When a patient picks up medication at the drugstore, it usually comes with a list of likely and unlikely side effects – including a warning to contact a doctor in the event certain of those surface. And determining these reactions is one of the things that slows a drug's path to market and greatly increases its R&D costs.
Question: How can you do this earlier – even before human testing – to speed the commercialization or determine that the risks of development aren't worth the ultimate costs?
Asterand (Detroit/Royston, UK) thinks it has a simple answer, at least in the case of antibody-based drugs, with an assay that tests for the antibody binding to disease targets, other than that which is intended, in human tissue.
The company highlighted the importance of such testing of drugs even before they enter human clinicals, due to a recent incident in the UK in a test of a drug candidate that caused what the company called “severe reactions“ in a group of six young men.
Dr. Alexey Glazyrin, one of the leaders of the Asterand scientific team, told Medical Device Daily that he didn't believe any other company is “doing a similar thing“ as the new Asterand test strategy.
“I don't see any evidence in the literature,“ Glazyrin said. “However, there are possible approaches to this problem, which possibly other people use. But ours is completely different.“
The assay uses an existing technology known as immunohistochemistry. With the assay, the unmodified antibody under consideration is used to stain a range of human tissue, with some containing the target protein or tumor as well as normal tissue representing different parts of the body. Some of these tissues may contain the target protein, and whether the target is being expressed in diseased or normal tissue can easily be determined, the company said.
“These antibodies theoretically bind to a very specific target,“ Glazyrin said. “However, no one can guarantee by animal testing that the antibody does not also bind to other cells in the human body. If this happens, a Type 2 allergic reaction can be triggered, with the immunity system launching a massive attack against the cells attached to the antibodies, as possibly happened with the drug in the recent British trial.“
The company hopes to have a “big paper“ published on the assay by the end of the year, but until then, those interested in the assay can look at a summary of the five scientists' work in Clinical Cancer Research, the journal of the American Association for Cancer Research (Philadelphia).
Thus far, the company can only show its results on the breast cancer drug, Herceptin, because the drug companies for whom Asterand has used the test involved use of proprietary technology. Herceptin is approved by the FDA and is on the market.
“We actually demonstrated the technique at a couple of meetings, and there was sufficient interest, and there was an article published,“ Glazyrin said.
Until now, he said that scientists didn't think it was possible to test antibodies in advance, due to background “noise.“
Glazyrin said the new test will be “increasingly valuable“ because of the growing number of human or humanized antibodies being used as drugs which are either already on the market or in the development stage. He said he would project “tens, if not hundreds“ of antibody-based drugs currently being tested for drug development.
Another important advantage for Asterand is that because the assay is only used on human tissue – such as those contained in Asterand's large tissue data bank – there is no need for FDA approval, since it poses no potential harm to humans, Glazyrin told MDD.
The costs to a company would be minimal for the test – only a “few thousand dollars, which compares to about $800 million that it costs to develop a drug,“ he noted.
If the test finds that an antibody – rather than just binding to a diseased state, also binds to the brain, heart or pancreas, for example – is potentially causing adverse effects, Asterand does not play a role in the decision-making as to whether a company continues into human testing.
Asterand defines its role as assisting companies, based on human tissue samples and data, to “discover, validate, optimize and qualify drugs before they go into the clinic,“ said company CEO Randal Charlton.
“We understand that animal testing plays an important role in drug development, but mice – or in the recent case [in the UK], monkeys – are not men, and the case for including research based on human tissue and data is becoming increasingly compelling,“ Charlton said.
Charlton also noted that while there are currently no “firm requirements“ on drug companies to use human tissue research in 'Phase 0' drug development, the FDA is “increasingly recommending its use.“
“I think every antibody-based [drug] should be tested this way,“ Glazyrin said.