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Foundation Medicine to Double Testing Capacity, Show Efficacy of Test in Clinical Trials

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Following the launch of its sequencing-based cancer profiling test last month, Foundation Medicine is planning to double its testing capacity and is conducting clinical trials to prove the impact of its test on doctors' treatment decisions and patient outcomes.

Earlier this month at the American Society of Clinical Oncology Annual Meeting in Chicago, the company presented results for the first 304 commercial samples tested in its CLIA lab, showing that the test could find actionable alterations in around 80 percent of samples. Notably, about 60 percent of samples had actionable mutations that would not have been detected by any of three commonly used "hotspot" mutation panels.

The privately held company, which is in the midst of a Series B financing, is also expanding its collaborations with pharmaceutical companies: under a new agreement with Novartis made public last week, it will conduct genomic profiling on most patients enrolled in Novartis' phase 1 and phase 2 oncology clinical programs over the next three years.

Foundation Medicine commercially launched its cancer genomic profile, called FoundationOne, late last month, following a "soft launch" over the last half year or so.

The test, which has a list price of $5,800, is available worldwide for all solid tumor types. It uses routine formalin-fixed paraffin-embedded samples, requiring about 50 nanograms of DNA.

Currently performed on the Illumina HiSeq platform in the company's Cambridge, Mass.-based CLIA lab, the test sequences 3,230 exons of 182 genes known to be mutated in solid tumors, as well as 37 introns from 14 genes known to be rearranged in these cancers, to a depth of more than 500x.

It detects all classes of genomic alterations, including substitutions, insertions and deletions, copy number alterations, rearrangements, and splice variants.

The test classifies genomic alterations as 'actionable' if they have been linked to an FDA-approved therapy in any solid tumor; if there is a known or suspected contraindication to a therapy; or if a clinical trial has been linked to the alteration.

The current turnaround time is around 21 days, but a high-priority goal is to decrease this to 14 days, said Vincent Miller, Foundation Medicine's senior vice president of clinical development.

So far, the company has analyzed about 400 commercial clinical samples, from across the US as well as other countries, Miller told Clinical Sequencing News, and receives between 40 and 60 samples per week.

It currently has sufficient capacity to run about 250 samples per week, which it plans to double to 500 or more "in the not-too-distant future," he said.

While Foundation Medicine remains "platform-agnostic" regarding the sequencing technology it uses, "we think [the Illumina HiSeq] is the best platform on which to perform this genomic analysis presently," he said.

Pricing for the test is expected to remain stable, at least in the short term. "We certainly are aware of the fact that sequencing per se is dropping in price, but that is a relatively modest component of the overall pricing of the test," Miller said.

Foundation Medicine has been billing patients' insurance companies for the test and has been "pleasantly surprised to date with our reimbursement on a number of cases in which we have had the full process run through," he said. So far, the company has received payment for more than 20 cases and is awaiting payment decisions on several others.

Clinical trials will be essential for the company's general reimbursement strategy, and it is conducting or planning several such trials, some developed in collaboration with its clinical partners.

In one trial, a so-called decision impact study, it is tracking doctors who were planning a certain treatment before the test but changed their decision after getting the test results. An analysis of the percentage of physicians who changed treatment strategy — also called the switch rate — is expected within the next six to nine months, Miller said.

Other studies will look at patient outcome, or efficacy endpoints, such as whether patients' cancers shrink more, their cancer-related symptoms improve more, and whether they live longer under a changed treatment compared to conventional therapy. While such measurements are more common in therapeutic rather than in diagnostic trials, the company still believes its test warrants these types of studies, and has efficacy endpoints included in ongoing or planned clinical trials, Miller said.

In addition, Foundation Medicine plans to generate case reports, for example of cases where a genomic alteration was detected unexpectedly in a certain cancer and was linked to a treatment. According to Miller, these cases "will also be critical in resonating with payors."

Finally, the company is betting that endorsements of the test by "key opinion leaders" with no financial ties to Foundation Medicine will be "a strong factor" in persuading some insurance companies to reimburse the test.

At ASCO, the company presented results from the first 304 commercial samples analyzed in its CLIA lab between October 2011 and April 2012. Those are separate from the samples it has sequenced as part of collaborations with academic medical centers and pharmaceutical companies.

Samples included a variety of solid tumor types, about half of them lung, breast, or colorectal cancers. In addition, ovarian, pancreatic, bladder, head and neck, and gastric cancer were represented. About a quarter of all samples came from a variety of less common cancer types.

In total, the test found 450 unique genomic alterations, including 193 actionable ones in a total of 54 genes. Perhaps not surprisingly, the most commonly mutated genes were TP53, KRAS, PIK3CA, APC, EGFR, CDKN2A, and MYC.

In 77 percent of samples, or 224, the test yielded at least one actionable alteration. On average, each sample had 1.36 actionable changes, ranging between zero and four. Overall, each sample had 2.66 genomic alterations on average, ranging between zero and seven.

For the three most common solid tumors alone — lung, breast, and colorectal cancer — the test discovered actionable alterations in an even greater fraction, between 85 percent and 90 percent of samples.

Of note, 59 percent of samples, or 172, had at least one actionable mutation that would not have been detected by three commonly used "hotspot" tests — the SNaPshot, OncoCarta, and OncoMap panels.

Also, only 37 percent of all alterations detected by the test would have been found by the three hotspot tests or by single gene tests for HER2 and EML4-ALK.

Overall, the test was successful in 96 percent of samples, failing in 12 samples.

Miller noted that the test could be especially useful for uncommon tumor types, which made up about 25 percent of all samples in this study. In many cases, there is no effective therapy approved for these cancers, and often they are not well characterized genomically because more common tumor types are prioritized in research studies. "We think this is a particularly useful indication for FoundationOne and have seen some really exciting results on samples [from unusual tumors] that were studied," he said.

While the current test, which is solely based on DNA sequencing, was the most straightforward way to get to genomic alterations that can be linked to therapies, future incarnations of the test will likely include other measurements, such as RNA expression, epigenetics, or phosphoproteomics. The company also plans to cover other cancer types beside solid tumors, such as leukemias and lymphomas.

Another diagnostic test Foundation Medicine may develop in the future is a recurrence test that monitors genomic alterations in the patient's blood, he said.

Besides its commercial test and academic collaborations, the company is expanding its pharmaceutical partnerships. Following a pilot project with Novartis that started 18 months ago, Foundation said last week that it has extended the collaboration for another three years. During that time, Novartis plans to use Foundation's genomic profiling test across many of its phase 1 and 2 oncology clinical programs, conducting it on most patients enrolled in these trials.

The new agreement is "an endorsement of the value of our test in informing the interpretation of either completed trials or the design of future trials," Miller said.

"Novartis has a similar view as to how we are going to help cancer patients going forward — looking at specific genomic alterations in specific patients; looking at combinations of therapy that are rationally developed based on those molecular alterations, not monotherapy; treating all patients with a given morphologic type of cancer similarly," he said.

Foundation Medicine, which also has partnerships with Sanofi, Johnson & Johnson, Celgene, and Array BioPharma, is currently talking with a number of other large pharmaceutical and biotech companies and hopes to pen additional collaborations before year's end, Miller said.

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