REUTERS: In the halls of MD Anderson Cancer Center, the drug Vitrakvi is known for having a "Lazarus effect" in some patients because it can reverse late-stage cancer that has defied all other treatment options.
Developed by Eli Lilly and Co's Loxo Oncology and marketed by German drugmaker Bayer , it fights a rare genetic mutation that appears in less than 1per cent of solid tumors, regardless of where they appear in the body.
Finding those patients will require widespread adoption of sophisticated tests that look for multiple genetic alterations that could be driving the cancer.
So far, progress has been slow.
Adoption of so-called next-generation sequencing (NGS) tests has been stalled by lack of reimbursement from insurers over concerns that the evidence is not there yet to support widescale use, according to more than a dozen interviews with oncologists and pharmaceutical and diagnostic industry executives.
As a result, pharma companies from small biotech Blueprint Medicines Corp to larger rivals Lilly and Roche Holding AG are taking matters into their own hands, bulking up staff to increase patient and physician awareness about testing and building up a gene testing infrastructure that for many community hospitals still does not exist.
Bayer executives told Reuters it plans to spend US$70 million to increase patient and physician awareness of testing for rare mutations and to encourage regulatory approval of more tests. They expect that budget to expand as Vitrakvi continues to win approval in other countries.
Lilly told Reuters the company has signed an agreement with Thermo Fisher Scientific to develop a companion diagnostic test for its experimental drug, LOXO-292.
The deal adds RET mutations - the target of both Lilly's and Blueprint's drugs - to Thermo's Oncomine Dx Target Test, which local pathology labs can use to identify multiple genes linked with non-small cell lung cancer.
The agreement is aimed to help identify more lung and thyroid cancer patients who may benefit from the Lilly or Blueprint therapies. The Thermo test is already approved by the U.S. Food and Drug Administration - a key standard for Medicare coverage, the companies said.
According to Dr. Brian Alexander, chief medical officer of Roche's gene testing company Foundation Medicine, only about 15per cent of U.S. patients with advanced cancers get comprehensive genomic profiling. Another 25per cent get single-gene testing, he said, and a large proportion "are not getting any testing at all."
At MD Anderson, which sees 100,000 new cancer patients a year, only around 10,000 eventually have their tumors sequenced.
For a rare few, the tests are lifesaving.
Xin Zheng, 47, a mother of three in Michigan who was referred to Reuters by Blueprint, was diagnosed with stage 4 lung cancer in 2016. After failing several treatments, she was out of options.
Her husband, Zhigang Wei, asked for genetic sequencing, and the test turned up a RET mutation. After contacting multiple lung cancer experts, Zhigang found an early-stage clinical trial treating patients with Blueprint's experimental drug, BLU-677.
Now, Xin is nearly back to normal.
“My wife is lucky," he said, adding her quality of life is much better and she has hope for the future.
Finding patients with such rare mutations is like "looking for the needle in the haystack," said Stefan Oelrich, head of pharmaceuticals at Bayer.
Dr. David Hyman of Memorial Sloan Kettering Cancer Center, who tested Vitrakvi in clinical trials, said making these tests the norm for advanced cancer patients will require a huge shift in the way oncology is practiced.
"It's painful to know there are patients out there with these alterations who are dying without knowing about it and without getting any treatments," he said.
NOT GETTING TESTED
For Bayer's Vitrakvi and Roche's Rozlytrek, along with similar drugs in development, genomic testing is critical to finding patients who can benefit from them.
Cancer patients and drug companies alike got a boost last year when the federal Medicare health program for the elderly and disabled said it would cover FDA-approved tests for advanced cancer patients that can identify hundreds of genetic mutations at once. A Medicare endorsement is generally followed by widespread coverage decisions by private insurers.
But the final regulations dropped a requirement that testmakers prove the tests are cost-effective and improve patient care. That created an "evidence gap" that has allowed some insurers, also known as third-party payers, to withhold coverage or demand more proof that they benefit patients, said Jeff Schreier of Diaceutics PLC , a data analytics company that works with drugmakers to improve diagnostic testing.
"More payers are coming around, but it's slow," he said.
The most recent coverage policy from CVS Health Corp's Aetna approves many single-gene tests for specific cancers, but still largely considers multi-gene tests experimental. Anthem Inc's policy limits testing to "medically necessary" use and states there's "insufficient published evidence" to support widespread testing.
And while Foundation Medicine's and Thermo Fisher's tests are getting reimbursed from Medicare, many hospitals such as MD Anderson, which have developed their own tests, are not guaranteed payment. "Reimbursement is still a driving force," MD Anderson's Kenna Shaw said of genomic testing, which costs an average of US$5,000 per patient globally.
Lilly bought Loxo in January for US$8 billion to profit from its targeted drugs in early-stage development. Bayer secured the rights to Loxo's two leading compounds in a 2017 alliance.
Dr. Anthony Sireci, Loxo's senior medical director, said the company has been working to "democratize" testing in the United States by increasing its use in local pathology labs, where most cancer testing has traditionally been done. The Thermo Fisher agreement will support those goals and expand patients' access to "high-quality genomic testing," he said.
"TEST YOUR CANCER"
Bayer has hired diagnostic experts to help its medical and sales staff assess the barriers to genomic testing and ensure that local pathology labs are including the genetic alterations targeted by its drugs when they profile tumors, the company's oncology strategic business chief Robert LaCaze said in an interview.
Bayer also launched a public awareness campaign called "Test Your Cancer" that urges patients to ask their doctors about genomic cancer testing. The company is working with testing providers to ensure test reports are easy to understand.
Blueprint, which has six genomically-targeted drugs in development, told Reuters it plans to hire six diagnostics experts to increase awareness of the mutations their drugs target, especially in community medical practices, where 70per cent of cancers are treated.
Bayer sees signs of progress. Based on internal data, the company estimates average sequencing rates across tumors neared 30per cent last year, and the company saw a two-fold increase in the number of labs offering tests that carry the mutation targeted by Vitrakvi.
Bayer has not released sales figures for Vitrakvi.
Asked for an update in the most recent earnings call in July, Bayer's Oelrich said uptake is going "according to plan," but declined to say how many patients are using the drug. LaCaze said with very rare cancers like the ones Vitrakvi targets, sales growth is "something that will build over time."
(Editing by Michele Gershberg and Edward Tobin)