Better treatment for rare diseases needed via compassionate use

Review of program since 1990s finds more benefits with early access than risks

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Most people with rare diseases given an experimental therapy through compassionate use programs show clinical benefits, and most of these treatments ultimately end up getting approved, according to a review study.

Based on these findings, the researchers argued that such programs — allowing certain patients with limited options access to treatments not yet approved — should be expanded to help people worldwide with rare disorders.

“We believe that a more efficient global [compassionate use] system should be in place to offer patients faster and more flexible access to innovative and novel investigational drugs,” the scientists wrote in the study “Efficacy and safety of compassionate use for rare diseases: a scoping review from 1991 to 2022,” published in the Orphanet Journal of Rare Diseases.

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First introduced in the U.S. in the late 1990s, compassionate use programs allow people with life-threatening conditions and without effective treatment options access to experimental therapies in clinical testing before they are approved for use by regulatory agencies.

In the U.S., these programs — also called expanded access by the U.S. Food and Drug Administration — can involve a single patient with an emergency, tens to hundreds of patients, or larger numbers after a therapy has shown promise in a late-stage trial, but it is not yet approved.

“Characterized by small and highly [variable] patient populations, there are limited or no approved treatments for many rare diseases, so patients may not have access to clinical trials,” the researchers wrote. “In such cases, compassionate use (CU) provides a potential way with patients to access unapproved investigational drugs before formal product approval.”

Compassionate use was seen to have an important part in treating AADC deficiency, an ultra-rare genetic condition.

For instance, compassionate use programs in Europe and Taiwan allowed children with AADC deficiency to access the gene therapy Upstaza (eladocagene exuparvovec) prior to its 2022 approval in the European Union and the U.K.

Data from these programs, showing the therapy’s ability to safely and effectively improve motor and nonmotor function in young children and those older than age 10, were part of the data package that supported Upstaza’s approval.

Scientists in China systematically reviewed studies published from January 1991 to December 2022 reporting cases of rare disease patients treated under compassionate use.

The goal was to “investigate the characteristics of compassionate use in the context of rare diseases, evaluate the efficacy and safety of compassionate use for rare diseases, and analyze the marketing approval of investigational drugs,” the researchers wrote.

A total of 46 studies, covering 2,079 patients and 39 treatment candidates, were included in the analysis. Most were done in the U.S. and Europe, and half targeted rare cancers, but other rare diseases also were included.

Clinical benefits seen in 83% of patients treated through compassionate use

In most cases (84.8%), results showed that treatments given through compassionate use programs led to clinical benefits for patients, easing symptoms in 35 reports (76.1%) and being curative in another four (8.7%).

Treatment side effects were reported for patients in about two-thirds of the studies. Across the studies, 136 patients died, and 19 of these deaths were deemed related to treatment.

“The safety of drugs for compassionate use cannot be fully evaluated due to the safety data were not covered in some enrolled studies,” the team wrote, adding that “the establishment of an adverse event reporting system specific to compassionate use is warranted.”

By Jan. 31, the study’s close of data collection, drugs tested in 33 of the 46 studies (71.7%) were approved for use in the country of the compassionate use program. On average, these programs were started a median of about two years before therapy approval.

About one-third of the therapies (36.9%) “received marketing approval within 5 years of the CU being in place,” the researchers wrote.

Given that “there hasn’t been much review studies on CU for RDs [rare diseases], this study fills in some of the gaps and provides valuable insights into the effectiveness and safety” of the program in these diseases, which can be used “for developing future drug policies,” the team wrote.

“In short, the efficient treatment of rare diseases remains a lot of challenge, and some regions have not established compassionate use programs,” they added.

Researchers also noted an “urgent need” to shorten the time between compassionate use and therapy approval and marketing “to expedite patients’ access to these drugs,” they wrote. They called for a global system to more efficiently offer rare disease patients access to such investigative therapies.

Besides efforts to expand access to these programs, the researchers also called for the creation of an open-access database to track safety and efficacy findings related to these programs, which could help with future research.