Generic Direct-Acting Antivirals Effective in Hep C

Damian McNamara

May 02, 2017

AMSTERDAM — Almost all patients with hepatitis C who took legally imported generic versions of direct-acting antiviral agents achieved a sustained virologic response at 4 weeks, according to a new study.

"Treatment with generics works," said investigator James Freeman, MD, from the University of Tasmania in Hobart, Australia.

As it stands now, "unless doctors start being more proactive, you can foresee a time when, on the basis of current trends, medications are priced out of reach for all but the super rich," he said.

To look for a solution to that problem, Dr Freeman and his colleagues initiated the REDEMPTION studies (NCT02657694) to assess the effectiveness of generic versions of sofosbuvir, ledipasvir, daclatasvir, and velpatasvir from suppliers in Bangladesh, China, Egypt, and India.

Dr Freeman presented updated results on a cohort of 1087 patients from REDMPTION-1 here at the International Liver Congress 2017. He presented early results on 448 patients at last year's meeting.

His team examined outcomes in patients with hepatitis C from 42 countries who participated in one of four treatment-access programs, located in Australia, Russia, and Southeast Asia, which used imported, and therefore cheaper, direct-acting antivirals.

Mean age of the study participants was 44 years, 60% were male, 56% were infected with genotype 1 hepatitis C, mean baseline viral RNA load was 6.9 log IU/mL, and median length of treatment was 12 weeks.

Data are not yet available for all 1087 patients, but Dr Freeman reported that a sustained virologic response at week 4 was achieved by 94% of 523 patients and at week 12 was achieved by 89% of 450 patients. In addition, a viral RNA load below 25 IU/mL was achieved by 98% of 642 patients at the end of treatment.

Table: Achievement of a Viral RNA Load Below 25 IU/mL

    With or Without Ribavirin
Virologic Response Sofosbuvir Plus Ribavirin, % Sofosbuvir Plus Ledipasvir, % Sofosbuvir Plus Daclatasvir, %
Rapid 90 83 84
Sustained at 4 weeks 100 94 99
Sustained at 12 weeks 91 92 86
End of treatment 98 98 99


No new or unexpected adverse effects were reported. One patient experienced a reactivation of hepatitis B, three developed decompensated and then recompensated cirrhosis, and four developed hepatocellular carcinoma during or after treatment.

"We fully expected drop-off by SVR12," Dr Freeman explained. "But SVR12 has proven to be durable through SVR24 and SVR52."

An incomplete response at 4 weeks was associated with relapse, the investigators found.

Four-Week Response Crucial

Detectable virus at week 4, suggesting an incomplete response, was more common in the subgroup of patients who relapsed than in the cohort as a whole (44% vs 22%; odds ratio, 1.91; P = .02).

This means that patients with detectable virus at 4 weeks are in trouble because they have twice the chance of failing therapy, Dr Freeman said.

Being able to identify these patients "at a time when we can do something about it" is important, he explained. "We can then intensify treatment. It is more cost-effective to piggyback on top of the planned treatment than to add a new one."

These are not data points. These are the hopes, dreams, and lives of real people.

"These safety and efficacy results are not different than in any real-world cohort with approved drugs," said Xavier Forns, MD, from Hospital Clinic Barcelona in Spain.

"If quality controls are in place, I think there is no doubt that generic direct-acting antivirals will help cure patients in areas where currently approved combinations are not available or are restricted," he told Medscape Medical News.

The bioequivalence of generic and brand-name direct-acting antivirals has been demonstrated in previous studies, such as one recently conducted in Egypt (Int J Gen Med. 2017;10:1-6). However, access remains a major barrier. Generic direct-acting antivirals are not expected to be available in the United States until 2032, Dr Freeman noted.

"In a breakthrough that rivals the invention of penicillin, drugs that cure hepatitis C have reached the market, yet every 45 seconds, another patient dies from hepatitis C," said Dr Freeman. "These are not data points. These are the hopes, dreams, and lives of real people."

"We could treat 68 million people with hepatitis C and spend the same amount as we spend to treat one person with HIV for 1 year," he pointed out.

Dr Freeman and Dr Forns have disclosed no relevant financial relationships.

International Liver Congress (ILC) 2017: Abstract PS-097. Presented April 21, 2017.


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