical Assays? NIST Can Help

The life science tools space is flourishing. Biomedical research output is at an all time high. Today’s guest says there are over 40,000 papers published each year on cancer biomarkers.

But very few of those become commercialized tests. Why?

Many had hoped the FDA would step in and save the diagnostics industry from itself, from a race to the bottom when it came to being able to reproduce clinically relevant tests. But that’s obviously on hold. In the meantime, others are stepping in. And there is one government agency which has no regulatory authority but some power to help out.

Kenneth Cole is the group leader for developing bioassay methods and standards at the National Institute of Standards and Technology. His group has just created a new set of standards and methods for HER2 testing which is available to the clinical lab community to help improve their own assays. It’s been said on the program that this very common test for use in cancer therapy has a false positive rate of 20 percent. That's too many patients getting told the wrong thing.

Ken’s group is now going to work on EGFR and other common tests, and they can help the testing community in several ways. First of all, Ken says, they have a “the luxury of being able to focus in on the measurement techniques and on examining all the sources of variability in an assay." They also work on characterizing cell lines, which have become “an essential part of modern biology.” Ken says a big part of the work at NIST is the education of the community and of the new crop of scientists.

Do you have an assay you’d like help with? Ken is easy to reach, and NIST welcomes your requests. They have set up many partnerships from loose collaborations to projects with IP protection.

Often the best place to find solutions is in going back to the basics.

Turning on Your DNA with Justin Kao, Helix

They’re getting a lot of buzz this week. We’re pleased to have Justin Kao, a co-founder of Helix on the program today for the first time.

Launching formally yesterday, Helix has generated a good amount of enthusiasm—in no small part because they raised $100 million and are backed by Illumina. And the Helix business plan is definitely a bold one. They aim to become the DNA testing platform that supports and partners with direct-to-consumer (DTC) and clinical apps, offering genomic tests that are both medical and non-medical. Helix's part is to collect the samples, do the sequencing (exome plus), and be the app hosting platform.

23andMe co founder, Anne Wojcicki, said once on this program that “DTC testing is a whiplash culture.” This year, with a lighter hand at the FDA during the Trump administration when it comes to genetic tests, entrepreneurs are showing more boldness. This is one of those leaps forward.

“Consumer interest in DNA is exploding,” Justin says today. “The genealogy industry itself has been doubling every year for the past few years.”

Justin lists some of the app partners with which they are launching, and says they will soon be adding more, including a partnership with the clinically focused, InVitae. He says Helix has a CLIA certified lab and has been working with the FDA since they began.

Is there an inherent conflict in the attempt to host both medical genomic tests—such as the 59 ACMG recommendations--and tests that help us pick the right scarf or wine? According to the vision of Helix, DNA is DNA.

Justin compares the Helix platform to the basic enabling technology of GPS.

“What if I said to you, I’m going to the gym, and I’m going to do my standard 30 minutes on a treadmill because that’s what everyone does? In a few years, you’re going to turn to me and say, ’well that’s odd, your body and my body are different. Don’t you turn on your DNA?'"

Move Over PDL1: New Test Combo Adds RNAseq to Better Track Immune Escape

Reports from ASCO, the nation’s biggest cancer conference, this year again were full of stunning stories about the success of older and new immuno therapies. The race has never been hotter for biomarkers to target patient groups. Most of this new class of drugs--which harnesses the immune system to go after the cancer--inhibit an immune checkpoint called programmed cell death protein 1 or PDL1. So frontline cancer treatment these days typically includes a test for the PDL1 biomarker. But there are a breadth of potential targets in the immune system that promise to make this class of cancer drug even more effective.

Today we talk with Mark Gardner, CEO of OmniSeq, who has just received approval from New York State (the company is in Buffalo) to launch their new Immune Report Card.

“The biology is complicated. Even for folks that are PDL1 high, in the majority of cases those patients are not going to respond to these drugs. The average number of responders is 20-30%. So we know something else is going on. It turns out we’ve known some of the mechanisms for how the tumors are achieving "immune escape.” What we’ve not had the ability to do is to simultaneously measure across the range of hypotheses for how that tumor is escaping."

Omniseq's Immune Report Card includes mutational burden and MSI testing, which is common practice today. The two additional “legs” of the report are copy number variation for PDL1 as well as RNAseq.

The Last Major Disease To Be Studied? Ron Davis of Stanford Thinks So

Let’s say you’re a biomedical researcher looking for a place to make your mark. You find out that there is still a major disease that affects more than 2 million people in the US, and we still know virtually nothing about this disease at the molecular level. Wouldn't that stand out?

It certainly has to today's guest, Ron Davis, who is also a father searching for answers for his son. Ron has been the Director of the Stanford Genome Technology Center for decades. He collaborated on the first DNA microarray and made a major contribution to the Human Genome Project. For five years now, Ron has directed his comprehensive skill set in bioengineering--and his vast connections--to work on a cure for ME/CFS, or Chronic Fatigue Syndrome, a disease which has ravished his son, Whitney Dafoe.

With no funding from the NIH so far (he says they're not good at starting things), Ron is working to characterize the disease at the molecular level. A new device developed at his center that he calls a "nano needle" could enable the first definitive diagnostic test for patients with CFS.

The history of this disease is of patients desperate with hope but always facing a major stigma. Many medical professionals are still not on board with diagnosing a patient with CFS. Ron says this stigma and lack of interest by the research community has created a big chance.

“This is a tremendous opportunity. Here’s a major disease which at the molecular level you don’t know anything about. This has got to be the last disease like this."

Find an extensive recent written interview with Ron here.

Grail Merger, Genomic Autopsies, Overtreatment Alarm, and Controversy at Ancestry.com: May 2017 Review with Nathan and Laura

Is Grail already merging? Genomic autopsies? Does the House's new healthcare bill turn mere genetic risk into pre-conditions? Nathan and Laura are back to find meaning in the rush of May's headlines.

Laura cites a disturbing survey of over 2,000 women diagnosed with breast cancer that found half of them had unnecessary double mastectomies after genetic testing. She says unabashedly, “In big letters, it’s an ADVERTSIMENT FOR GENETIC COUNSELING.”

Speaking of alarms, Nathan says attorney Joel Winston’s blog against Ancestry.com’s terms and conditions was fear mongering.

We end with comments on the passing of one of the creators of the orphan drug industry, Henri Termeer.

Is Population Medicine Failing Us? Michel Accad

Is health the same thing for an individual as it is for a population? This question goes to the foundation of how we practice medicine today and that of most of genomic research.

Michel Accad is a cardiologist in San Francisco and the author of a new book, Moving Mountains: A Socratic Challenge to the Theory and Practice of Population Medicine, in which he uses Socrates to spar with Geoffrey Rose, a British physician and one of the architects of modern medicine.

As early as the 1950’s, Rose advocated for the idea that individuals should be treated based on bell curves of an entire population, essentially risk based medicine. This philosophy would lie at the heart of not only the British National Health Service but many public health programs. It informed the famous Framingham studies here in the U.S. In fact, the term “population medicine” is a very positive term for those working in healthcare today. Genomic medicine has been an outgrowth of population medicine.

Michel says this philosophy is failing us at the level of individual health. Third party payers, be they governments or insurance companies, are in their offices working a system based on large datasets. They develop algorithms using all kinds of risk studies. But these payers have little to no contact with the actual patients. Ironically, he says, we call it personalized medicine. Michel points to hypertension, a disease area where sixty years after Rose pushed for risk studies, cardiologists are still divided into camps over whether to treat a patient if their blood pressure lies above the average. Michel argues that population medicine is utilitarian and ultimately utopian. What are framed as scientific studies are really social engineering.

What about clinical trials, we ask Michel. Don't population studies bring doctors and patients many good drugs?

In the second half of the interview, Michel points out that a mechanistic view of biology dominates clinicians and scientists today. It’s true. Our guest last week, a well known geneticist from Stanford, compared people to cars, arguing for the need to wear health data gathering sensors.

"Right now among philosophers of science, there’s a recognition that “mechanism” is inadequate to explain cellular organisms."  The study of biology also has often been developed with tautologies, he says.  "For example, say you’re studying the beaver and you ask what is a beaver. The standard answer is to go to the genetic sequence. From the genetics, you say you have a beaver. But you have to know what beavers are in the first place in order to study a beaver. It’s a circular argument."

So what other models might we use in biology? And what can we do in healthcare if we’re not using large population studies--go back to blood letting?

(Amazon link)



New to Mendelspod?

We advance life science research, connecting people and ideas.
Register here to receive our newsletter.

or skip signup