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Passive Immunotherapy Drug: HRG214
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Here is a press release from the manufacturer, which is followed by the poster abstract reported at the XV Intl AIDS Conference.
Virionyx Corporation Ltd, the New Zealand biopharmaceutical firm presented a poster at the XV International AIDS Conference in Bangkok, Thailand (July 2004) on this potential therapy for HIV.
As the conference delegates grappled with the announcement that a preventative AIDS vaccine is still years away and with the United Nations report that 14,000 people are infected with human immunodeficiency virus (HIV) every day, the Auckland based company had some good news for them.
Virionyx told the doctors, researchers, scientists, medical professionals and media attending the conference that AIDS and HIV infected patients participating in the pre-Phase II multi dose clinical trials of its biotherapeutic, PEHRG214, at Harvard Medical School are responding favourably to treatment.
The international AIDS and cancer specialist, Associate Professor Bruce Dezube, who is conducting the trials, reported early signs of efficacy in the patients and that they generally tolerated the treatment well, in contrast to the existing AIDS drugs which have significant adverse side effects.
"The only adverse event was a rash -- a mild allergic reaction -- to the treatment in some of the patients. This was successfully prevented with Benadryl, Tylenol and Allegra on the days they were infused," he said.
Despite the low dosage levels of PEHRG214 used in the trials, Dr Dezube said many patients showed significant improvement in three vital areas -- a reduced amount of virus overall, an increase in the number of healthy CD4 white cells and a reduced number of infected white cells, which are the source of continuing infection in an HIV infected patient.
In his written summary of the trials for the conference, Dr Dezube said immune-based therapies, such as PEHRG214, may work to enhance conventional AIDS drug regimens or even play a key role in maintenance strategies that may eventually allow patients to stop taking drugs.
Back in New Zealand at the Virionyx Corporation laboratories Dr Frank Gelder, the company's Scientific Director who discovered the proprietary antibody therapy preparation, said he was pleased that the United States Food and Drug Administration (FDA) approved trials on over 40 patients at Harvard and elsewhere were reinforcing and extending the results previously observed with the drug in the compassionate release treatment of 77 patients, some of them in New Zealand, in the late 1990s prior to it entering the formal FDA trial process.
Dr Gelder explained that PEHRG214 is a new approach to AIDS treatment, using antibodies purified from immunised goat plasma to target specific parts of the HIV not recognised by the human immune system.
He said Virionyx maintains two special herds of goats that it uses to produce antibodies against HIV. These antibodies are then formulated by Virionyx's team of scientists for use in humans.
"Goats have immune systems that can recognise specific parts of HIV not recognised by the human immune system and mount an antibody response to these previously unidentified targets," Dr Gelder said. "I developed the science for this in the US and brought it to New Zealand because of the unique environment in this country where livestock herds carry a very low incidence of chronic endemic diseases, especially those with potential to transfer to man, and can therefore be utilised to develop antibodies."
Dr Gelder said under laboratory conditions PEHRG214 demonstrates the ability to destroy cell-free viruses.
"While currently available anti-HIV drugs taken in careful combination are very effective in controlling the ability of the virus to replicate and infect healthy CD4 white cells, sooner or later the virus mutates and escapes these treatment regimens. Trial data to date suggests PEHRG214 is effective even in patients who are failing the highly active anti-retroviral treatments known as HAART," he said.
Based on advice from Dr Dezube and other international consultants assisting with the trial of PEHRG214, the drug will now immediately proceed to a full US FDA compliant Phase II efficacy trial in 40 patients.
CONFERENCE ABSTRACT
"A Passive Immunotherapy, HRG214, in HIV-1 Infected Patients: a multidose study"
Bruce Dezebue, from Beth Israel Deaconess Medical Center/Harvard Medical School, reported these study results at the XV IAC.
HRG214 is a novel ployclonal antibody (Ab) preparation produced by immunization of goats with purified HIV proteins followed by booster immunizations with synthetic peptides to HIV epitode regions. The resultant agent has high titers and affinity to multiple HIV epitopes and inhibits abroad spectrum of primary HIV isolates. As previously reported (Jnl Infect Dis 2003) HRG, when administered intravenously as a single dose up to 16 mg/kg, is reasonably well tolerated, achieves plasma concentrations exceeding those values which neutralize HIV in vitro, and demonstrates antiviral activity.
Dezube said in his abstract that immune-based therapies may enhance the activity of conventional regimens or be part of innovative induction/maintenance strategies that may eventually allow the discontinuation of treatment while maintaining good virologic control and immune function. I say this is quite a leap by Dezube & prove it first.
A multi-dose study to assess the pharmacokinetics and safety of HRG was conducted in HIV-1 infected patients with entry CD4 counts >50 cells/ul and viral load >500 copies/ml; concomitant antiretroviral therapy was permitted provided the regimen was stable. HRG was administered at a dose of 4 mg/kg twice a week for a total of 9 doses over one month. Serial blood samples were obtained for HRG plasma levels, HIV viral load, and the presence of anticaprine Abs.
Eleven patients received HRG. Before receiving study drug patients had median 185 CD4s, HIV RNA 55,000 copies/ml, and 7 of 11 were taking HAART. The only adverse event judged probably related to study drug was a transient rash/allergy in 3 patients. The protocol was amended so that patients received pre-treatment prophylaxis with Benadryl, Tylenol, and Allegra; such pre-treatment decreased the incidence of rash. Median serum HRG half-life was 70 hours. In one patient, an increase in anti-caprine antibody levels was observed, accompanied by accelerated HRG clearance. Median decrease in VL was 0.20 log; maximal decrease >2.0 log was seen in a patient resistant to all drug classes. Two of eight patients had a decrease in HIV RNA levels of >0.50 log even though they were on HAART and failing virologically. Median (maximum) increase in CD4 cells were 27 (136) cells.
Dezube concluded HRG214, when administered twice weekly over the course of a month, is reasonably well-tolerated, achieves plasma concentrations approaching those values which neutralize HIV in laboratory experiments, and demonstrates early evidence of antiviral activity even in anti-retroviral experienced patients. Dose escalation study is ongoing. Dezube concluded further trails are warranted to explore dosing both at higher levels & for longer periods of time.
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