A new access program and registry developed by the American
Society of Clinical Oncology to facilitate use of off-label cancer
drugs could serve as a model for independent bodies that could manage early
access to experimental therapies, even though ASCO itself is not tackling
ASCO's initiative is designed
to match off-label targeted cancer therapies to individual patients likely to
benefit based on the genomic profile of their tumors, while collecting data
about new uses for approved drugs.
"We should develop
programs to make it easier to access drugs, but require more detailed reporting
of outcomes, which is just the opposite of the current situation," CMO
Richard Schilsky told BioCentury. "Doing so would provide treatment
options to patients in need and allow us to learn from all these patient
Like programs that grant early
access to experimental medicine, or compassionate access, ASCO plans to limit
its off-label initiative to patients who are not eligible for trials and who
have no alternatives.
A central feature of the
program is the establishment of an honest broker to make decisions about the
allocation of targeted therapies and to collect and analyze outcomes data.
If the project is successful
for off-label therapies, it could inspire similar schemes based on honest
brokers affiliated with medical specialty societies that would serve as
intermediaries between drug companies and patients seeking early access to
PhRMA, BIO and their member companies, as well as
patient organizations and congressional staff, are all engaged in separate
discussions - primarily behind closed doors - about creating new policies to
facilitate equitable early access to experimental therapies.
As BioCentury proposed in a
March 31 Commentary, the creation of independent third parties is one of
several options under consideration.
To be successful, early access
policies will have to be aligned with several social and scientific trends:
social media-fueled patient empowerment; the development of highly effective
targeted therapies made possible by the integration of molecular diagnostics
into drug development and clinical practice; and a "right to try"
movement that is gaining traction among state and federal lawmakers.
Access and registry
According to Schilsky, ASCO's
program was prompted by the realization that many oncologists lack the
expertise required to make treatment decisions based on genomic test results,
as well as the difficulty patients face in getting reimbursement for off-label
"I'm reacting to the rapid
penetration of genetic profiling in the cancer patient population, with many
comprehensive cancer centers, community hospitals, and commercial labs setting
up to do multiplex testing," Schilsky said. Interpreting tests results to
determine whether a specific genomic variant is clinically actionable is "challenging
even for experts," he added.
Physicians would submit a
genomic profile of a patient's tumor from a CLIA-certified lab, along with a
proposed treatment plan and request for off-label use of a targeted therapy, to
an honest broker. The dosing and regimen would be consistent with labeling for
To facilitate such requests,
ASCO is considering establishing an Internet-based "tumor board" of
clinical oncologists and molecular pathologists that would review genomic test
results and provide advice to physicians, including potential treatment
The honest broker would review
the application. For approved applications, the honest broker would arrange for
shipment of a three-month supply of the drug. The patient's response would be evaluated
and, if appropriate, additional supplies would be dispensed.
Schilsky said he is "writing
a clinical protocol for what will essentially be an observational study."
The protocol will be "for
patients who have exhausted all treatment options, but who have reasonable
performance status, so they have a meaningful chance of benefiting from therapy
if benefit can be derived."
In addition to validating
treatment plans, the honest broker would maintain a registry with information
about patient characteristics and outcomes.
ASCO is speaking with several
for- and not-for profit entities that could serve as the honest broker,
He noted that clarity about the
rules will be key to making an honest broker acceptable to patients and the
"Any time a third party
makes a decision, that decision has to be made according to prespecified
guidelines," he said. "It has to be transparent, and as objective as
possible - and people have to understand going in there will be some cases that
will be rejected."
Drug companies will be asked to
supply off-label drugs at no cost, and insurance companies will be asked
to pay for all other treatment expenses, Schilsky said. In return, drug
companies and payers would benefit from the generation of data about off-label
Schilsky has approached six
pharmaceutical companies to discuss the project. "All have expressed
interest in the idea. None said they are definitely in," he said. "No
one has said no."
Schilsky said he also has
presented the concept to "a couple of insurance companies. The general
response has been: 'We are OK paying for the healthcare costs as long as we don't
have to pay for the expensive drugs.'"
Schilsky also has discussed the
concept with senior FDA officials.
"FDA feels that if
something like this was set up, it would enhance their understanding of how
these drugs are being used. FDA may turn out to be a champion of this kind of
approach," he said.
Schilsky said ASCO hasn't
determined how much the project will cost or how much demand there will be.
"We plan to start this as
a pilot project with a limited number of physician practices scattered around
the country, with as many drugs as we can get into the program initially,"
he said. "We want to see if this is feasible, if we can we get the drugs
to patients in a reasonable period of time, if there are any significant
patient benefits from the approach, and if can we get the necessary data from
ASCO hopes to get the pilot
running before year end.
In a paper describing the
program in Nature Reviews Clinical Oncology this month, Schilsky
mentioned the possibility of including investigational drugs. But he told
BioCentury ASCO has decided to stick with approved drugs.
"It was a question of not
biting off more than I could chew. Once you get into investigational drugs, you
get into a higher level of complexity regarding human subject participation and
regulatory oversight," he said.
"There are at least 25
marketed targeted anticancer treatments that hit 15 or so different genetic
targets," Schilsky added. "We already have a good starting point of
the universe of marketed drugs without having to get into investigational
ASCO's project is inspired in
part by the growing sophistication of patients who read about targeted
therapies on the Internet and request access to off-label therapies, Schilsky
Patient demand that is the
result of social and news media reporting about new therapies is also propelling
discussions among life sciences companies about policies for providing early
access to experimental drugs.
"It feels like a pivot point" for early access, said
Amrit Ray, CMO at Johnson
& Johnson's Janssen Pharmaceuticals division. "It is positive
to have great innovation for patients. It is positive to have empowerment of
patients sharing information, with the ability to ask questions and be in
J&J recently revised its
policies on early access to investigational drugs, Ray said. The most visible
result is a web page with clear information about accessing investigational
drugs with contact information for physicians to request access (see
Featured Links, A11).
"We stepped back and made
sure the information on how to make a request was accessible in one place, with
one phone number and one email address," Ray said. "We made sure
those requests go to one common place and are quickly addressed by therapeutic
area and disease experts."
He added that policies will
need to adapt to the changing environment.
"When it comes to policies
and frameworks for early access, we have to get in the mindset of continuously
revisiting those approaches," said Ray. "Science is changing,
patients are changing, and it makes great sense that approaches and frameworks
for early access will evolve and change."
Ray said J&J is participating in discussions on early
access policies at BIO and PhRMA, and he will participate in a closed meeting
on early access at the Brookings
The April 29 workshop is being
organized by Darshak Sanghavi, who is Merkin fellow and managing director of
economic studies at Brookings' Engelberg Center for Health Care Reform.
Sanghavi told BioCentury the
informal meeting is "primarily geared to identify common issues and
experiences from major pharma companies, with the goal of identifying some
themes that might be addressed in a formal, larger meeting to address
compassionate use with a larger group if there is interest."
In addition to pharma company
executives, the meeting will be attended by a bioethicist and a patient
Speaking on BioCentury This
Week television, Sanghavi said there is a need to collect some basic
information in order to craft new early access policies.
"If we don't even know the
magnitude of the issue, then we really can't even decide how we're going to fix
it," he said (see BioCentury This Week, April 13).
Nancy Goodman, founder and executive director of the advocacy
v Cancer, added that better policies probably would lead to more
widespread access to investigational drugs.
"I suspect, frankly, that
there are fewer compassionate uses issued than we as a society might want,"
Goodman endorsed the creation
of organizations that are independent of drug manufacturers to review
applications for early access. Such decisions could be made by a "third
party that would be responsible for reviewing every case on an expedited basis,
understanding both the challenges and limitations the company faces, and the
probability of a particular investigational drug assisting a patient," she
Sanghavi suggested third party
decision makers could absorb some of the administrative tasks and costs that
are barriers for small companies to offer early access.
"It seems to me that the
biggest cost is really the evaluation, the paperwork, maybe tracking [outcomes
and] not really the manufacture of the drug, at least with limited exceptions,"
he said. "All of us can agree that the last thing we want to do is to
impose additional regulatory burden and cost on people who are trying to make
Right to try
Publicity about recent efforts
by patients to obtain access to unapproved drugs, including the successful
social media campaign launched by Josh Hardy's family, may have revived
the fortunes of the "right to try" movement.
Last week, the Arizona Senate
passed HCR 2005, a bill that would allow physicians to prescribe
investigational products to eligible terminally ill patients who have no "comparable
or satisfactory" FDA-approved treatment options.
The bill will be placed on the
ballot for voter approval in November unless Gov. Janice Brewer vetoes it.
If the initiative passes, it would be possible for patients to
receive access to experimental drugs with the consent of their physician and
the drug manufacturer. FDA would have no oversight role, according to Christina
Corieri, healthcare policy analyst at the Goldwater
Institute, a libertarian think tank that drafted the legislation.
Just as the federal government
has opted to exercise enforcement discretion in the face of state marijuana
laws, it could choose to allow Arizona, and any other state that enacts a
similar law, to make experimental drugs available to terminally ill patients
without FDA oversight, Corieri said.
If FDA asserts federal
preemption to prevent implementation of the law, the Goldwater Institute is
prepared to litigate the case, she said.
"We believe the right to
save your own life is a fundamental right protected by the Constitution,"
According to Corieri, a 2006
ruling against the right to access experimental drugs, issued by the U.S. Court
of Appeals for the District of Columbia Circuit, "is not binding on any
other circuit" and does not apply in Arizona.
The case was filed by the Washington
Legal Foundation (WLF) and Abigail
Alliance for Better Access to Developmental Drugs (see BioCentury,
Jan. 21, 2008).
Bills similar to HCR 2005 are
pending in Louisiana and Missouri.
More sweeping legislation has
been introduced in the U.S. Congress. The Compassionate Freedom of Choice Act
(H.R. 4475), sponsored by Rep. Morgan Griffith (R-Va.), would allow
manufacture, importation, distribution and sale of investigational products
outside of a clinical trial for terminally ill patients without restriction by
or reporting to FDA.
H.R. 4475 provides liability
protection for investigational drug manufacturers; Arizona HCR 2005 does not
include liability protection.
Political support for right to
try legislation could accelerate efforts to craft new early access policies at
BIO and PhRMA, which oppose efforts to bypass FDA regulation of experimental
Alliance for Better Access to Developmental Drugs, Lorton, Va.
Society of Clinical Oncology (ASCO), Washington, D.C.
Industry Organization (BIO), Washington, D.C.
Institution, Washington, D.C.
Institute, Phoenix, Ariz.
& Johnson (NYSE:JNJ), New Brunswick, N.J.
v Cancer, Washington, D.C.
Research and Manufacturers of America (PhRMA), Washington, D.C.
Legal Foundation (WLF), Washington, D.C.