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ICAAC: Three-Drug Cocktail Aimed at Resistant Flu
By Michael Smith, North American Correspondent, MedPage Today
Published: September 16, 2009
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco.
SAN FRANCISCO -- A three-drug combination aimed at flu appears to overcome drug resistance -- at least in the test tube.
The three drugs -- amantadine (Symmetrel), ribavirin, and oseltamivir (Tamiflu) -- display an unexpected synergy when used together, according to Mark Prichard, PhD, of the University of Alabama Birmingham.
In a series of laboratory experiments, the triple-drug combination -- dubbed TCAD -- successfully inhibited both amantadine-resistant and oseltamivir-resistant viruses, Prichard said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
One unexpected finding, Prichard said, was that amantadine contributed to the effect even when used against virus strains resistant to the drug.Action Points
The synergy was seen in both seasonal and pandemic H1N1 strains, he said, as well as H3N2 seasonal flu and the highly pathogenic H5N1 avian influenza strain.
The use of triple combinations is common in other diseases, according to Karen Bush, PhD, of Indiana University in Bloomington. Bush, a member of the meeting's program committee, was not part of the study.
For instance, she said, both HIV and Helicobacter pylori are commonly treated with three drugs, usually from different classes, with the hope that a three-pronged attack will be more effective than single or double dosing.
When such drugs are taken over a long period of time -- as in HIV infection -- there is a potential to develop a virus that is highly resistant to several types of drugs, she said.
But in the case of flu, the TCAD combination would probably be only used in the setting of acute illness and only for a few days, which should minimize that risk.
"I would certainly not use it prophylactically," Bush said.
Indeed, Prichard said, the three drugs attack different targets, which should increase the genetic barriers to resistance.
Amantadine blocks the influenza M2 protein, which is involved in fusion of the virus to the cell, while oseltamivir blocks the enzyme neuraminidase, which plays a role in letting new viral particles escape from an infected cell.
Ribavirin -- not usually used against the flu -- interferes with viral replication, Prichard said.
Although the data are derived so far only from in vitro testing, the researchers do not expect any safety issues, according to co-author Amy Patick, PhD, of Adamas Pharmaceuticals, which is developing the combination.
All three drugs are known to be very safe, and because they have different mechanisms of action and are cleared using different pathways, there should be few interactions, she told reporters.
The company is currently performing animal experiments, and is enrolling 250 volunteers in South America -- still in its flu season -- for a clinical trial, she said.
The study was supported by Adamas Pharmaceuticals, which is developing the compound.
Prichard did not report any conflicts.
Primary source: Interscience Conference on Antimicrobial Agents and Chemotherapy
Source reference:
Nguyen J, et el "Triple combination of amantadine, ribavirin, and oseltamivir restores in vitro activity of antiviral drugs against resistant influenza viruses" ICAAC 2009; Abstract V-537b
http://www.medpagetoday.com/MeetingCoverage/ICAAC/15998
By Michael Smith, North American Correspondent, MedPage Today
Published: September 16, 2009
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco.
SAN FRANCISCO -- A three-drug combination aimed at flu appears to overcome drug resistance -- at least in the test tube.
The three drugs -- amantadine (Symmetrel), ribavirin, and oseltamivir (Tamiflu) -- display an unexpected synergy when used together, according to Mark Prichard, PhD, of the University of Alabama Birmingham.
In a series of laboratory experiments, the triple-drug combination -- dubbed TCAD -- successfully inhibited both amantadine-resistant and oseltamivir-resistant viruses, Prichard said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
One unexpected finding, Prichard said, was that amantadine contributed to the effect even when used against virus strains resistant to the drug.Action Points
The synergy was seen in both seasonal and pandemic H1N1 strains, he said, as well as H3N2 seasonal flu and the highly pathogenic H5N1 avian influenza strain.
The use of triple combinations is common in other diseases, according to Karen Bush, PhD, of Indiana University in Bloomington. Bush, a member of the meeting's program committee, was not part of the study.
For instance, she said, both HIV and Helicobacter pylori are commonly treated with three drugs, usually from different classes, with the hope that a three-pronged attack will be more effective than single or double dosing.
When such drugs are taken over a long period of time -- as in HIV infection -- there is a potential to develop a virus that is highly resistant to several types of drugs, she said.
But in the case of flu, the TCAD combination would probably be only used in the setting of acute illness and only for a few days, which should minimize that risk.
"I would certainly not use it prophylactically," Bush said.
Indeed, Prichard said, the three drugs attack different targets, which should increase the genetic barriers to resistance.
Amantadine blocks the influenza M2 protein, which is involved in fusion of the virus to the cell, while oseltamivir blocks the enzyme neuraminidase, which plays a role in letting new viral particles escape from an infected cell.
Ribavirin -- not usually used against the flu -- interferes with viral replication, Prichard said.
Although the data are derived so far only from in vitro testing, the researchers do not expect any safety issues, according to co-author Amy Patick, PhD, of Adamas Pharmaceuticals, which is developing the combination.
All three drugs are known to be very safe, and because they have different mechanisms of action and are cleared using different pathways, there should be few interactions, she told reporters.
The company is currently performing animal experiments, and is enrolling 250 volunteers in South America -- still in its flu season -- for a clinical trial, she said.
The study was supported by Adamas Pharmaceuticals, which is developing the compound.
Prichard did not report any conflicts.
Primary source: Interscience Conference on Antimicrobial Agents and Chemotherapy
Source reference:
Nguyen J, et el "Triple combination of amantadine, ribavirin, and oseltamivir restores in vitro activity of antiviral drugs against resistant influenza viruses" ICAAC 2009; Abstract V-537b
http://www.medpagetoday.com/MeetingCoverage/ICAAC/15998
