Faldaprevir – An Effective Second-Wave Protease Inhibitor

 

Trek Therapeutics pic
Trek Therapeutics
Image: trektx.com

Robert Hindes, MD, co-founded Trek Therapeutics, which is organized as a public benefit corporation that seeks ways of developing innovative yet affordable and accessible antiviral medications. As chief medical officer, Robert Hindes, MD, is engaged with his team in Phase 2a studies of TD-6450 plus faldaprevir.

Faldaprevir, a second generation protease inhibitor, was initially developed for use with ribavirin and pegylated interferon, and it is currently used in new regimens that are interferon-free. In phase 2b and 3 studies in patients with previously untreated genotype 1b hepatitis C virus (HCV), faldaprevir combined with pegylated interferon and ribavirin resulted in SVR rate of 82%.

A 2015 paper published in Liver International evaluated the Phase 2b SOUND-C2 interferon-free study involving a combination of faldaprevir, ribavirin, and deleobuvir. The combination resulted in overall SVR rate of 92%, and was well-tolerated among patients with HCV genotype-1a and 1b. Along with simeprevir, faldaprevir is considered one of the most effective second generation protease inhibitors.

Trek Therapeutics Starts New TD-6450 Plus Faldaprevir Phase 2 Study

 

Trek Therapeutics pic
Trek Therapeutics
Image: trektx.com

As chief medical officer of Trek Therapeutics, a public benefit corporation, Robert Hindes, MD, heads a clinical team focused on developing affordable antiviral drugs for global markets. In June 2016, Robert Hindes, MD, and his company announced the start of a Phase 2a study of TD-6450 plus faldaprevir, with and without ribavirin, involving patients with genotype 1b (GT 1b) HCV infection at sites in the United States and New Zealand.

The new study follows the analysis of interim results for the same set of drugs being used to treat patients with HCV GT 4. The 16-patient study yielded successful results, with HCV RNA <LLOQ in all patients by Week 3 of treatment, and SVR in all 10 patients who have post-dosing results.

TD-6450 has been designed to provide better antiviral activity results with genotype 1 resistance-associated variants that are resistant to previously developed NS5A inhibitors, such as daclatasvir. Faldaprevir is a protease inhibitor that is highly active against HCV GT 1 and 4.

Gilead Sciences Awaits FDA Decision on Sofosbuvir/Velpatasvir for HCV

Gilead Sciences pic
Gilead Sciences
Image: gilead.com

As vice president of clinical development for Pharmasset, Robert Hindes, MD, played an important role in the development of sofosbuvir, known now as Sovaldi. When the small company was acquired by Gilead Sciences, the nucleoside polymerase inhibitor that Robert Hindes, MD, evaluated in combination with other drugs, continued to be evaluated in clinical trials conducted by Gilead.

In early 2016, the FDA granted priority status to a new drug application (NDA) from Gilead Sciences. This new drug is sofosbuvir/velpatasvir, a combination of a polymerase inhibitor and a next generation NS5A inhibitor. If approved, the fixed-dose combination is expected to be active against all HCV genotypes.

Placebo-controlled trials demonstrated the pan-genotypic activity of the drug, and it expected to be a more effective alternative to Harvoni in patients with non-GT1 HCV. Another recent trial showed 95 percent SVR for patients who have both HCV and HIV.

Sofosbuvir/velpatasvir received the designation of breakthrough therapy from the FDA, meaning the agency recognizes its potential for widespread use and major advances in the treatment of hepatitis C.

Gilead Sciences Acquired Pharmasset to Continue Work with HCV Cures

Gilead Sciences pic
Gilead Sciences
Image: gilead.com

During his time with Pharmasset, Robert Hindes, MD, helped to develop the HCV drug Sovaldi and led the company’s clinical development program. When the company was purchased by Gilead Sciences, Robert Hindes, MD, temporarily joined the Gilead team in a transitional capacity before leaving to cofound his own company.

In late 2011, pharmaceutical company Gilead Sciences announced an agreement to purchase the smaller company Pharmasset for $137 per share, or roughly $11 billion in total. This represented nearly a third of Gilead’s total value at the time, making the purchase both risky and rather remarkable. Pharmasset, which had less than 100 employees at the time of purchase, was a small research-based company that was making significant progress with two different drugs meant to treat chronic hepatitis C (HCV).

Gilead Sciences and Pharmasset representatives agreed that the companies shared a common vision for the development of HCV treatments. At the time, Gilead was making progress with its own HCV treatments, but determined that acquiring the Pharmasset nucleoside polymerase inhibitors would help it compete on a higher level and bring effective therapies to the public even faster.