precision medicine


Pharma Stepping Up, Footing the Bill for Genetic Testing & Counseling: Jordanna Mora, Alnylam

It seems to be human nature to value and pay up to hundreds of thousands of dollars for a little white pill that we can drop on the floor--and granted, can do wonders for us, but we want to pay nothing or very little to be told what is wrong with us so that we might know which little white pill to use in the first place.

So let's talk today about the The Alnylam Act, a program to shake up the business model in diagnostics and genetic testing on behalf of patients. The Alnylam Act is what it looks like when a drug company gets proactive and says, hey, we will step in and pay for patients to be genetically tested and counseled for the diseases on which we are working.

“We did this to reduce barriers to genetic testing—and the delays are often pretty long in rare diseases--so that individuals can make more informed decisions about their health.”

That’s today’s guest, Associate Director of Medical Affairs at Alnylam Pharmaceuticals, Jordanna Mora. And just to say it again, you understood her right. Her company, Alnylam, is paying for patients to be genetically tested and counseled.

Is Jordanna hearing any pushback over conflict of interest? After all, the patients who would be testing positive might be candidates for Alnylam’s drug.

The therapeutic we are talking about here is not on the market yet. In theory, it is set to be approved this August, and would be the first of the RNAi drugs. It will be an exciting day for the company, for patients, and for the drug development industry as a new class of treatments is born.

After years of seeing the diagnostics industry struggle to win reimbursement for their innovations, it's refreshing to hear about a drug company filling in the precision medicine gap for the good of patients, many who get misdiagnosed or wait way too long for a diagnosis. Will the Alnylam Act be a model for other drug companies?

“There are a number of companies doing very similar programs, and I think its fantastic,” says Jordanna.

We go for just over 15 min.

Are We Asking Too Much of Genomics in Cancer Research? Tony Letai, Dana Farber

It’s a question we’ve asked on the program before. Are we over relying on the genomics route getting us to biomedical research paradise? Should we be putting more eggs in other baskets?

After combing through lots of clinical trials data, Tony Letai of Dana Farber and the Broad, found that a majority of cancer patients have not benefited from precision medicine. On today’s show he says we need to rethink our approach to cancer research and treatment.

“I think we have a block in our minds in cancer biology about the rules--there are some rules we’re playing by that I don't think we need to play by. I think we can cheat,” he says.

Tony says one of these “unspoken” rules is that we need to use "initial conditions” got from a cancer cell that has been biopsied and killed and broken down for it’s parts, particularly for its “bag of DNA.” Today Tony advocates for an additional approach to genomics, the revival of an older tool, that of screening the live cancer cells against all available drugs. He calls this “functional precision medicine” or a combinational approach, and believes that in 10 years these functional assays will be standard of care in labs everywhere.

Recently we did a show with the CEO of Karius who is bringing sequencing to the world of infectious diseases. What Tony wants to do is bring more of the world of microbiology and cell culture from infectious disease over to the world of cancer treatment.

We have heard of others doing this, as Tony acknowledges. A couple years back we featured Krister Wennerberg from FIMM and last year a private company in Seattle doing something similar. Tony says he has founded a new society to provide network support for this new group called the SFPM or Society for Fuctional Precision Medicine. We finish up at 27 minutes.

A New Method for Long Reads: Hanlee Ji of Stanford on Cancer Genomics Tech 2018

Hanlee Ji is the Senior Associate Director of the Stanford Genome Technology Center as well as an oncologist at Stanford. He’s also a clinical geneticist. In other words, he doesn’t need to take off his glasses and spin around in a phone booth to be able to do about everything.

“I was in fellowship for a long time,” he says in todays interview.

Long reads have been an important theme in the genomics community of late, and Hanlee’s lab recently developed a new method for isolating long fragments of DNA that rivals the long reads of PacBio and Oxford Nanopore. The new method is the first we’ve featured that uses 10X Genomics’ linked reads. The new method also uses CRISPR and CATCH (a new sample prep system from Sage Science), and because it’s done with digital PCR, it offers the nice advantage of only requiring very small sample sizes.

Applications? Hanlee says he’s most excited to use it to identify 're-arrangements’ such as those in congenital disorders or oncogenic drivers.

Hanlee’s lab is also involved in a new clinical trial using precision cancer vaccines that is pulling him headlong into the immuno therapy space.

With a foot deep in the world of genomic technologies and another foot in the clinic, what does Hanlee the oncologist want to tell the technologists? And what does Hanlee the technologist want to tell his colleagues, the cancer docs?

It’s some big questions, and he takes around 27 min to get around them. Enjoy.

March 2018 in Genomics with Nathan & Laura: DTC BRCA and Revisiting All of Us

23andMe steals the headlines yet again.

“If somebody is worried about breast cancer susceptibility in their family, they should certainly not be using this test.”

That’s our monthly commentator and genetic counselor, Laura Hercher, talking about BRCA going DTC. But wait a minute. Then she says the test could be good in some instances.

Fellow commentator Nathan Pearson cracks us up with his new term for the NIH’s All of Us Research Program. We question the big science project after the New York Times reveals that several major institutions, including Geisinger and Kaiser, are pulling out.

It’s Nathan and Laura back to offer their inside take on the lead genomic stories of the past month.

And no matter what, we won’t mention 23andMe again next month. We hope.

Personalized Medicine in the Trump Era with Edward Abrahams

The Personalized Medicine Coalition advocates for a wide group of constituents, including scientists, health care providers, entrepreneurs, payers, and patients. Which is why we’ve often wondered how the organization can be absolutely clear in their priorities.

Today, PMC President Edward Abrahams joins us to answer that question.

For example, take the topic of laboratory developed tests. The country is currently experimenting with an anti-regulatory political direction. Is Ed happy that the FDA has dropped their guidance for LDT regulation? With such a disparate constituency, what does he think is the best way forward? What about the CMS announcement recently that there wouldn’t be any reimbursement for diagnostic tests that weren’t FDA approved (isn’t this at odds with anti-regulatory policies?)—does Ed have any insight here? Also, is the current boom in direct-to-consumer testing a boon or bane for the industry?

When Obama’s Precision Medicine Initiative was launched, many organizations which had been using “personalized medicine” in their nomenclature were pressured to change their names. Ed says he’s still happy with the old term and in fact is working in congress to create the first Personalized Medicine Caucus.

We come in at around 27 min today with one of those unique industry veterans who can talk science with scientists, can talk real with patients, and carries clout on The Hill.

Going Beyond the Liver with RNAi: Chris Anzalone of Arrowhead Pharma

Fifteen years ago, folks in the industry were buzzing about RNAi the way they talk about CRISPR today. Then things went quiet for the technology, at least in the news. Until last year.

In September of 2017, Alnylam Pharmaceuticals, the leader in the RNAi space, announced such positive phase III study results that most experts in the business expect an FDA approval soon. It will be the first for an RNAi drug.

So what took the technology so long, and what was the key to the great results? These are questions we ask today of Chris Anzalone, the CEO of Arrowhead Pharmaceuticals, another runner in the RNAi race. Arrowhead scooped up various RNAi programs from some of the big pharma giants, including Roche and Novartis, during the "quiet" years. Coupling these assets with some of their own technology, they are going after not just some of the esoteric diseases we've come to expect from a new platform first proving itself, but are also targeting the very recognizable Hepatitis B.

How does Arrowhead plan to further differentiate themselves from Alnylam?

“One of our great contributions to the field and, frankly, to world health, is our ability to bring this outside the liver,” says Chris.

So far, the major programs from RNAi companies like Alnylam are all limited to liver diseases. Arrowhead is the first to have drug candidates which go after non-liver diseases. It's a major step forward for this RNAi technology.

How we will know when RNAi has matured, we ask Chris at the end.

Vice Chancellor Keith Yamamoto on UCSF’s Role in Medicine Today

A major chapter in the history of medicine has been written by UC San Francisco. They are writing the next for precision medicine.

Keith Yamamoto is in both chapters. Since the 1970s, he has been a researcher of cellular and molecular biology at UCSF and now serves as Vice Chancellor of Science Policy and Strategy as well. His career has always had these two parallel tracks of scientist and policy administrator. He has sat on various review boards at the NIH and chaired the Board of Life Sciences at the National Academy of Sciences where he worked with a group that would stimulate President Obama to launch his Precision Medicine Initiative (PMI) back in 2015. Today he shares with us what that was like for him.

Though the political wind blows a different direction at the national level these days, the momentum continues for the PMI at NIH, funded, as Keith points out, by congress with the Faster Cures bill for ten years.

And at UCSF? They are just getting started in precision medicine. With an illustrious history in medicine, an enviable location at the tech hub of the world, and resourced to the gills—the university can boast its sixth year in a row of being the top recipient of NIH funds, and rides around the top of the list for private contributions--UCSF is also one of the hosting universities for California’s own Precision Medicine Initiative, which just a few days ago received a huge boost from Governor Brown's new budget.

What is the university doing with all this gold? Keith says UCSF is building a machine, a precision medicine platform, that brings together data from all the disparate places we’ve talked about here on the program—the omics data, wearables information, electronic health records, etc—into an information commons similar to Google Maps, creating a "knowledge network." It’s a story we’re all familiar with, and if anyone can do it, certainly this is the place.

In addition, Keith describes one of the many collaborations UCSF is involved in called ATOM, or Accelerating Therapeutics for Opportunities in Medicine, a public-private consortium that brings the idea of big data sharing to drug discovery at the pre competitive level.

“What we’re moving is the starting line, rather than the finish line", says Keith.

The NIH has spearheaded similar efforts before. Perhaps with UCSF’s star computer science power this effort will go new places.

For those in our audience attending next week’s Precision Medicine World Conference in Silicon Valley, you can hear Keith talk on Accelerating Cancer Therapies and Exploiting Longitudinal Patient Data: Partnering to Achieve Precision Medicine.

Seattle Startup Takes Precision Oncology to the Next Step: Carla Grandori, CEO, SEngine

Carla Grandori was for thirty years a cancer researcher most recently at the Fred Hutch in Seattle. She had her personal reasons for working on cancer, she tells us in today’s show. Now, she’s the CEO and founder of SEngine, a startup offering something completely new for oncologists around the country.

Carla says she was motivated to step out of the research lab when two patients came to her personally and asked her, “can you study my cancer?”

“When I heard that second request, a light went off. I had thought maybe in 10 years the research would be useful. But then this patient made me think, ‘no, I think we can help now.' When I realized the potential of our technology to help patients immediately, I saw no more boundaries. I said, 'we have to get there.’"

What is this technology? And if it’s so powerful, why hasn’t it been offered before?

SEngine's (think Search Engine) new test, called PARIS, screens individual patient tumor cells onsite against a complete library of over a hundred and fifty cancer drugs. Before now with say, Foundation Medicine, there has been much progress in sequencing tumors and offering lots of omics data virtually. But the PARIS test goes a step further, screening a patient’s actual cells in real time while also combing through accompanying omics data. Until now we didn’t have the technology to deal with the samples with enough precision and in small enough quantities, nor the necessary robotics and software.

The company received CLIA certification back in June and the test is for sale to oncologists now. The next step for SEngine is to build up a major clinical utility validation.

Immuno Oncology 2017: Looking Back, Looking Forward with Rachel Laing and Olivier Lesueur

Immuno oncology is now the dominant topic at Mendelspod. From shows with CEOs presenting new panels of predictive biomarker tests, to the firsts at the FDA with the CAR-T approvals as well as the first approval of a drug (Merck’s Keytruda) based on a common biomarker (MSI) rather than on a tumor type, to scientists discussing rare cells of the immune system, we had more podcasts on this topic than any other in 2017.

Rachel Laing and Olivier Lesueur are partners at Bionest, a global life science consulting firm. They work with companies on both the drug and the diagnostic sides of immuno oncology and are at ease switching back and forth between the two in today's discussion.

Complexity is the key word, says Rachel. Immuno oncology has turned the development of biomarkers on its head. Whereas formerly with a simple companion diagnostic, one starts with a very specific biomarker develops from there.

“With immuno oncology, it’s very different from that,” she says. "You’re not just dealing with a tumor cell and the signaling that goes on there, you’re dealing with the immune system. And there’s a lot of interplay between the tumor, the microenvironment, and the immune system. It’s unrealistic to think you could get away with just measuring one biomarker.”

What are the challenges for diagnostics companies in commercializing various biomarkers into ongoing testing for the same patient, or what’s becoming known as “real time oncology?”

Olivier addresses the great reimbursement irony in the field of drugs and diagnostics. Without the biomarker tests, the drugs may not work for the right patients. Yet the diagnostics companies receive pennies while the drug makers are getting away with— well, we all know that issue. Olivier says one drug maker recently preempted this problem by offering to just pay for the diagnostic up front in geographies where the diagnostic reimbursement was being questioned, which is good for everyone, including the patients, and shows some vision. This problem of undervaluing diagnostics has bedeviled our industry for a long time and becomes especially crucial with immuno therapies that rely on patient stratification and ongoing profiling.

In our final question about what we’ll see in the year ahead, it’s cautioned that though patients are seeing more and new therapy options, the complexity of treatment is becoming ever more demanding on some people who are already pretty sick.

Huh? 30 Million Americans Have a Rare Disease? Howard Jacob on the State of Clinical Sequencing

Here’s a title for you. Chief Genomics Officer. Today’s guest is also the VP of Genomic Medicine and a faculty investigator at the HudsonAlpha Institute for Biotechnology.

He launched the world’s first genomic medicine program becoming the first person in history to use genome sequencing to diagnose, treat, and cure a patient. Few people exude the sheer force and vision for the future of genomic medicine that comes from Howard Jacob. We’re very pleased to have him on Mendelspod for the first time to talk about progress with rare disease, sequencing technology, and how he would teach genomic medicine to young people today . . . And of course, that genomic age old question: the exome or the whole genome?



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