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Abreos Biosciences Developing Assays to Monitor Patient Metabolism of Expensive Biologics


NEW YORK (360Dx) – Abreos Biosciences is developing a portfolio of assays that could be used, it said, to determine whether a patient is metabolizing the right dosage of biologic drugs targeting cancers, neurological disorders, and autoimmune diseases.

The San Diego-based firm does not have any assays on the market yet, but if it does get to the point of commercialization, it plans to make them available as laboratory-developed tests, with visions of bringing them to market as point-of-care tests, its CEO Bradley Messmer said.

Abreos' technology uses mimetope peptides that it calls Veritopes and that detect the concentration of a given biologic drug in a sample by mimicking the natural ligands of drug molecules. Further, they can be used in multiple diagnostic platforms, including sandwich ELISA and lateral flow assays for lab-based and point-of-care applications, Messmer said in an interview.

Veritopes are robust, cost-effective, and highly specific, and they would be made available for laboratories and eventually at the point of care to serve a largely unmet market need, the firm said.

"We're focused on improving the precision dosing of powerful, expensive drugs by enabling measurement of a drug in a patient so that they can adjust the levels accordingly," Messmer said.

At issue is that different people may metabolize the same amount of the same drug differently. As a result, some patients may not receive the optimal dosage of the drug.

Most people, Messmer said, are shocked when they see the variation in how people process drugs. "What is striking about it is that the variation is consistent across this class of expensive therapeutics. It really boggles your mind when you have drugs that are priced at thousands of dollars per dose, and people vary a hundredfold in the way that they process them, yet everyone is given the same dose," he said.

Daniel Cho, a medical oncologist at the NYU Langone Perlmutter Cancer Center, said in an interview that a large interpatient variation occurs in the metabolism of various oncology drugs and particularly small molecule inhibitors. Metabolism can vary due to the existence of polymorphisms in cytochrome P450 and ABC transporter genes, he said.

Further, he noted, drug levels achieved by the same dose can vary between individuals because of issues surrounding drug compliance and the presence of drug-drug interactions.

"Therapeutic drug monitoring, in theory, provides the potential for better individualization of therapy so as to maximize efficacy and minimize drug toxicity," Cho said. "Studies with many small molecule agents have shown that treatment response can correlate with a targeted drug exposure level."

Widespread use of therapeutic drug monitoring may not be necessary for all patients, he said, but it could be most useful in specific situations such as the potential for severe drug toxicity, the absence of an expected therapeutic response, and the presence of pre-existing organ dysfunction.

Taking precision doses of expensive treatments sometimes requires faster testing. Where receiving a rapid time to answer is critical, Abreos is developing point-of-care solutions for implementation in a clinic near the patient or eventually in the home as a "true point-of-care device" where a drop of blood could be applied, and the assay would operate similar to a digital pregnancy test and give an answer within minutes, Messmer said.

He noted that in oncology, quickly understanding treatment failure is "a big deal," while optimizing health economics is seen as vital in the monitoring of chronic diseases, such as multiple sclerosis and autoimmunity.

A point-of-care device is particularly useful for oncology patients who have been administered small-molecule chemotherapeutic agents, according to Omnica, which along with Purdue University is developing a PaperSpray Ambient Ionization system for use in the clinical laboratory and research applications to monitor therapeutic drug use.

Ultimately, Messmer noted, he hopes that some of the Abreos assays will be CLIA-waived and patients could potentially do testing at home, in the way that patients with diabetes currently do glucose monitoring. But the firm's strategic choice to first develop lab-developed tests has to do with achieving a faster time to market.

Messmer said. "Any point-of-care device would have to be [US Food and Drug Administration cleared] and that's at least a two-year process with associated expenses. However, one type of test does not preclude the other. We could start with a lab test and work toward having the point-of-care test approved."

He noted that patients would like to be able to use a point-of-care test to monitor doses of drugs that can cost $5,000 per treatment. Point-of-care testing is important, he said, because of a trend towards patients doing self-medication. "If they can avoid it, they don't want to have to come into a clinic for an intravenous infusion," he said.

NYU's Cho noted that although anticancer drugs are not currently self-administered, "there has been a substantial move … [toward] the development of oral anticancer therapies particularly small molecules." Therapeutic drug monitoring is expected to be useful, he said, "in the setting of self-medication given the potential issues of drug-drug interactions and differing patient compliance."

More precise monitoring of the presence and concentration of a drug in the body is generally being driven by patient health and health economic concerns, Messmer said.

"There are pretty good data which show us that 20 to 30 percent of patients with low drug levels in their bodies don't get a full, or in some cases, any therapeutic benefit," Messmer said.

In some cases, you could try to give them more of the drug and try to get them into a therapeutic window, but in other cases you'll never be able to give them enough, he said. In these circumstances, time and money is wasted on a therapeutic that won't work, and it can be devastating for a patient's health outcome, he said. It's an especially important concern when other drugs are available that the patient could switch to and that could be more effective.

He noted as an example Rituximab, which is used to treat non-Hodgkin's lymphoma or chronic lymphocytic leukemia. Eighty percent of patients respond to the treatment, but doctors don't know why it doesn't work for the rest of the patients.

"They have other therapeutic options, so it is really important for them to understand if it is the drug is at a very low level in the patient. Conversely, if a high level of the drug is in the patient's body and it's not working, that tells you that it's the wrong type of drug and you should go to a different therapeutic strategy."

Abreos' tests are currently not commercially available, but during the next few months, it expects to launch a lab-developed test for use with Tysabri (natalizumab), a drug co-marketed by Biogen and Élan. It's a humanized monoclonal antibody against the cell adhesion molecule α4-integrin used in the treatment of multiple sclerosis and Crohn's disease. The treatment increases the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability.

"Its dose is not adjusted right now," Messmer said. "Everyone gets the same 300 milligrams every four weeks, and there's a strong feeling that is about to be supported by data that many patients get too much, and that increases the risk of the black box warning side-effect PML."

He noted that neurologists working with Abreos who "have been at the forefront of this area" are extending the time between doses for patients to five or six weeks from four. "But they are doing that based on their clinical intuition and without having data that could help them know which patient should be dose-extended and which shouldn't," he said.

Abreos was founded in 2013 based on technology developed in Messmer's lab at the University of California, San Diego, and later licensed to the firm. The company currently is developing tests for eight out of the top 12 drugs used to treat neurology, oncology, and autoimmune conditions. Messmer said he expects that the company would have assays to test for concentrations of all the top drugs in these applications "in the next few months."

For use of the assay with Tysabri, Abreos has completed a deal with a CLIA-certified lab, which he declined to identify. The firm expects to launch a panel of assays for oncology applications before the end of this year, and for autoimmune conditions at the beginning of 2019.

Although there are no FDA-cleared drug monitoring tests, a few companies are focused on providing diagnostic tests that detect the level of anti-tumor necrosis factor (anti-TNF) treatments used in gastroenterology, Messmer said.

San Diego, California-based Prometheus Laboratories, for example, has a portfolio of therapeutic drug monitoring tests that includes tests for Remicade (infliximab) and its biosimilars, and Humira (adalimumab), among others. In October 2016, the firm introduced a new therapeutic drug monitoring test for use in adult inflammatory bowel disease patients treated with Janssen Biotech's Stelara (ustekinumab).

Other companies providing tests for therapeutic drug monitoring include Quest Diagnostics, Laboratory Corporation of America, Inform Diagnostics, and Grifols. In June 2017, Grifols said that it was expanding its Texas-based Clinical Diagnostics Laboratory menu by launching therapeutic drug monitoring testing services.

Messmer noted that therapeutic drug monitoring tests on the market can cost between $250 and $2,500 per test and, in some cases, patients are already paying $5,000 in addition to other expenses for each treatment.

Abreos' tests are inexpensive to produce and give the firm pricing flexibility; it could be possible to produce its point-of-care tests for a few dollars at scale, Messmer said.

The firm is evaluating how much to charge for its tests, Messmer said, and needs to investigate the value of providing a test that has "the ability to save thousands of dollars in drug costs." The firm expects to provide its tests as a subscription service rather than on a fee-per-test basis.

He noted that achieving reimbursement from payors is also a priority. To obtain reimbursement for patients, the firm would need to provide examples of where its tests have shown that they have improved clinical outcomes or cost savings, he said. As a result, the firm will probably provide its first test for Tysabri for free for some time, so that the company can "begin to collect clinical data, drive adoption, and get some initial market penetration," he said.

Abreos has raised $3.5 million from angel investors and received $5 million in NIH grants. The firm is gearing up for a Series A round through which it hopes to raise between $5 million and $10 million, Messmer said.

The firm would use the funds to conduct clinical studies and build out contracts with pharma and payors, it said.

According to the firm, the total market for therapeutic dose monitoring is valued at around $3 billion in a drug market valued at about $287 billion.

The case for providing more precise dosing is quite clear-cut from patient health and health economics perspectives, Messmer said. "When we speak of precision medicine, this is really the low hanging fruit. We should be giving the right amount of a drug to a person when it is as easy as just measuring the amount of that drug in their blood. And when your therapeutic costs as much as a Ferrari, it should come with a speedometer."