After almost a year of pilot testing, a New York University School of Medicine-led program to vet compassionate use requests for a Johnson & Johnson cancer drug offers lessons in how to equitably consider requests for pre-approval access to investigational drugs.

Among these learnings are the importance of having a company website that provides easy access to information about requesting compassionate use, an emphasis on anonymity in how requests are submitted and fairness in how they are judged, and a quick turnaround time for responses.

Janssen is assessing how to expand the collaboration with CompAC across its portfolio, CMO Ray said.

J&J's Janssen Pharmaceutical Cos. is considering whether to expand use of this approach, known as the Compassionate Use Advisory Committee (CompAC), across its pipeline. And although CompAC could become a model for other biopharma companies, it is not a one-size-fits-all approach and likely would require customization for a particular product or situation.

Objective, Independent, Informed Decision-Making

"Compassionate use" is among the various terms, including "expanded access," used to describe requests filed with a company on behalf of very sick or desperate patients who do not qualify for clinical trials but seek pre-approval access to an experimental drug.

Such requests can put biopharma companies between a rock and a hard place. Companies conducting clinical trials needed for marketing approval may have very limited supply of an investigational agent and be reluctant to divert the compound for use outside of the clinical trial setting.

However, manufacturers also face the risk of a backlash when compassionate use requests go unanswered or denied. Such outcomes can lead to negative headlines and public relations challenges, as was the case in 2014 with a compassionate use request for Chimerix Inc.'s experimental drug brincidofovir ([A#14140326003]).

Issues related to compassionate use – including the challenges that patients and providers face in navigating a process that involves companies, FDA and institutional review boards – have grown in prominence with the Chimerix case.

In early 2015, the agency unveiled a simplified form for physicians seeking compassionate use for a single patient ([A#14150204009]). On May 16, FDA and the Reagan-Udall Foundation will hold a public meeting on a proposal for an Expanded Access Navigator that would serve as a coordinated resource for information to help patients and health care providers.

A year ago, J&J partnered with NYU medical school to develop a new approach to vetting compassionate use requests. CompAC was launched in Spring 2015 as a pilot program to make recommendations on individual patient requests worldwide for Janssen's then-investigational multiple myeloma drug Darzalex (daratumumab).

The advisory committee grew out of a working group established at NYU medical school in response to challenges that biopharma companies faced in addressing requests for access to unapproved drugs, said Arthur Caplan, a professor and founding head of the Division of Bioethics at NYU's Langone Medical Center.

Caplan, who chairs the CompAC, talked about the committee's work during the recent World Orphan Drug Congress in Washington, DC, and in a subsequent interview with Pink Sheet. He said Janssen wanted to ensure that compassionate use requests received an independent review guided by ethical principles, "not just the individual gut feel of the person who happened to get the phone call" at the company.

In an interview, Janssen Chief Medical Officer Amrit Ray said compassionate use requests are among the most difficult decisions he faces.

In partnering with NYU medical school, "we were eager to put forward a way for those patients seeking compassionate use to have a process that was ethical, transparent and very patient-focused," Ray said.

The requests for compassionate use that Janssen receives are complex and often emotionally charged, Ray said. "There was a great need for a mechanism that allowed objective, independent and, importantly, well-informed decision-making to take place."

Leveling The Playing Field

CompAC is a 10-member panel comprising physicians, bioethicists, patients and patient advocates from five countries. J&J provides funding through the NYU medical school for the committee's operations, such as administrative expenses. However, the panel is independent from J&J.

The intent was to develop a consistent, transparent mechanism for allocating scarce drug quantity on a compassionate use basis for patients who didn't qualify for Janssen's clinical trials or expanded access programs for the multiple myeloma agent and who lacked other treatment options for the disease. Although CompAC was established with a specific compound in mind, there was an eye toward developing policies that could be applied more broadly across other companies and medical products.

"We wanted to even the playing field," Caplan said. "No more social media campaigns, no more PR experts trying to use the media, no more senators calling up the CMO or the CEO saying, 'Can you get me this drug?' That's not fair. What is fair is equality of opportunity."

Key to this was ensuring that anyone seeking compassionate use would be able to figure out how to do so through a company's website. "If we could get everybody into the website who wanted to find out about things, that was crucial because we want to have a fair playing field," Caplan said.

However, accomplishing this was challenging because patients and providers across the globe use different terminology for such pre-approval access.

"Janssen told us many, many times … that their website was very ready to go, very user friendly. So what we did was we found NYU students and said go in there and find information about drugs," Caplan said. "They couldn't do it. And we did it again, and again and again. It took a long time to get the website better."

Another equalizing factor was the decision to blind all requests for compassionate use. Identifying information, country of origin, gender and ethnicity were removed from the requests vetted by CompAC.

"We took all that out so that no one could lobby us," Caplan said. "Everybody would stand as equal before the committee. We standardized the information that was coming in on requests, making health care professionals try to fill out the same information as best we could so you didn't get a 50-page letter on behalf of one person and a paragraph on behalf of another."

Although the committee agreed to respond to compassionate use requests within a week, it also established an emergency response capability that could provide an answer within 24 hours. Voting rotates among CompAC's 10 members, with three individuals voting in any given week.

In the case of daratumumab, CompAC was dealing with a drug in late-stage development and under FDA review, but which was in very limited supply.

"This is a biologic – the capacity to make it was very limited and what they could make was going" to the registrational trials and expanded access program, Caplan said. "All we had was a small amount of drug to give out, and that was not sufficient to meet the requests of everybody who wanted it."

Consequently, the committee developed a set of principles that guided evaluation of requests (see box).

CompAC's Guiding Principles

Scientific likelihood of efficacious response
Avoiding harm
Functional status
Exhaustion of all existing approved treatments
Age
Support for dependents
Duration of disease
Prior participation in a clinical trial

Between July 1 and Dec. 31, Janssen received 160 pre-approval requests for daratumumab. Of these, 76 were deemed to be eligible to be considered for compassionate use. CompAC recommended granting 60 of the requests, and Janssen ultimately approved 62.

FDA granted accelerated approval to Darzalex as salvage treatment on Nov. 16, marking the drug's first approval anywhere in the world ([A#14151116006]). Although daratumumab is available in the US, CompAC continues to review compassionate use requests from outside the country.

Prospects For Expansion

Janssen viewed CompAC's first year as a proof-of-concept test, Ray said, and the company "now is actively assessing how we can expand the collaboration with CompAC across the Janssen portfolio."

This assessment includes consideration of whether changes would be needed if CompAC's scope were broadened. "We need to think about what would be the potential need of the CompAC," Ray said. "Would the composition stay the same? Would the current structure stay the same?"

Caplan sees the CompAC model as one that could be adopted by other biopharma companies, patient advocacy groups, trade associations and non-profits to handle requests for access to investigational drugs and devices, including in cases of public health emergencies such as pandemic flu and the Ebola and Zika viruses.

However, he cautioned that the CompAC model is "not a secret sauce."

"We did one drug with one company with one age cohort," Caplan said, noting also that daratumumab had a good safety and efficacy profile.

The CompAC model could prove more challenging and require adjustments if the compassionate use requests are for drugs earlier in clinical development, in very short supply, or for particularly vulnerable populations, such as pediatric patients, Caplan said.

He also acknowledged some challenges with this approach, including the fine line between ensuring that patients can find information about compassionate use on a company's website and the regulatory no-no of marketing an unapproved drug.

In addition, the financial costs with this type of approach – which Caplan estimated to be in the six figures for CompAC – are likely to be prohibitive for small companies. Consequently, this type of model may only be feasible for small companies through a consortium approach.

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However, there are some lessons from CompAC's first year that companies small and large can begin applying right now. For one thing, biopharma manufacturers could make compassionate use request information on their websites easier to find, Caplan said.

Both the Biotechnology Innovation Organization and the Pharmaceutical Research and Manufacturers of America have principles for their member companies on making information about compassionate use and expanded access readily available (see sidebar).

In addition, companies could anonymize and standardize compassionate use requests without going the extra step of creating an advisory committee to vet them, Caplan said.

"In some ways this drug doesn't capture everything, but I think it's been a good lesson about improving upon compassionate use access," he said. The pilot provides lessons for manufacturers of vaccines, devices and drugs "about a way to try to respond in a more coherent, fair and transparent manner."

[Editor's note: This story was updated May 9, 2016 to clarify that CompAC is run by NYU School of Medicine, not NYU.]

J&J's Compassionate Use Advisory Cmte. May Become Industry Model

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