As part of his proposed budget, President Barack Obama recommended spending $215 million on a Precision Medicine Initiative. (See BioWorld Today, Feb. 2, 2015.)
"We shouldn't just celebrate innovation. We have to invest in innovation. We have to nurture innovation. We have to encourage it and make sure that we're channeling it in ways that are most productive," Obama said in a press conference announcing the initiative.
Most of the money will go to the NIH. There's $130 million to recruit and track a million or more volunteers willing to share their genetic and clinical information to try and link the two.
"If we have a big data set, a big pool of people that's varied, then that allows us to really map out not only the genome of one person, but now we can start seeing connections and patterns and correlations that helps us refine exactly what it is that we're trying to do with respect to treatment," Obama said.
Another $70 million is slated for the NIH's National Cancer Institute (NCI) to help identify genomic drivers in cancer and use that knowledge to develop drugs to fight tumors with those specific mutations.
"We want to find the genetic factors that can lead to cancer. And we want to use that knowledge to develop new and more effective approaches to help people beat this disease," Obama said.
There's also $10 million earmarked for the FDA to help the agency acquire additional expertise and advance the development of databases that can help the FDA understand precision medicines as they come up for regulatory review.
The final $5 million will go to the Health and Human Services' Office of the National Coordinator for Health Information Technology (ONC) to help databases interact with each other while ensuring that the data is kept secure.
BENEFIT BY ASSOCIATION
Despite the lack of a direct benefit from funding of the Precision Medicine Initiative, industry players are excited about the presidential support.
And there's certainly some evidence that government investment in science can trickle down to the private sector. Obama cited a study that found that "every dollar we spent to map the human genome has already returned $140 to our economy."
"The biggest impact of the president's initiative is to shine a light on the promise of precision – or personalized – medicine over the next five years," Keith McCormick, Trovagene Inc.'s vice president of sales and marketing, told BioWorld Insight.
San Diego-based Trovagene has developed tests for monitoring cancers with liquid biopsies, allowing physicians to detect the three Rs: whether patients are responding to treatment, when their tumors arerecurring, and whether they're developing resistant mutations that will make their treatment stop working.
Trovagene has two tests that use circulating tumor DNA to monitor mutation loads. One test detects the presence of a BRAF V600E mutation. Melanoma with a BRAF mutation can be treated with Zelboraf (vemurafenib, Roche AG) or Tafinlar (dabrafenib, Glaxosmithkline plc). A second test looks for mutations in KRAS, which can be predictive of poor response to certain cancer drugs.
NCI's initiative should benefit Trovagene in the long run since the company is dependent on the identification of actionable mutations and the eventual development of precision medications to treat tumors with those mutations.
Trovagene is developing another test in anticipation of the approvals of Clovis Oncology Inc.'s rociletinib and Astrazeneca plc's AZD929, which are both designed to treat non-small-cell lung cancer (NSCLC) with a T790M mutation in EGFR that makes the tumors resistant to other EGFR inhibitors such as Tarceva (erlotinib, Roche AG and Astellas Pharma Inc.). "Our EGFR/t790 mutation test will be out and available before the drugs are available," McCormick said.
FROM TUMOR TYPE TO GENETIC TYPE
Scientists have come a long way from developing cancer drugs to treat tumors based on their tissue of origin to treating based on the genetic makeup of the tumor.
"It was hard to get people interested in sequencing cancer," Charles Baum, said of his time at Pfizer Inc. developing Xalkori (crizotinib) a decade ago.
The president shining a spotlight on precision medicine should take the field to the next level, helping patients understand the issue. "You get more people to understand that there is a lot of heterogeneity in cancers," Baum said. "It helps push the system in the right direction even if the physician isn't thinking about it."
Baum is continuing his work on precision medicine as president and CEO of Mirati Therapeutics Inc., which has three oncology drugs in the clinic.
Mocetinostat, a histone deacetylase inhibitor, is in phase II trials in bladder cancer, diffuse large B-cell lymphoma (DLBCL), and myelodysplastic syndrome. The trials for bladder cancer and DLBCL are selecting patients with mutations in CREBBP and EP300, a pair of proteins involved in histone acetylation, which Mirati hopes can be counteracted by inhibiting histone deacetylase. The phase II data from the trials should be available midyear.
The San Diego-based biotech also has MGCD265, a tyrosine kinase inhibitor that's specific for MET and Axl. Activating mutations in both genes have been seen in NSCLC and head and neck cancer. Mirati expects to have data form a phase Ib trial in NSCLC selected for genetic alterations of MET or Axl in the middle of the year.
Mirati has another kinase inhibitor that is specific for a closely related spectrum of tyrosine kinases, the Trk, RET and DDR families. MGCD516 is in a dose-escalation phase I trial in NSCLC patients with driver mutations.
While MGCD265 and MGCD516 both treat NSCLC, the spectrum of patients won't overlap. MET and Axl driving mutations are seen in 8 percent of NSCLC, while activating mutations in the Trk, RET and DDR families are found in a different 5 percent.
TOO MUCH DATA?
The lower cost of sequencing has made Obama's 1 million volunteer data possible, but it's introduced another problem: how to process all those data.
"There's an unprecedented amount of data that is being generated," Pieter van Rooyen, CEO of Edico Genome Inc., told BioWorld Insight.
San Diego-based Illumina Inc.'s new HiSeq X Ten has a run cycle of about three days and produces about 150 genomes each run cycle. To avoid a backup of data, the sequences have to be aligned before the next run is complete, giving the computers about 28 minutes to complete each alignment. The typical server requires about 24 hours to do the computation, requiring at least 50 servers to complete the computation.
Edico Genome, of San Diego, has developed a processor card called Dragen that fits into a slot in a server or PC, which can process one genome in about 25 minutes, doing the work of 50 servers.
While speed is important for avoiding data pileup, it will also be useful for clinical applications as more disease-causing genetic variations are developed and genomic sequencing becomes a routine diagnostic tool.
"Our product will become absolutely essential in the diagnostic market," van Rooyen concluded."
