E-mail
the Coalition
COMPANY INFORMATION (To come)
MEETING AND CALL
NOTES
Community Calls and
Meetings with Boehringer Ingelheim
December 19, 2001
Keri Oberg
HIV Community Relations Specialist
Boehringer Ingelheim
Dear Keri, et al:
Pursuant to our teleconference on December 12, 2001, we are submitting herewith an amended proposal for a two phase compassionate use and expanded access program. (Please distribute internally as appropriate.)
I. TIPRANAVIR EXPANDED ACCESS (EA) PROGRAM PROPOSAL
The Coalition for Salvage Therapy ("CST") believes that the best and most compassionate expanded access program would be one which follows the model established with pharmaceutical companies in the last half decade or so, which includes Gilead Sciences Adefovir program, GlaxoSmithKline's Abacavir and Amprenavir programs, Abbott's Kaletra (ABT-378) program and most recently Gilead Sciences Tenofovir program. We agree that the intent, purpose and principle behind any expanded access program is to provide drug to individuals based on need. Almost without exception, these programs ultimately made drug available based solely on need, without arbitrary inclusion/exclusion criteria based on CD4+ count and viral load and which addresses the needs of the more advanced or treatment-experienced patient, who might otherwise not qualify for the clinical trials.
The operative definition and principle behind all recent EA programs is and should always be:
Any HIV positive person who has virologically failed/is failing or was/is intolerant to more than one protease inhibitor-containing regimen, irrespective or CD4+ count or viral load who, in the opinion of his health care provider, needs this drug in order to construct a viable treatment regimen.
However, under extraordinary circumstances and when it has been established that the drug supply initially require some limitations to the scope of the program, we have had to accept a triage approach for a short period of time -- a two-tiered program, beginning with "compassionate use", which seeks to place the neediest patients at the head of the line, at the start. As soon as production and manufacturing processes ramp up, the CST expects the implementation of a broader expanded access program.
You have recently proposed a broad expanded access program
to initiate 3rd Quarter 2002. We, instead, request that a limited
compassionate use program initiate at an earlier date, to be expanded
as rapidly as possible, as drug supply increases. We believe that
both stages of the program should be predicated on patient need,
rather than based on theoretical or proven
efficacy of the drug in specific populations (as outlined below).
A. First Phase - Compassionate Use (CU) Program - limited drug supply
B. Second Phase - Broad Expanded Access (EA) Program
While it would undoubtedly be advantageous if patients receiving
TIPRANAVIR could simultaneously have access to one or more additional
new or experimental agents at the same time to create the "freshest"
possible regimen, this cannot be a requirement of the program.
No one can guarantee that two or more experimental agents can
be made available through expanded access in a particular time
frame. The need to construct a drug regimen with previously unused
agents, however desirable, must be addressed as a matter of education
and recommendation, and not as an inclusionary/exclusionary
requirement. While it is the goal to successfully bring two or
more agents into use simultaneously, access to TIPRANAVIR should
not be delayed in pursuit of this goal. The company should direct
physicians to the Health and Human Service (HHS) guidelines which
advise against adding only one new drug to any proposed new regimen.
II. SALVAGE PROTOCOLS
The Coalition for Salvage Therapy has considered many different examples of clinical trial designs for salvage therapy. Obviously this is not a trivial issue. The complications of treatment and research in persons who have failed multiple antiretrovirals affect all aspects of trial design, including the nature of appropriate controls, blinding, treatment allocations, on-trial clinical management, eligibility, appropriate endpoints, duration of follow-up, and many other aspects.
Trials in heavily pretreated patients have some unusual accrual
issues as well. Patients have great motivation to try and get
experimental treatments, yet their health is more precarious,
so the risk/benefit balance seen in any clinical trial has some
unusual features. Although patients urgently need new therapies,
there are concerns about "using up" the few new options
out there
by combining them with sub-optimal background therapy. When patients
have "one shot", it is prudent to try and make that
effort as effective as possible. This especially complicates designs.
Control treatments are harder to construct and potentially may
not just be ineffective, but may prejudice later care.
Some key points came up again and again in our discussions, and they are worthy of note. For the sake of this synopsis, we will call heavily pretreated, and failing patients "salvage patients". We recognize that this term is unpopular, and will probably change at some point in the future.
The Coalition for Salvage Therapy (CST) has concluded that salvage protocols for heavily pretreated patients should include other promising experimental agents in clinical development. Thus, we strongly encourage Boehringer Ingelheim to begin discussions to explore and design collaborative studies, as soon as possible.
III. RESEARCH PRINCIPLES
Rather than propose individual and somewhat arbitrary individual protocols, the Coalition for Salvage Therapy instead asks that B/I agree to several general principles regarding the development of future protocols.
A. Salvage patients should not be exposed to monotherapy of
any kind, or to "virtual monotherapy", where one new
drug is added to a failing regimen for any appreciable length
of time. We recognize that pharmacokinetic studies, especially
of regimens containing more than one experimental drug are important.
But we urge that whenever possible, PK should be done in HIV
negative patients. When the participation of salvage patients
is required, exposure should be restricted to no more than two
weeks.
B. We are very encouraged by various sponsors' consideration
of collaborative research, where more than one experimental agent
might be used. Such treatment strategies offer the best hope for
salvage patients. We recognize this to be a difficult strategy
to implement. Corporate dynamics and regulatory barriers have
made this virtually impossible in the past. The
Coalition is committed to help build those bridges where necessary,
and to work with FDA and other regulatory bodies to help facilitate
this cooperation.
C. The coalition recognizes that a wide variety of research designs are necessary to get a full picture of any treatment's risks and benefits. Studies looking at both activity and efficacy provide a fuller picture of a treatment or strategy's attributes. Without prejudicing other designs, there is a minimal set of data we would like to see in regard to any new treatment.
IV. SALVAGE PROTOCOL EXAMPLE FOR MULTI-PI AND NNRTI-EXPERIENCED PATIENTS
TIPRANAVIR + Background Therapies of Patient's Choice*
vs
Kaletra (or T-20 or Atazanavir) + Background Therapies of Patient's
Choice*
vs
TIPRANAVIR +Kaletra (or T-20, or Atazanavir) + Background Therapies
of
Patient's Choice*
* will consist of the best new treatment regimen a patient can create.
We are cautiously excited about the willingness of several companies to consider collaboration with competitors. Previous efforts, such as the ICC, have shown mixed results. As community members and advocates, we will be glad to help facilitate such cooperation wherever possible. Our hope is that a consistent set of research principles and design templates will inform all of these efforts, so better to compare findings, and to assemble an overall view of our successes and challenges. We look forward to an ongoing dialogue on these issues.
Sincerely,
Coalition for Salvage Therapy
Revised January 9, 2002