After getting important feed back from several key activists and assessing the main issues facing patients trying to access multiple active agents for their survival, SalvageTherapies.org sent the following document to all pharmaceutical companies involved in the development of HIV medications that may be effective for people with three drug class resistance.
1- Patients with 3-DCR HIV should not be exposed to monotherapy of any kind,
or to “virtual monotherapy”, where one new agent is added to a failing regimen.
2- We recognize that pharmacokinetic (PK) clinical trials including the study
of agents administered individually and as a component of a multiple-drug
regimen, are extremely important. Whenever possible, PK evaluations should
be conducted in HIV-negative study volunteers. When the participation of patients
with 3-DCR HIV is required, exposure to the experimental agents should be
limited to a time period that will not lead to resistance to the study drug.
If such period is not known, patients should be clearly informed about the
potential risks for resistance in the respective study consent forms.
3- We strongly encourage collaboration among the various pharmaceutical companies
with antiretroviral agents in development to perform early interaction studies
so that lack of interaction data does not represent a barrier to performing
phase III combination studies and expanded access programs that allow the
use of more than one investigational agent. The U.S. Food and Drug Administration
(FDA) has also expressed support for this initiative, as it represents the
greater hope for heavily treatment-experienced patients.
4- No unnecessary exclusion criteria should be placed on studies unless there
is a strong indication of considerable risks to the well-being of the target
population. Examples include exclusions of patients with chronic hepatitis
B virus (HBV) or hepatitis C virus (HCV) coinfection, patients with CD4+ cells
counts below 50 cells/mm³, and exclusion of Fuzeon (T-20) or other agents
in the same phase of development due to lack of interaction data.
5- We recognize that an extensive clinical research program is necessary to
determine the clinical utility of an experimental agent, including its various
risks and benefits. Here is an overview of the minimum requirements to be
satisfied in order to advocate for the approval and use of an experimental
agent:
a. PK interaction studies prior to the implementation and enrollment of phase
III studies that include all approved and experimental agents in the late
stages of development which are most likely to be used in combination with
the study drug, opportunistic infection prophylaxis, methadone, and contraceptive
hormones. Other interaction data including psychotropic agents, lipid-lowering
agents, anti-hypertensive treatments, antacids and agents used for gastric
reflux, antiseizure medications, and erectile dysfunction treatments should
be obtained prior to FDA approval;
b. Enrollment of people of color, women and other under represented populations
should be given high priority, including in pivotal PK studies and phase II/III
clinical efficacy studies. Several PK studies have indicated possible sex
and gender based differences in drug metabolism that may affect dosing decisions.
c. When considering studies of combination experimental agents, emphasis should
be placed on regimens employing two distinct characteristics: regimens that
are most likely to be successful, and regimens that are most likely to be
used in the “real world.”
6- Proactive expanded access program (EAP) discussions should begin early
with community consultation. The following important considerations should
be taken into account:
a. EAPs should be implemented as soon as dosing, safety, efficacy and interaction
data from phase II A/B studies are available.
b. EAPs should always facilitate access to more than one active agent and
to other experimental agents that have been studied in previous interaction
studies that are in or near Phase III development.
c. The use of approved agents should not be excluded unless a safety or interaction
issue is clearly present.
d. Companies should plan in advance to minimize any drug supply limitations
that would prevent early access for people with the greatest clinical need
who cannot construct a viable regimen. When drug supply limitations are an
unavoidable issue, we recommend a staged process that offers access to those
with less than or equal to 100 CD4 cell count and that works up to higher
or no CD4 cell count limitation when supply permits. This staged EAP should
be preformed with community consultation and regular intervals of status notification
to the community, including number of patients screened, enrolled, and on
waiting lists.
e. Whenever possible, EAPs should be made available to those patients who
have screened out of phase III studies and/or those with geographical limitations
that prevent their participation in studies.
f. EAPs should not be site specific and should include community clinics that
treat uninsured patients. No geographic limitations should be present for
patient access.
g. Companies should optimize the EAP paper work process to enable physicians
with busy practices to use the program without road blocks. It is suggested
that a national institutional review board (IRB) should be used to minimize
local IRB complications