NEW YORK (GenomeWeb) – The Molecular Evidence Development Consortium (MED-C) — a non-profit trying to establish standards for next-generation sequencing and enhance the evidence base around personalized medicine — has received funding to launch its first registry in non-small cell lung cancer.
Thermo Fisher Scientific, Illumina, Eli Lilly, Celgene, and Roche/Genentech have committed their expertise and an unspecified level of funds for MED-C to build a registry of lung cancer patients who will have their tumors profiled on research-quality, standardized NGS panels. Based on the molecular characteristics of their tumors, patients in the registry will receive standard therapies, including on- and off-label treatment options supported by guidelines and in drug compendia. Participating doctors will report patients' de-identified outcomes into MED-C's database, which drug companies, labs, payors, regulators, and healthcare providers can use to learn more about molecularly informed treatments pathways.
MED-C will also direct patients with certain markers to precision treatment studies, such as the government-sponsored NCI-MATCH trial and Lung-MAP. "We're focused on getting the registry off the ground, establishing the relationships with the payors, and building strong affiliations with the big trials taking place," MED-C CEO Dane Dickson told GenomeWeb.
Since MED-C's focus is building registries, it will not facilitate access to off-label, off-compendia drugs — in other words, treatments that are not part of the standard of care and not supported by guidelines — because that would require institutional review board approval as a clinical trial. With trials like NCI-MATCH and numerous others, "there's no reason to compete," Dickson said. However, he noted that MED-C will work with NCI and academic centers to launch further basket trials or future single-arm Phase II trials based on the advice of its expert groups.
The aim of MED-C is to "enhance clinical trials and the standard of care," Dickson said. "We're trying to address unmet need … in the initial upfront diagnosis, when a physician doesn't know what test they're ordering and the results they're getting. We're trying to define that in a way that helps them care for patients."
Dickson was previously director of clinical science at MolDx, the Centers for Medicare & Medicaid Services' program for establishing coverage and payment for molecular diagnostics based on evidence evaluations. In that role, he got a firsthand look at how precision medicine is challenging different groups in the healthcare system.
Drugmakers, unable to conduct traditional randomized studies on exceedingly rare biomarker-defined populations, need new clinical trial approaches to evaluate therapies. Labs have powerful platforms that can analyze patients for many markers at once, but these tests employ different analytical and interpretation methods that can't be easily compared. Physicians want to give their patients precision care, but can't be sure that insurance would cover genomic testing or off-label treatment modalities. Regulators need new ways of evaluating precision drugs that are increasingly co-developed with complex diagnostics and are concerned about the lack of oversight of marketed lab-developed tests (LDTs) used to guide treatment strategies. And payors, seeing an influx of advanced molecular testing being performed, have limited ability to determine if these interventions are medically necessary and evidence-based.
MED-C, if successful, could disrupt how all these players currently operate. Its first attempt to do so will be with the N1N Registry, which newly diagnosed non-small cell lung cancer patients can join to receive standard treatments informed by their tumor markers and have their de-identified data stored in an open-access database.
The information in this database can help pharmaceutical firms pinpoint new leads for drug development, diagnostic developers gather data on whether a particular testing strategy is improving outcomes, and researchers improve their understanding of disease states. The US Food and Drug Administration could potentially use the database to support its evaluation of investigational drugs and tests, and payors could use it to have a better sense of when patients are tested and if it's benefiting them.
So far no payors or regulatory bodies have publicly signed on with MED-C, although according to Dickson discussions with insurers are moving in a positive direction. After the N1N Registry gets going, MED-C plans to launch other projects that explore testing approaches in proteomics, immunology, and metabolomics. "The N1N protocol will be the first shot over the bow and we hope to quickly expand into other disease states," Dickson said.
A standardized, results-based NGS platform that is in a registry setting has never been done.
Standards for NGS
MED-C is trying to do a lot of things at once, Dickson admitted, but he would consider the program a success if the only thing that came out of it was a national framework for standardizing NGS tests. "We feel the most important thing is to build a registry that is looking at [genomic] alterations and collecting outcomes," Dickson said.
The NGS tests used to analyze patients' tumors for the registry will have to meet certain analytical requirements, which have been developed by a group of leading pathologist. According to Dickson, MED-C will internally vet these standards in the coming weeks. "Although it will come out as the MED-C testing standard, we hope it will be in line with where FDA, the College of American Pathologists, and Palmetto [the Medicare contractor in charge of MolDx] is going," he said.
He noted that MED-C had discussions with CAP and FDA in coming up with its NGS standards framework. FDA is particularly interested in what MED-C has come up with because "it's helping them with their LDT issue," Dickson said.
The FDA has issued a draft plan for regulating LDTs that the laboratory community has criticized as being incompatible with how labs operate. While the FDA is mulling its overarching regulatory strategy for LDTs, the agency has admitted that its current system is ill-suited for NGS, perhaps the most complex kind of LDTs. Since the agency is coming up with its own NGS standards (see related story), Dickson believes the FDA will welcome a prototype in this regard from MED-C.
By establishing NGS standards in NSCLC, MED-C is also creating a baseline for bringing future diagnostics tools to the market. "Now we have something we can compare liquid biopsies to, something we can compare protein signatures against," Dickson said.
Furthermore, in the community care setting, NGS standards would allow cancer patients in far flung parts of the country to have access to high-quality genomic analysis, and have a better chance at receiving personalized care. "A standardized, results-based NGS platform that is in a registry setting has never been done," Dickson said. "So, to have something like that allows us to take the next step toward a pan-companion diagnostic that everyone wants."
Currently, drugs are developed and approved alongside a companion test that gauges mutations in one or two genes. But this one drug/one test paradigm is becoming unsustainable as multiple precision drugs in the same class come to market, each with its own companion test. This can end up creating a lot of confusion for doctors who have to figure out which test goes with what drug when considering treatment options for their patients.
Universal companion diagnostics are one solution that industry players are working on. MED-C backers Illumina and Thermo Fisher have inked deals with pharmaceutical companies to develop such platforms, which could be used to detect multiple markers in patients' tumors and direct them to a range of treatment options.
The beauty of [registries] … is we can achieve some of the same goals that we could in a randomized clinical trial in a more rapid fashion, touching many more patients.
Getting payors on board
Ultimately, if payors join MED-C — depending on what they would commit to by signing on to the effort — it could bring much-needed reimbursement clarity for complex molecular tests. Most insurance plans consider NGS testing investigational, and labs like Foundation Medicine are tackling reimbursement case-by-case.
At a recent conference hosted by the Personalized Medicine Coalition and the Biotechnology Industry Organization, Foundation Medicine Medical Director Jeffrey Ross said in up to 70 percent of cases, healthcare providers have been asking insurers to give them a few months to track patients who have received treatment informed by NGS testing, so they have a chance to show benefit.
In advanced NSCLC, a number of payors — UnitedHealthcare, Aetna, and several Medicare contractors — have issued policies for NGS tests like Foundation's. However, as Dickson recently pointed out in The Cancer Letter, these policies all have different coverage criteria and may end up confusing healthcare providers.
Payors are also in a tough spot, Dickson told GenomeWeb. Insurers have been under pressure from industry and healthcare providers to cover NGS, but it has been challenging for them to evaluate and compare the different platforms. In the absence of this data, payors seem to be factoring in economies of scale with NGS panels, and pricing these tests based on what they would be paying for simpler LDTs analyzing genes such as ALK, EGFR, or ROS1, which have the most evidence in lung cancer.
"What is happening is fatigue is taking place," Dickson said. "Some payors are saying, 'Okay we recognize this is new technology. We recognize this as something that is important but we're going to treat it just like any other LDT and we're going to price it like you're replacing LDTs that would have normally taken place.'"
This has resulted in very low reimbursement for NGS panels, which labs say will restrict their ability to provide a high-quality testing service. "What people are not seeing is that quality will be sacrificed dramatically if they undercut what the cost of really doing a good service would be," Dickson said. "If someone says we're going to pay $600 for a NGS test, there is no good lab out there that can do something of quality for such low reimbursement."
At the BIO/PMC meeting, Michael Kolodziej, Aetna's national medical director of oncology solutions, raised some eyebrows by suggesting that the payment labs are receiving for NGS tests is likely more than their cost of goods to analyze a panel of markers. According to one industry leader, this demonstrates that payors don't understand the investment needed to develop complex diagnostics and provide an entire service, while diagnostics firms haven't done a good job of educating insurers.
Toward this end, Foundation recently launched the Precision Medicine Exchange Program, which like MED-C is trying to build evidence that shows payors more clearly the value of NGS testing and personalized treatment strategies. Within this consortium, medical centers, hospital systems, and community providers can share de-identified outcomes data on patients who have received molecularly informed treatments. And for when NGS testing suggests off-label treatments, Foundation will launch a pilot program with Genentech to provide consortium members access to drugs and connect patients to clinical trials.
Payors are certainly taking note of these precision medicine-focused collaborations. At the PMC/BIO meeting, Aetna's Kolodziej said he's had discussions with leaders at MED-C and with ASCO about a similar program called TAPUR. "The beauty of [registries] … is we can achieve some of the same goals that we could in a randomized clinical trial in a more rapid fashion, touching many more patients," he said. "It's going to be pretty clear when something is a winner."