SALT LAKE CITY – Clinical whole-genome sequencing has provided molecular diagnoses for many rare disease patients already, but the test has been largely confined to high-income countries like the US and European nations.
Even within those countries, though, clinical WGS has been out of reach for patients without the means to pay for it or insurance to cover the test. To make testing more widely available to underserved children with rare, undiagnosed diseases and their families, Illumina and a number of clinical collaborators in 2016 launched a philanthropic clinical program called iHope. Under the program, Illumina is providing WGS testing free of charge through its clinical services laboratory in San Diego.
Seven years later, the program has expanded to clinical sites around the world, including in several low- and middle-income countries (LMIC), and has provided clinical WGS for hundreds of patients. At the American College of Medical Genetics and Genomics annual meeting here on Thursday, Ryan Taft, VP of scientific research at Illumina, presented results for 1,004 patients including how WGS affected their clinical care and what differences existed between those in high-income countries and in LMIC.
Patients were referred to the program by 24 clinical sites in eight countries, four classified as high-income (the US, Italy, United Arab Emirates, and New Zealand) and four considered LMIC (Democratic Republic of Congo, Ghana, Mexico, and Peru). Regardless of country, participants had to have no access to comprehensive molecular testing, be suspected of having a genetic disorder, and have no diagnosis.
Following the return of test reports, the investigators sent a survey to the ordering clinicians asking them about how the results changed their diagnostic thinking or the care of their patients, which was returned for 69 percent of participants.
Overall, about two-thirds of patients came from high-income countries and a third from LMIC clinics, and more than half were of non-European ancestry, Taft said. While the overall diagnostic rate was 41 percent, it was much higher at LMIC sites — 57 percent — than at high-income sites, where it was 34 percent. The likely reason for this, he said, is that in poorer countries, WGS was the first molecular test patients received, whereas in high-income countries, patients had already undergone other types of molecular testing and WGS was the "test of last resort."
The test results led to a change in management for 41 percent of patients when those changes included specialty referrals, imaging, lab tests, and therapeutic treatments. Changes in management were more frequent in LMIC (48 percent) than at high-income sites (36 percent). They rose to almost 70 percent when genetic counseling and avoided further testing was also counted. Also, patients who received a molecular diagnosis through WGS were almost six times more likely to have their management changed than those who did not.
Of note, even patients in LMIC were able to obtain appropriate therapies as a result of their molecular diagnosis, including one who received gene therapy and another who had a stem cell transplant, which Taft said some had doubted would happen when the program started because of those countries' healthcare systems. "Some assumptions about LMIC were clearly incorrect," he said.
One patient in Peru, for example, was diagnosed with dopa-responsive dystonia, and both she and her father responded well to subsequent treatment with levodopa.
Illumina and the nonprofit Genetic Alliance are in the process of expanding the program even further, Taft said, through the iHope Genetic Health program. Launched in late 2021, that program is funded by Illumina with $120 million in in-kind contributions over five years.
The goal is to fund or establish partner laboratories in other countries that will deliver clinical WGS pro bono to tens of thousands of patients per year. LunaPBC will provide a patient-centric data platform for the project, Taft said.
Illumina is currently looking for partner laboratories for the program, which it plans to expand over the next several years, he added.