right-to-try laws, which have been signed by a Democratic governor in Colorado
and a Republican in Louisiana, are responses to deep dissatisfaction with the
pace of drug development and frustration with the ways biopharma companies have
responded to pleas for early access to experimental drugs.
The two new
laws, and similar bills pending in other states, are based on model legislation
drafted by the libertarian Goldwater Institute. They
are promoted as giving patients with life-threatening conditions and no
alternatives the right to access experimental drugs early in the development
process - without enrolling in clinical trials or seeking FDA
rather than creating new rights for patients, the initiatives actually attempt
to create rights for drug companies to provide experimental drugs outside the
framework of FDA regulation.
The RTT laws
will be effective only to the extent that the underlying assumption is correct:
that FDA is the principal barrier to accessing experimental drugs. To benefit
patients, the laws must also withstand possible legal challenges, and biopharma
companies must be willing to rely on state law to bypass FDA oversight.
assumptions are being put to the test now in Colorado and Louisiana, and the
experiment will likely expand as a dozen or more states are likely to enact RTT
laws over the next year.
It is unclear
whether the state laws will deliver on their promises to patients, but coming in
the wake of several high-profile compassionate access campaigns, they are
certainly focusing the attention of FDA leadership, the biopharma industry,
patient advocates and members of Congress on the need to improve access to
House Bill 1281, which added an article to state law on access to treatments
for terminally ill patients, passed both houses of the state legislature on
voice votes with no opposition. It was signed into law by Gov. John
Hickenlooper, a Democrat, on May 17.
model legislation drafted by the Goldwater Institute, the Colorado law says
patients with terminal illnesses "do not have the luxury of waiting until
an investigational drug, biological product, or device receives final approval
from the United States Food and Drug Administration."
It adds that
these patients "have a fundamental right to attempt to pursue the
preservation of their own lives by accessing available investigational drugs,
biological products, and devices."
To be eligible,
patients must have a terminal illness, have "considered all other
treatment options currently approved" by FDA, be unable to participate in
a clinical trial for the terminal illness within 100 miles of their home, or
not have been accepted into a trial within one week of completing an
must also receive a written recommendation from a physician for the
applies to compounds that have "successfully completed" a Phase I
trial, remain "under investigation" in an FDA-approved trial, and
have not been approved for marketing.
law frees insurers and providers of any obligation to pay for the experimental
compound or treatment associated with its use.
law, manufacturers are under no obligation to provide access to investigational
In a May 30
statement announcing his signature on Louisiana's Right to Try Act, House Bill
891, Gov. Bobby Jindal, a Republican, said individuals with terminal illnesses "should
have every opportunity to live life to the fullest and that is often possible
through experimental drugs or treatment."
also noted the "Goldwater Institute supported the bill and is currently
working with legislators in nearly two dozen states to pass or introduce the
Right to Try Act."
legislature unanimously passed an RTT bill in May. Gov. Jay Nixon, a Democrat, has not indicated whether he intends
to sign it into law.
legislature has voted to submit an RTT law to voters as a ballot initiative in
The RTT laws
that have been enacted and introduced are vague or silent about several
important issues. For example, while they allow access following a Phase I
trial as long as a Phase II trial is under way, they do not have provisions for
withdrawing access if unanticipated safety issues are discovered, or if there
is a definitive determination that a product is not effective.
They also do
not require the systematic collection, reporting or dissemination of outcomes or safety data that could help physicians and
patients make decisions about using an experimental drug.
One of the
premises of the RTT movement is that a plethora of effective compounds is
languishing at biopharma companies that could extend or save lives if patients
Goldwater Institute designed the Right to Try Act because there are over a
million Americans dying every year of terminal illness and there are many drugs
that could be lifesaving, but they're locked out of the process to access them,"
spokesperson Lucy Caldwell said in an interview broadcast on BioCentury
This Week television. "The Right to Try Act
is going to change all that. It's going to fix the broken system by allowing
terminally ill patients, with their doctors, to gain access to experimental
treatments that could save their lives."
also say FDA has set the hurdles too high for demonstrating safety and
efficacy, especially for life-threatening conditions that have no adequate
acknowledged that allowing RTT access could negatively affect clinical trials,
and suggested this would be a good thing. "Instead of asking whether Right
to Try is going to negatively impact our backward, double-blind clinical trial
process, what we should be asking is why we have a double-blind clinical trial
process in this country that locks dying patients out of drugs for a decade
plus," she said.
suggested FDA's public posture on compassionate access is deceptive. The agency
says it approved 99.4% of expanded access applications submitted from October
2009 to September 2013.
Caldwell, "many drug companies are singing a different tune." In
private discussions with the Goldwater Institute, she said, companies report it
is "very hard to get the FDA to be cooperative when they're trying to get
drugs to patients."
declined to identify the companies.
Steve Walker of the Abigail Alliance, FDA's statistics
account only for "completed IND applications for access, not requests for
access." Walker co-founded the alliance, which advocates for early access
to experimental drugs.
number of completed applications is a small (in fact almost certainly tiny)
fraction of the number of requests," Walker told BioCentury in an email. "The
hurdles for completing an IND application for even a single patient cause the
number of completed ones to be exceedingly small. The actual number of
requests, depending on how they are defined, would be in the many thousands to
FDA, and many tens of thousands or even hundreds of thousands every year"
to physicians and companies.
chairman and CEO of Amicus Therapeutics Inc.,
and the father of two children with the rare lysosomal storage disorder Pompe's
disease, doesn't think FDA blocks access to experimental drugs.
been down this road many times, and I've always found the FDA very open to
expanded access and compassionate access protocols," Crowley told
BioCentury. "I haven't seen an instance where a patient wanted access, a
company wanted to provide it, a physician recommended it, an IRB was good with
it, and FDA said no. More often than not it is the companies that say no."
FDA has not
taken a position on state RTT laws, and Commissioner Margaret Hamburg told
BioCentury she will not speculate about whether the agency would challenge them
or attempt to dissuade companies from making experimental drugs available
outside the agency's jurisdiction.
express skepticism that the laws will help patients.
sure the kinds of approaches the laws are outlining are really the things that
will make the most difference for patients," she told BioCentury.
think we are a barrier to access for patients; often we are a facilitator,"
Hamburg added. "We can often be an advocate for the patient with the
company. The company at the end of the day has to make the decision, and there
have been a number of instances where we have moved the company toward making
the treatment available for a given patient."
Hamburg, state RTT laws and media attention on compassionate access requests
have prompted FDA to consider whether it could help improve access to
experimental treatments. "The conversation around expanded access has been
brought into greater focus by the activities at the state level and continued
concerns and effort by patients to get access to experimental therapies that
are not through the review process," she told BioCentury.
Patient advocates split
patient advocates are on board. The notion that clinical trials should be
circumvented worries Diane Dorman, VP for public policy at the National Organization for Rare
Dorman told BioCentury This Week television that providing access to
investigational drugs after Phase I is "really unsafe."
access to a compound should occur after it is in "Phase II, and in patient
populations that are affected by this particular condition, to see if it
actually works, because we want to make sure that the clinical trials are
conducted in an efficient [manner] and as speedily as possible, to get these
therapies to the patients, to wider populations, as quickly as possible."
Hogan, the mother of a child with the rare lysosomal storage disorder mucopolysaccharidosis
II (MPS-II, Hunter syndrome) and a rare disease advocate, also opposes RTT
laws, but for other reasons.
RTT laws are "a
double negative for patients because they won't improve access to
[experimental] drugs, and they take away from the work that actually needs to
be done, which is improvement of the compassionate use system," Hogan told
and Louisiana laws "give people false hope because there is no right
created by the laws," she added. "They are not much different from
the current system" because decisions about granting access will continue
to be made by drug companies.
do not want to provide their drugs, and right to try does nothing to change
that," according to Hogan.
Hogan also is
critical of provisions in RTT laws that limit access to patients with
immediately life-threatening illnesses because patients like her son who have
fatal, progressive diseases might not qualify.
provisions allowing patients who live more than 100 miles from a trial site to
access experimental drugs "don't reflect the reality of the world of rare
diseases," Hogan said. "For rare diseases, there is hardly ever a
clinical trial within 100 miles."
provisions could make it impossible to test Orphan drugs because too many
patients would opt for access under RTT, she said.
disagrees, however, with Dorman's contention that compounds should not be made
available based on Phase I data. "Should certain drugs be available after
Phase I? Yes, if the risk to the patient [from the disease] is equal to or
greater than the risk of the drug," said Hogan.
that for life-threatening conditions, especially rare diseases, Phase I trials
can be conducted with patients who have the disease rather than with healthy
support RTT, even if they don't think the laws are perfect.
autologous mesenchymal stem cell therapies view state RTT laws as a path around
FDA regulation, according to SammyJo Wilkinson, a spokesperson for the advocacy
organization Patients for Stem Cells. In February, the
U.S. Court of Appeals for the District of Columbia rejected arguments that
autologous stem cell procedures are a "procedure of medicine" that
cannot be regulated by FDA.
us at Patients for Stem Cells have benefited from stem cell therapy, and even
though we are mostly chronic patients with illnesses like COPD, progressive MS
or cerebral palsy, we share the same no-hope scenario as terminal patients who
have no FDA-approved therapies," Wilkinson told BioCentury. "If the
FDA doesn't get heavy-handed with the states on RTT, this will at least save
some lives for the most vulnerable."
who would like RTT laws to include chronic diseases, added that Patients for
Stem Cells is lobbying for enactment of an RTT law in Georgia.
advocates hope state RTT laws will help tip the scales in favor of access for
children, who are often ineligible for clinical trials of novel drugs.
laws are a very good idea; they will help broaden access to drugs that might
help save children and other patients," said William Burns. Burns is the
uncle of Josh Hardy, an eight year-old whose life was saved because he received
access to Chimerix Inc.'s
brincidofovir as a result of a viral social media campaign.
BioCentury incentives should be created to encourage companies to provide
compassionate access, and FDA should provide assurances that adverse event
reports from compassionate access will not impede approval.
Burns is a
member of the Coalition Against Childhood Cancer, an
umbrella organization that coordinates the efforts of a number of pediatric
cancer patient advocacy groups.
is considering establishing a committee to screen requests to advocate for
compassionate access, Burns said.
needs to be a mechanism for patients who face life-threatening illnesses where
there is no FDA-approved drug to access investigational drugs," said
Jonathan Agin, a member of the coalition.
facing a crisis in this country in terms of science far outpacing drug
development because of the cost of commercialization, so overall I'm in favor
of right to try," Agin told BioCentury.
is prepared to dust off the playbook it used for Josh Hardy, according to
Richard Plotkin, a member of the board of directors of the Max
arranged for Josh's mother, Aimee Hardy, to appear on national television news
programs to publicize her plea to Chimerix to provide brincidofovir, and he
organized a social media campaign that reached at least 1.5 million people in
right situation arose, I would certainly call upon all the people I called on
before," Plotkin said.
trade associations have not taken formal positions on RTT, but they, along with
many of their members, have expressed skepticism about the bills.
CEO of GlycoMimetics Inc. and chair of BIO's board of
directors, said RTT laws that allow companies to bypass FDA are aiming at the
wrong target. "Because FDA generally does approve expanded or
compassionate use requests, I think they are trying to solve a problem that
doesn't really exist," she said.
think state RTT laws will provide patients better access to experimental
laws are more an employment act for lawyers than a right for patients," he
said. "I don't think anything [in the laws] compels a company in Colorado
or Louisiana to give a medicine. The company has to consent, so the law doesn't
solve that problem."
PhRMA is concerned the state laws try to
circumvent FDA oversight.
the industry in general have serious concerns about any approach that would
make an investigational drug available outside the oversight of the FDA and
that seeks to bypass the FDA and the clinical trial process," Sascha
Haverfield, VP for scientific and regulatory affairs at PhRMA, told BioCentury.
One company, Neuralstem Inc.,
told BioCentury it plans to offer its compound for amyotrophic lateral
sclerosis (ALS) under RTT, which it said will supplement, not replace, clinical
trials (see "Neuralstem's
Plan," page 6).
Haverfield and King don't think RTT laws will have their intended effects, they
agree the process for providing access to experimental drugs should be
right-to-try legislation, while well-intentioned, is unlikely to achieve the goal
of getting safe and effective medicines to patients as soon as possible,"
think needs to happen is all the stakeholders - patients, healthcare providers,
regulated industry, FDA and lawmakers at the state and federal levels - need to
look at how can we improve the expanded access process that is in place,"
suggested that FDA guidance indicating how the agency uses safety and efficacy
data from expanded access could reduce industry concerns that granting access
will have negative regulatory consequences.
said on multiple occasions that it has never failed to approve an application
based on an adverse event reported in expanded access," Haverfield said. "It
has not said that such reports have not led to additional clinical trial
requirements or requirements for additional trials based on data that is
extremely difficult to interpret."
added it would be far better to get life-saving drugs approved more rapidly.
to ask, does the urgency of the approval system we have in place match the
urgency of an immediately life-threatening disease? We need to ensure that the
urgency of the drug development and approval system matches patients' urgent
needs," he said.
data from compassionate access will create setbacks for drug development are
misplaced, according to Crowley. "To avoid granting requests, CEOs give
the excuse that they need to preserve integrity of studies and data, that if
they give [an experimental drug] to really sick people, it may not help them
and that would set back the whole program. I don't think that's the case;
companies are overly conservative," he said.
BioCentury FDA is "trying to clear up misperceptions on the part of
companies" that think providing an unapproved product to a very sick
patient might complicate the review and approval of the drug.
When is 'early'?
There is also
disagreement within industry about when access should be granted to
disagreed with provisions in RTT laws that allow access to compounds after
recognize that when people are desperately ill they are willing to take greater
risks," she said. "Until a drug has a positive efficacy signal in a
clinical trial, we really don't know if it might work, so I think that until
there is a positive signal, we need to restrict it to the clinical process."
King added: "If
the positive signal is so strong it is generally accepted the drug works, maybe
we need to make the drug available through some kind of accelerated approval."
he is a strong supporter of compassionate access, "but that doesn't mean
that as soon as you have an inkling of efficacy and safety anyone should have
access to the drug."
Reid, a venture partner at Alloy Ventures,
told BioCentury he supports the use of state RTT laws to provide access to
compounds after Phase I in some cases. States are "laboratories of
democracy," and "elected state governments should be free to experiment with the
provision of investigational drugs outside FDA oversight for patients with
terminal illnesses who have run out of options," he said.
learn whether these reforms have too many unintended consequences or are a path
for others to follow," Reid told BioCentury.
clearly is hoping to avoid instigating a legal challenge to state RTT laws, it
probably would win a case based on the preemption of federal drug regulation
over state laws, according to Kurt Karst, a director at Hyman, Phelps &
McNamara P.C., a firm specializing in FDA law. "If PhRMA or FDA were to
challenge [state RTT laws], they have good precedence behind them to prop up
their cases," he told BioCentury.
Karst added: "I
really wonder whether FDA or PhRMA would take on the challenge. It is easy to
put up a desperate patient who would die without [access to an experimental
drug] and here's big bad PhRMA or FDA suing to take it away from them."
Klasmeier, who leads the food, drug and medical device regulatory practice at
Sidley Austin LLP, agreed. "It would be very politically tough for the
government to stand in the way," she said.
added: "It reminds me of what is happening with marijuana where you have a
federal administrative architecture that gives states a lot of leeway to be
responsive to what's happening on the ground."
laws are a response to a "seismic shift" in social and political
attitudes toward the regulation of drugs and patient empowerment, according to
nothing is changing in FDA's or the industry's postures, but what is changing
is the tolerance of patients for a restrictive regulatory regime,"
according to Klasmeier. "It is not just changes in case law, but broader
atmospheric changes that make it obvious the regulatory and enforcement
environment has to change. Patients will not tolerate government getting in the
way of access to investigational drugs."
Companies and Institutions
Abigail Alliance, Lorton,
Amicus Therapeutics Inc.
(NASDAQ:FOLD), Cranbury, N.J.
Organization (BIO), Washington, D.C.
Chimerix Inc. (NASDAQ:CMRX),
Coalition Against Childhood
Cancer, Washington, D.C.
(NYSE-M:CUR), Rockville, Md.
(NASDAQ:GLYC), Gaithersburg, Md.
Max Cure Foundation, New
National Organization for Rare
Disorders (NORD), Danbury, Conn.
Patients for Stem Cells,
Pharmaceutical Research and
Manufacturers of America (PhRMA), Washington, D.C.
U.S. Food and Drug
Administration (FDA), Silver Spring, Md.