When Amgen’s Imlygic became the first FDA-approved cancer-killing virus on the market in 2015, oncologists and Wall Street analysts alike predicted the product would ultimately work better in combination treatments than it does on its own. At closely watched annual conference of the American Society of Clinical Oncology (ASCO) in Chicago, starting today, scientists will present data from several combo trials involving the drug, which is an engineered form of the herpes virus. The results that should provide some hints about the potential value to patients of combining different immune-boosting approaches to treating cancer.
But the data is coming amid a broader debate about the value to society of high-priced cancer treatments. In fact, during the ASCO event, one group of researchers will publish a study suggesting that combining Imlygic with Bristol-Myers Squibb’s immuno-oncology blockbuster Yervoy in melanoma patients may not be cost effective, given results from early trials showing that the combo isn’t that much more effective than Yervoy alone at extending life. Questions about cost effectiveness will only grow more intense as President Donald Trump’s administration continues its war-on-words on drug pricing.
First, a look at the science of virus-based treatments, also called "oncolytic" viruses, is in order. The scientific community has long been aware that several viruses have an innate ability to kill cancer. Recent advances in genetic engineering techniques have resulted in inventions like Imlygic, which was designed to destroy tumor cells directly while simultaneously prompting the immune system to find metastatic cells and kill them.
During ASCO, data from studies of Imlygic combined with other therapies will be presented. Several trials combining Imlygic with "checkpoint inhibitors," such as Yervoy, which work by blocking proteins that normally prevent the immune system from recognizing and destroying cancer, are underway in a variety of cancer types, including head and neck cancer, liver cancer and sarcoma.
And other companies are working on engineered versions of viruses like polio and vaccinia (a close relative of cowpox), many of which are being tested in combinations that will be discussed during ASCO. For example, scientists working with France-based Transgene are presenting data on Pexa-Vec, an engineered form of vaccinia, that they say supports a strategy of administering the drug prior to giving a checkpoint inhibitor to treat patients with metastatic melanoma or colorectal cancer. And researchers working on an engineered form of the herpes virus from Japan-based Takara Bio are presenting data from a phase 2 trial in advanced melanoma that they say shows a positive benefit/risk profile of combining the drug with Yervoy.
But should the additional cost of prescribing two immune-boosting treatments instead of one also be considered a risk? Yes, says a team at the University of Arizona Cancer Center. Their study, which will be published in ASCO’s Journal of Clinical Oncology, concluded that every 1% increase in positive responses from combining Imlygic with Bristol-Myers Squibb's blockbuster checkpoint inhibitor, Yervoy, would cost $1,731,558. For most U.S. insurers, that may not be cost effective compared to Yervoy alone, they argue.
They reached that conclusion based on data presented last year. The study, involving 198 patients, met its primary endpoint, producing a response rate for the combo of 38.8%, vs. 18% for Yervoy alone, according to the abstract. But despite that despite the significant difference in response rates in patients taking the combo treatment, the clinical trials have so far not shown an improvement in progression-free survival—the amount of time patients lived without their cancer getting worse—according to the Arizona researchers.
A spokesperson for Amgen said in an email that the cost-effectiveness study is “premature” because survival data from studies of immuno-oncology combination treatments will require longer follow-up periods. “Therefore, this analysis is not a fair reflection of the value and the full potential of oncolytic virus-based combination therapies,” she said. Amgen continues to follow the patients in the study that the Arizona researchers used to calculate cost effectiveness, she added.
Meanwhile, the affordability of new cancer treatments continues to drum up debate in the cancer community. A quick search of presentations planned at this year’s ASCO turns up more than 300 studies, proposals and discussions addressing the high cost of cancer care and strategies for helping patients cope with their bills.
The cost discussion won’t be ending anytime soon. A new report from the trade group Pharmaceutical Research and Manufacturers of America (PhRMA) finds more than 1,100 cancer treatments under development, including 260 immuno-oncology products. The group charts more than 20 clinical trials involving oncolytic viruses.
