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Ledipasvir is a drug for the treatment of hepatitis C that was developed by Gilead Sciences.[1] After completing Phase III clinical trials, on February 10, 2014, Gilead filed for U.S. approval of a ledipasvir/sofosbuvir fixed-dose combination tablet for genotype 1 hepatitis C.[2][3] The ledipasvir/sofosbuvir combination is a direct-acting antiviral agent that interferes with HCV replication and can be used to treat patients with genotypes 1a or 1b without PEG-interferon or ribavirin.
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| Clinical data | |
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| Trade names | Harvoni (combination with sofosbuvir) |
| Other names | GS-5885 |
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| Routes of administration | By mouth |
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| Pharmacokinetic data | |
| Bioavailability | 76% |
| Protein binding | >99% |
| Metabolism | No cytochrome metabolism |
| Elimination half-life | 47 hrs |
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| Chemical and physical data | |
| Formula | C49H54F2N8O6 |
| Molar mass | 889.018 g·mol−1 |
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Ledipasvir is an inhibitor of NS5A, a hepatitis C virus protein.[citation needed]
Data presented at the 20th Conference on Retroviruses and Opportunistic Infections in March 2013 showed that a triple regimen of the nucleotide analog inhibitor sofosbuvir, ledipasvir, and ribavirin produced a 12-week post-treatment sustained virological response (SVR12) rate of 100% for both treatment-naive patients and prior non-responders with HCV genotype 1.[4][5] The sofosbuvir/ledipasvir coformulation is being tested with and without ribavirin. In February 2014 Gilead filed for United States Food and Drug Administration (FDA) approval of ledipasvir/sofosbuvir oral treatment, without interferon and ribavirin.[6]
On 10 October 2014 the FDA approved the combination product ledipasvir/sofosbuvir called Harvoni.[7]
Ledipasvir is most commonly used in combination with sofosbuvir for treatment in chronic hepatitis C genotype 1 patients. This drug has been tested and shown efficacy in treatment-naive and treatment experienced patients.[8]
According to clinical trials, ledipasvir/sofosbuvir has been very well tolerated with the most common side effects being fatigue and headache.[9]
Most drug-drug interactions with Harvoni involve Pgp-inducers such as St. John’s wort or rifampicin. Concomitant use will decrease the blood concentration of Harvoni and thus, have reduced therapeutic effects.[9]
Ledipasvir inhibits an important viral phosphoprotein, NS5A, which is involved in viral replication, assembly, and secretion.[10]
Sofosbuvir, on the other hand, is metabolized to a uridine triphosphate mimic, which acts as a RNA chain terminator when incorporated into RNA by NS5B polymerase.[10]
Similar to sofosbuvir, the cost of Harvoni has been a controversial topic. It costs $1,125 per pill in the US, translating to $63,000 for an 8-week treatment course, $94,500 for a 12-week treatment course, or $189,000 for a 24-week treatment course. Gilead justifies the cost by outweighing the benefit of curing hepatitis C over the cost of spending double on liver transplants or temporarily treating liver diseases. Gilead has provided a ledipasvir/sofosbuvir assistance program for eligible underserved or underinsured hepatitis C patients who cannot afford the costs of treatment.[10]
In July 2015 Gilead modified the eligibility criteria to receive Support Path benefits for HCV patients in the United States.[citation needed]
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