A federal law that was enacted in May creates a new mechanism for U.S. patients to obtain investigational drugs, but the extent to which people will be able to use this option is unclear.
The right-to-try legislation—officially known as the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017—was signed into law on May 30. The act is named for 3 Americans with amyotrophic lateral sclerosis (ALS) and 1 with Duchenne muscular dystrophy who reportedly lacked access to investigational drugs through FDA’s expanded access programs.
The new law amends the Federal Food, Drug, and Cosmetic Act to permit patients to obtain investigational drugs outside of clinical trials or expanded access programs. The law also shields physicians, dispensers, and drug companies from liability related to both the use of the drugs and the refusal to provide them.
To be eligible, patients must have a diagnosis of a life-threatening disease or condition and must have exhausted FDA-approved treatment options. Patients must also be unable to participate in a clinical trial involving the investigational drug. The medication must have cleared Phase I development and be under FDA review for marketing approval or under investigation in a clinical trial that is intended to support FDA approval or licensure.
“I think this legislation is something that sounded good but really isn’t going to do anything, unfortunately,” said Marjorie Phillips, clinical research pharmacist at Augusta University Health in Georgia.
Georgia passed a right-to-try law in 2016, with a July 2017 effective date. Phillips said she is unaware of any attempt by her organization’s physicians or patients to obtain investigational drugs under the state law.
An important obstacle to the success of the right-to-try law, she said, is that the drug companies that sponsor FDA-required investigational new drug (IND) applications have little incentive to make those drugs available to patients through the new pathway.
“I can’t see them being willing to do something that would take resources away from trying to get a potentially beneficial product to market,” Phillips said.
Chaim Lebovits, president and chief executive officer of Israel-headquartered BrainStorm Cell Therapeutics, acknowledged that concern during a June 7 conference call about right-to-try access for the company’s late-stage investigational cell therapy product for the treatment of ALS.
“Any company has ample reasons not to want to do anything outside the trial,” Lebovits said. “My fiduciary obligation is to make sure that the Phase III trial is not derailed by anything.”
Lebovits lent the company’s apparent support to the right-to-try law by appearing at the White House signing ceremony for the legislation.
Nevertheless, BrainStorm on June 26 announced that it would not make its ALS therapy available under the right-to-try law. The announcement described the expense of preparing the investigational product, which is derived from autologous bone marrow stem cells, as the primary barrier to using the new access pathway.
According to the company’s website, BrainStorm does not offer its investigational ALS therapy through FDA’s expanded access programs.
FDA Commissioner Scott Gottlieb said during testimony before a congressional committee last October that the agency receives over 1,000 applications annually for expanded access to investigational drugs and approves 99% of them. He said emergency access is usually authorized immediately over the phone, and nonemergency access is approved within a few days.
FDA’s individual patient expanded-access IND application process is the usual method for a treating physician to obtain an investigational drug for a patient outside of a clinical trial. The process requires the physician to submit a 2-page form to FDA that provides clinical information and describes the treatment plan, including the dose, route and schedule of administration, planned duration of treatment, monitoring procedures, and treatment modifications to be made in the event of toxicity. Applicants must also confirm that the manufacturer has authorized the use of the medication.
Treating physicians must obtain informed consent from the patient and approval from an overseeing institutional review board (IRB), which is charged with protecting the welfare and rights of clinical research participants.
Gottlieb noted during his testimony that FDA makes meaningful safety-related changes in the proposed treatment plan for about 10% of expanded access requests. Often, he said, the changes are based on confidential information from the NDA sponsor that is unavailable to the treating physician.
The right-to-try process bypasses both FDA’s safety review and IRB involvement.
Phillips, who chairs her hospital’s IRB, said the new law may be incompatible with established procedures at medical facilities.
“For example, our pharmacy and therapeutics committee has policies related to procuring medications,” she said. “They have to be FDA approved unless they’re accessed through an IRB-approved protocol under an FDA IND. So, we would actually have to change our policies and procedures to be able to take drugs through this [right-to-try] pathway.”
When considering such policy changes, she said, “I think we’d have a lot of concerns about whether it’s necessary or what value it adds.”
Phillips said “a fair number” of her organization’s patients have obtained investigational drugs through individual-patient IND protocols. Often, she said, the treating physicians have experience using those medications in clinical trials and are able to determine whether an investigational therapy is the patient’s best option.
She also praised the efforts of FDA staff members who handle inquiries about expanded access.
“They’ve really bent over backwards . . . to get the applications approved quickly,” Phillips said. “And there’s been really, really good cooperation between the physician, the FDA, and the manufacturer to make this happen when it needs to happen for a patient.”
Detailed information about expanded access programs, which are not supplanted by the right-to-try law, is available online from the nonprofit Reagan–Udall Foundation for the Food and Drug Administration.
A key question about the right-to-try law—who will pay for medications obtained through the new access pathway—remains largely unanswered.
The federal regulations that describe the process for IND sponsors to charge patients for investigational drugs require an IRB to authorize the proposed use of the drug and FDA to approve a plan to charge for the drug. Those regulations and a resultant 2016 guidance document from FDA refer specifically to the agency’s expanded access programs and don’t appear to fit the less regulated pathway created by the right-to-try law.
A spokesman from FDA’s trade press office stated in an email that an internal group “will be addressing these and other questions from patients, manufacturers and providers” as the agency evaluates how to implement and support the right-to-try law.
He stated that the agency will consider whether new guidance documents or other recommendations are necessary.
[This news story appears in the August 1, 2018, issue of AJHP.]