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Elaine Quilici is Pharmaceutical Executive's Senior Editor. Email her at firstname.lastname@example.org
How current barriers along the roadway between biomarker testing and drug prescribing can affect decision-making for precision medicines.
How current barriers can affect prescriptions in precision medicine
The value of precision medicine, which relies on identifying biomarkers to treat particular conditions, is clear. And its prevalence to treat disease-especially cancer-is only expected to grow. According to an October 2019 report by The Insight Partners, the global cancer biomarkers market could reach $31.2 million in 2027.
Yet despite such a strong current, the biopharmaceutical industry faces a number of barriers along the pathway between biomarker testing and drug prescribing. These include how physicians order diagnostics, how samples are transported to the lab, how results are returned to healthcare professionals (HCPs), how doctors interpret reports, and regulatory and reimbursement issues surrounding the entire process.
In these areas, something seems to be getting lost in the flow between laboratory professionals and physicians, and pharma would benefit from stepping in to offer support before the issues grow exponentially along with the field.
Many precision drugs require tests called companion diagnostics. These differ from complementary diagnostics, which may not be required per the label but may be ordered by physicians at their discretion to use in therapeutic decision-making.
When developing a drug that requires a companion diagnostic, development of the diagnostic should ideally be run in parallel, and the drug and test should be available at the same time. However, as many precision drugs are fast-tracked by regulators, these medicines are leaving diagnostics in their trail. When a test does not progress at the same pace, FDA has been approving the drug with post-marketing commitment, so as to not limit access to a life-changing drug.
“I think we have to look at those situations and understand what is the risk-benefit of putting the drug out there and having it available to these patients,” says Jordan Clark, chief technical officer, Diaceutics, a diagnostics data analytics and implementation services provider for global pharmaceutical companies. “[Bayer cancer drug]Vitrakvi has a 91% response rate in pediatric cases. That’s a wonder drug. And delaying that by a year or two just because the test isn’t available, in my view, it’s probably not ethically right.”
To ensure there was a diagnostic available for Vitrakvi, Loxo Oncology and Bayer supported using laboratory-developed tests (LDTs) and worked with big institutes and independent labs to make sure testing was available without an approved companion diagnostic.
According to Diaceutics, almost 75% of oncology testing in the US is provided using such LDTs. These tests take the place of commercially developed, FDA-approved tests and, says Clark, are “perfectly fine” in the US under the Clinical Laboratory Improvement Amendments (CLIA) regulation framework.
But physicians often don’t realize substitutions are being made. When ordering a test where there is no approved diagnostic, it is the lab that generally decides which LDT to use. And a lack of education often leads clinicians to leave choices up to the labs.
“What we find is the physicians just order a biomarker-so they’ll say, I want an EGFR test, or I want a PD-L1 test-they don’t specify a methodology or an FDA-approved test,” says Clark. “This can be confusing for physicians, particularly if you look at a Quest, LabCorp, or NeoGenomics test menu. They may have two or three different tests that cover the same biomarker. Physicians are not aware of the differences, and the advantages and the disadvantages between those. In many cases, the lab is not giving that information for them to make an informed decision. I wouldn’t purely put it at the physician’s feet; labs could be better there as well.”
Without a requirement for FDA clearance, labs are free to develop their own tests, either alone or in partnership with pharma, which is creating market competition. “Now you’re a physician hearing from 10 different laboratories as to why you should use their assay over others,” says Jeff Ellis, co-founder and managing director of Crosstree Capital Partners. “I can’t imagine how challenging it is for physicians to keep up with the latest and greatest, because there’s constantly three new things coming out, which are the latest and greatest, arguably, so it’s a challenging landscape for physicians.”
To address this confusion, pharma companies could reach out to physicians to keep them informed of current research that might prove insightful. They could also improve engagement through providing online diagnostic tools to assist in HCP decision-making.
But it goes beyond educating the physician. As new biomarkers come to light, the importance of multidisciplinary teams should play a bigger role.
“It’s fairly hard for one treating physician to keep up to date with all of the latest advances,” says Clark. “We really should be thinking about this as a team effort and having particular specialties [such as the oncologist, radiographer, and pathologist] involved in order to ensure those patients are tested in the most appropriate manner. There’s a really key role there for pathologists to educate.”
Logistics can be another hurdle. Many of these specialized tests aren’t available locally, meaning samples oftentimes need to be transported. “As we look at some of our newer tests in precision medicine, particularly around liquid biopsy testing and gene therapy testing, those logistics can become more complicated,” says Clark. “We may have to get samples to a lab within four hours, or we may have to use specific tubes, or we may have to use ultra-cold temperature (dry ice) logistics. Those things make it more complicated than perhaps a routine tissue sample and EGFR-type of mutation testing.”
Turnaround time of lab results is another area that could be improved. A delay in reading results could prolong a physician’s treatment decisions.
“One of the biggest areas of patient leakage is the interpretation of the results and making sure that result is given to the physician at the right time,” says Clark. “Here, the clarity of reporting is very important-actionable reports that allow physicians to understand and interpret the result into a clinical and/or therapeutic decision. Making sure that they’re getting that at the right time is key.”
For example, Clark points out that most acute myeloid leukemia patients will be treated within three days of their diagnosis. Glioblastoma patients however, who just had open brain surgery to remove a tumor, don’t need those biomarker test results for multiple weeks, until they recover before going on any systemic therapy. “So understanding the disease and the urgency is really important as well,” he says.
Much of the sample input and data output falls on the laboratory, but there can be other gaps that cause problems, such as basic technology.
“An important KPI for laboratories is the time between when the sample or order comes in-receiving-and when they report the result out-lab turnaround time,” says Clark. “But there is time on either side of that, that is not within the laboratory’s control, which is not measured very well. [For example,] in Europe, we actually see that
fax machines are still being used for reporting, and that adds a day or two to when that result is available to when the physician actually sees it in front of them. If you don’t use a well-integrated [electronic medical record] system, then sometimes there can be delays in that reporting aspect of it.”
Pharma should look to the laboratory as a valued communication conduit to physicians. “You can educate the laboratory around tests and around eligibility for therapy, which then can be used as an information channel from that laboratory to physicians,” says Clark. “We often talk about the physician-lab interface as an untapped communication channel, whereas if we educate the laboratory, they can disseminate that information at the right time when a physician is needing to make treatment decisions.”
Pharma also could benefit from investing in education and training of physicians when it comes to understanding lab reports. Explaining how to interpret genetic information and then how to communicate its meaning to patients along with any treatment implications could improve the process.
Though oftentimes genetic counselors are used for this role, the better informed HCPs are, the better they can work with patients to make life-changing decisions.
“Last year, [a study by] Flatiron and Foundation Medicine said even when patients received the right test and they had the report in front of them, the physician still didn’t put them on a targeted therapy,” says Clark. “That was in lung cancer, and it ranged from around 60% to 70% in EGFR/ALK, but down at 33% for NCCN [National Comprehensive Cancer Network] biomarkers and therapies with lower prevalence. So even if you get everything right in that testing journey, your physician may still not give you a targeted therapy even though the guidelines support that. I think that talks a lot to the education needs of those oncologists.”
Ellis believes that one of FDA’s biggest challenges is trying to regulate the diagnostics market. “It’s a huge task for the FDA,” he says. “I think we’ll continue to see more progress toward definition for reasonable ways for diagnostic tests to get approval and benefit patients in the end, but I think we still have a good ways to go before
there’s a structure in place that everyone feels comfortable with.”
Ellis does think regulators have made significant strides in trying to adapt to the changing landscape. “Look at Foundation Medicine-owned by Roche-and their comprehensive genomic panel diagnostic test,” he says. “They worked with the FDA to expedite. The FDA set up a program wherein a company like that, if they make the requisite investment and develop a diagnostic test, they can have a pretty unique market position in the end. So the FDA are taking the right steps, but the landscape is changing so fast, and patient needs and innovation are advancing so quickly that it is hard for the FDA to keep up.”
Issues around treatment reimbursement also exist. For example, some healthcare insurance plans may require a patient to undergo conventional chemotherapy before they can access a targeted therapy, even though the guidelines state that those patients should go on targeted therapies beforehand.
“Sometimes, it’s not just the physician, but it’s the reimbursement systems around them and their practice within their institute or their managed care, where they have local guidelines to reduce costs, which actually might be inhibiting precision medicine,” says Clark.
A recent study by Diaceutics uncovered a loss of 77,856 patients per year to therapy and a revenue loss of $8.3 million per year to pharma in the US. These losses amounted to an estimated 30% of the oncology patient market and more than $16 billion per year in the US alone.
“Some pharmaceutical companies [still] have not fully embraced diagnostics,” contends Clark. “They still think of it as a barrier, which they really shouldn’t do, because it’s that important for the success of their drug. Diaceutics
has shown that every dollar spent in your diagnostics strategy has a return of investment of around 30 times. It really is that gatekeeper to those patients, and it is as simple as if you have a targeted therapy and don’t get the test, you don’t get the therapy.”
As precision medicine continues to explode, Ellis echoes the importance of further cohesion and alignment between pharma and diagnostics and medical laboratories. “The more lockstep pharma and diagnostics are there, the clearer the message will be to physicians in their decision-making and the hope it will benefit patients in the end,” he says.
Elaine Quilici is Pharm Exec’s Senior Editor. She can be reached at email@example.com