Pfizer recruiting for phase II dose-finding trial for investigational compound offering no safety net: ”The trial design should be changed or otherwise stopped“, declares Mauro Guarinieri, Chairperson of the EATG.

”Pfizer’s trial is not ethical for people living with HIV“, strongly warns Nikos Dedes, Greece, Chairperson of the European Community Advisory Board (ECAB), the treatment working group of the European AIDS Treatment Group (EATG). ”The trial design should be changed or otherwise stopped“, declares Mauro Guarinieri, Chairperson of the EATG. ”We demand all concerned regulatory authorities to assume their responsibility and act accordingly,“ adds Mr Guarinieri.

What causes these two well-known activists to make such strong statements is the fact that Pfizer, the world’s biggest pharmaceutical company, is implementing a trial for its investigational HIV drug whose design, according to activists, is unnecessarily putting people with HIV and with severe immune suppression at risk.

To summarise the situation, the A26 trial is a PhaseIIb/III study to define the dose, preliminary efficacy and safety of the CCR5 chemokine inhibitor known as UK-427,857, or maraviroc, in participants who have never taken treatment before. The inclusion criteria allow individuals to enter the trial regardless of their CD4 count and viral load. This includes people with CD4 counts below 200 and viral loads over 100,000 copies. According to this trial design, patients who are in vital need for a potent and well-proven antiretroviral treatment regimen will therefore be included in a dosefinding trial of an investigational compound.

Results from several well-known cohort studies have shown that such patients are more likely to develop an opportunistic infection and eventually progress to AIDS, and are therefore in vital need of a potent and wellproven antiretroviral treatment regimen. All existing treatment guidelines are in line with this recommendation. In addition to this, newly diagnosed patients with advanced disease are generally not in the best position to make an informed decision on participating in a clinical trial or not.

David Haerry, Switzerland, ECAB Co-Chair, says that ”there is currently little clinical data available (about 10-day monotherapy in a few dozen patients) for the anti-CCR5 compound being developed by Pfizer. It is totally unacceptable to treat naïve patients with severe immune suppression and high viral loads with a drug combination containing an investigational drug whose potency and ideal dose are still unknown“. Haerry stresses that a failure in this patient population, either due to potency or adverse events, has an important impact on both the physical and psychological well-being of the patient and may impair future treatment options.

Mr Dedes nevertheless clarifies that, ”the development of new ARV drug classes is essential to treat experienced patients in need of effective salvage regimens. But in the case of naïve patients, new drug classes are less urgent given the number of effective treatment options available.“ In the light of these considerations, the EATG has objected to the proposed phase II18 trial designs for the CCR5 inhibitors. Three companies are currently enrolling patients for this compound in phase II trials.

The phase II design for the Pfizer compound was discussed at a meeting between the leading European researchers, the EATG and National Community Advisory Board representatives in November 2004 in Glasgow where, according to the European activists, ”Pfizer committed to adapt the trial to those recommendations at a global level,“ says Mr Haerry.

The initial trial design was then challenged at a national level by several national community advisory boards and regulatory authorities. Other requirements imposed by the latter caused Pfizer to withdraw the trial from some of these countries (France and Germany) or to stop it (Spain). Pfizer still announced that they would proceed in recruiting for the initial trial design without offering the safety restrictions as they were recommended by the group who met in Glasgow.

Despite all these objections, recruitment for the trial is taking place in Belgium, Italy, Switzerland, and the United Kingdom.

The EATG denounces Pfizer’s move as irresponsible and ethically questionable.

Pressure and requests for the fast development of investigational compounds in the name of patients with no options or other competitive considerations cannot justify putting naïve patients’ health at unnecessary risk.

Press release sent by the EATG on April 11, 2005. For more information, please contact:

David Haerry, ECAB, Co-Chair (German, French, English) at + 41 797125759 or david@eatg.org

Nikos Dedes, ECAB, Co-Chair (English, Greek) at +30 694 4386560 or nikos@eatg.org

Joan Tallada, EATG, External Communications Officer (Spanish, English) at + 34 637 464 803 or joan@eatg.org

Mauro Guarinieri, EATG, Chairperson (Italian, English) at + 39 347 9631837 or mauro@eatg.org

EATN - European AIDS Treatment News, Volume 13, I – Spring 2005