terça-feira, dezembro 21, 2004
GAT e EATG preocupados com ensaios clínicos de fase II em doentes naive
The European AIDS Treatment Group have raised concerns to the Committee for Medicinal Products for Human Use of the EMEA, about a number of phase II studies on naïve patients for a new class of anti-HIV compounds, inhibiting CCR5.
Dr. Daniel Brasseur
Chairman of the CHMP, EMEA
7 Westferry Circus
London, E14 4HB, UK
cc: Dr. Per Nilsson, EMEA
Brussels, Tuesday, 20 December 2004
Dear Dr. Daniel Brasseur,
After our representatives raised similar concerns to the November 8th meeting of the Ad-hoc Group on Antiretroviral Medicinal Products we are writing to draw your attention to a serious ethical problem that the community of PLWHA (People Living With HIV/AIDS) in Europe has identified in the protocols of several phase II trials for a new class of anti-HIV compounds.
The type of compounds in question are inhibitors of the CCR5 co-receptor which the HIV virus uses to bind to, and infect CD4 lymphocytes. At present, Schering-Plough, Pfizer, and GlaxoSmithKline are competitively developing such compounds.
All three companies are about to start European phase II dose finding studies, that will be conducted in both experienced and naïve patients. The EATG (European AIDS Treatment Group) and several national patients’ organisations have been informed by the above-mentioned pharmaceutical companies about the designs of these trials.
Acknowledging the urgent need for new classes of drugs for the experienced population and improved versions of existing ones, we welcome rapid development of novel compounds. However, we are deeply concerned about the trials the three companies have designed for the treatment-naïve patients.
All three companies plan to include severely immune compromised people (below 200 CD4 cells) with no upper limitation for viral load values.
As you will be aware, results from several well known cohort studies have shown that such patients are in vital need for a potent and proven in terms of efficacy antiretroviral treatment regimen. All existing treatment guidelines are in line with this recommendation.
Currently, there is only scarce clinical data available (about 10 days monotherapy in a few dozen patients) for the anti-CCR5 compounds being developed by the three companies.
We think that it is ethically unacceptable to expose treatment-naïve patients with severe immune suppression and high viral loads to a drug combination, containing experimental medications, whose potency and ideal dosages are unknown yet. A failure to this patient population, either due to potency or adverse events, has a great and grave impact on both the physical and psychological well being of the patient.
Today, there are several drug combinations for treatment-naïve patients with severe immune suppression and high viral load values (>100.000 copies) that have been proven to be potent, safe, and easy to take (down to 2 pills QD). This fact renders the aforementioned trial designs obsolete.
We also think that the trial protocols and the informed consent should make clear reference to the recommendations of existing guidelines for the treatment of HIV-infection, such as the fact that treatment initiation is not normally recommended for people with more than 350 CD4 cells, and to the fact that potent and well proven antiretroviral treatment regimens are available and free in the European Union.
In addition, the virological stopping criteria of the three companies’ trial designs are not in line with those laid out by existing treatment recommendations in a number of different ways. We cannot accept that the standard of care offered to trial participants, due to the aforesaid stopping criteria, could in effect be inferior to that recommended for naïve patients in normal clinical practice.
It is our opinion that the three drug companies should first proceed with treatment-naïve HIV-positive persons who are not at a high risk of treatment failure and disease progression (>200 CD4 and viral load below 100.000 copies) before experimenting with the new drugs in more immune suppressed naïve HIV-positive persons at phase III.
The urgent need for fast development of the CCR5 compounds for patients with no treatment options, does not justify putting treatment naïve people’s health at unnecessary risk.
Given that the EMEA has the duty to make sure that clinical trials conducted with the aim of obtaining a European marketing licence are ethically sound  we call on you to issue a statement with regard to this issue and to include specific recommendations in the note for guidance on anti-HIV drug development, and we are prepared to meet with the CHMP and explain our concerns and proposals.
Chair, Board of Directors
European AIDS Treatment Group
 Article 16 of regulation EC 726 2004 states [that there is] “a need to provide for the ethical requirements of Directive 2001/20/EC of 4 April 2001 of the European Parliament and of the Council on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use to apply to medicinal products authorised by the Community.