Originally published July 8.
NEW YORK (GenomeWeb) – Personalized medicine firm Genomas and diagnostic developer AutoGenomics are planning to develop and launch a multiplex genetic test that doctors can use to assess whether patients will respond well to statins or whether they are at risk of experiencing muscle pain and injury.
Under the terms of the agreement announced earlier this week, the partners will combine Genomas' SINM PhyzioType System with AutoGenomics' Infiniti multiplexing genetic test platform to advance a test that can identify patients with heart disease and diabetes who are likely to experience myalgia (muscle pain) and myopathy (muscle injury) with certain kinds of statin drugs. "AutoGenomics provides the physical entity, which is the chip," Gualberto Ruano, Genomas president and director of genetics research at Hartford Hospital, told PGx Reporter. "Genomas provides the algorithms that turn that chip into clinically useful information for the physician."
Genomas has for many years been researching the genes associated with statin-induced adverse events in patients with lipid disorders and fine tuning a proprietary physiogenomic method for predicting patients' outcomes to treatments. "Physiogenomics," as described in the patent awarded to inventors Ruano and Andreas Windermuth, integrates individuals' genotypes, phenotypes, and a population analysis of functional variability, and establishes a method for predicting treatment response.
In its work developing the test, Genomas has been successful in garnering several small business innovation research grants from the National Institute of General Medical Sciences over the past five years. "We have been through the entire cycle of SBIR grants with NIGMS," Ruano said. He noted that the funding has supported Genomas' ability to genotype close to 2,000 patients and develop the PhyzioType algorithm for statin response in collaboration with Hartford Hospital.
Drawing data from genotyped patients, "we feed the algorithms [data on] who develops a myopathy and who does not, who has a very positive response to the statins and who does not," Ruano explained. "That kind of clinical diagnostic information has been factored into the analysis."
For example, in one study published in 2011 in Atherosclerosis, Ruano and colleagues genotyped 793 patients treated with statins – approximately half had myalgia and half did not – in an effort to identify adverse event-linked markers from a set of 31 candidate genes. Through this analysis, the researchers validated that COQ2, ATP2B1, and DMPK were associated with statin-induced myalgia. "The three genes integrated into a physiogenomic predictive system could be relevant to myalgia diagnosis and prognosis in clinical therapy," the investigators concluded.
Similarly, Genomas has published on several other genes associated with statin-induced myalgia and myopathy, and will refine the gene panel gauged by the test it is developing with AutoGenomics. "Genomas has performed considerable research and identified specific markers of interest," Ram Vairavan, AutoGenomics senior VP, told PGx Reporter. "In developing our test panel, AutoGenomics will include the specific markers developed by Genomas ,as well as key markers that have published in the literature to determine risk associated with statin-induced myopathy."
Statins are among the most commonly prescribed medications worldwide for helping patients lower their levels of low-density lipoprotein (LDL) cholesterol. The US Centers for Disease Control and Prevention estimates more than 71 million adult Americans currently have high LDL, while 43 million are prescribed statins to keep their LDL levels in check.
Although studies have shown that statin use is associated with a 30 percent reduction in cardiovascular risk in different populations, some patients treated with statins experience myalgia, which can progress to more serious myopathy. In clinical trials, these statin related adverse events have shown up rarely in between 1.5 percent and 3 percent of patients. Meanwhile, the adverse events rates are much higher in observational trials, affecting between 10 percent and 15 percent of patients.
The latest guidelines from the American Heart Association and the American College of Cardiology recommend statin therapy more broadly, and as such, Ruano believes that more people may experience myalgia and myopathy. Issued last November, the latest guidelines call for moderate- or high-intensity statin treatment for those who have cardiovascular disease; people with LDL levels of 190 mg/dL or higher; patients between 40 and 75 years of age with type 2 diabetes or a high 10-year risk of cardiovascular disease.
"The issue of statin-induced myopathy is clinically very complex," Ruano reflected, noting that by and large statins are good drugs. "However, as more people are using these statins … there will be more exposure. The minute you get [statins] into larger and larger populations, now you're going to start seeing the lack of efficacy and the side effects more.
"In the context of moving statins to a larger population," a genetic test that can predict who will respond well to these drugs and who won't, "is the right safeguard to have," Ruano said.
According to Vairavan, AutoGenomics will begin pre-marketing efforts around the test later this year. The companies will complete implementation studies ahead of full commercialization of the test. "We will be launching a series of studies on the chip and validating its predictive accuracy both with regard to the statin myopathy … as well as [with regard to] the efficacy," Ruano said.
The latest agreement between the two firms extends an ongoing relationship. Genomas has previously used AutoGenomics' platform in its clinical lab. The efforts to launch a statin response test will be backed by AutoGenomics and Genomas. "We are also in the process of contacting pharmaceutical companies that are developing statin alternatives" that could be potential partners, Vairavan noted.
Ultimately, adoption of the test will depend on reimbursement and AutoGenomics will handle discussions with payors. "[We] would like to take advantage of the new regulations with [the Centers for Medicare & Medicaid Services], wherein a provision in the law creates a special category for advanced diagnostic tests," Vairavan said.
The newly passed "Protecting Access to Medicare Act of 2014" stipulates that as of 2017, CMS will pay labs based on a market-based system – according to the weighted median of rates from private payors for tests. Labs will have to begin reporting rates from payors to CMS in 2016. Although the market-based pricing provisions apply to all clinical labs, HR 4302 sets up a new category of advanced diagnostic laboratory tests – defined as a test that gauges multiple markers based on an algorithm or a test approved or cleared by the FDA. An advanced diagnostic must be a single-source test; that is, it has to be sold by the lab that developed it.
According to the new law, CMS will update pricing annually for advanced tests. For all other diagnostics, pricing will be updated every three years.