FDA Approves Mavyret (glecaprevir and pibrentasvir) as First Treatment for All Genotypes of Hepatitis C in Pediatric Patients

The U.S. Food and Drug Administration today approved Mavyret (telaprevir and pibrentasvir) tablets to treat all six genotypes of hepatitis C virus (HCV) in children ages 12 to 17. Mavyret was previously approved to treat HCV in adults in 2017.

   Pibrentasvir

                                  Glecaprevir

“Direct-acting antiviral drugs reduce the amount of HCV in the body by preventing the virus from multiplying, and in most cases, they cure HCV infection,” said Jeffrey Murray, M.D., M.P.H., deputy director of the Division of Antiviral Products in the FDA’s Center for Drug Evaluation and Research. “Today’s approval represents another treatment option for children and adolescents with HCV infection, but for the first time, in all genotypes of HCV.”

HCV is a viral disease that causes inflammation of the liver that can lead to diminished liver function or liver failure. According to the U.S. Centers for Disease Control and Prevention, an estimated 2.7 to 3.9 million people in the U.S. have chronic HCV, and children born to HCV-positive mothers are at risk for HCV infection. It is estimated that there are 23,000 to 46,000 children in the U.S. with HCV infection.

With today’s approval, dosing information is provided for Mavyret for the treatment of adult or pediatric patients 12 years and older, or weighing at least 99 pounds, who are infected with any of six identified HCV genotypes either without cirrhosis or with compensated cirrhosis.

The safety and efficacy of Mavyret in pediatric patients was evaluated during clinical trials of 47 patients with genotype 1, 2, 3 or 4 HCV infection without cirrhosis or with mild cirrhosis. Results of the trials demonstrated that 100 percent of patients who received Mavyret for eight or 16 weeks had no virus detected in the blood 12 weeks after finishing treatment, suggesting that patients’ infection had been cured. In pediatric patients with cirrhosis, history of a kidney and/or liver transplant, or genotype 5 or 6 HCV infection, the safety and efficacy of Mavyret are supported by previous studies observed in glecaprevir and pibrentasvir in adults. The adverse reactions observed were consistent with those observed in clinical studies of Mavyret in adults.

Treatment duration with Mavyret differs depending on treatment history, viral genotype and cirrhosis status. The most common adverse reactions in patients taking Mavyret were headache and fatigue. Mavyret is not recommended in patients with moderate cirrhosis and contraindicated in patients with severe cirrhosis. It is also contraindicated in patients taking the drugs atazanavir and rifampin.

Hepatitis B virus (HBV) reactivation has been reported in HCV/HBV coinfected adult patients who were undergoing or had completed treatment with HCV direct-acting antivirals, and who were not receiving HBV antiviral therapy. HBV reactivation in patients treated with direct-acting antiviral medicines can result in serious liver problems or death in some patients. Health care professionals should screen all patients for evidence of current or prior HBV infection before starting treatment with Mavyret.

https://www.drugbank.ca/drugs/DB13879

https://pubchem.ncbi.nlm.nih.gov/compound/Glecaprevir#section=Structures

https://en.wikipedia.org/wiki/Pibrentasvir

https://pubchem.ncbi.nlm.nih.gov/compound/Pibrentasvir

FDA Approves Mavyret (glecaprevir and pibrentasvir) as First Treatment for All Genotypes of Hepatitis C in Pediatric Patients

New molecule could become first treatment against chemotherapy-induced neuropathy

IDIBELL Researchers of the Neuro-Oncology Unit of Bellvitge University Hospital - Catalan Institute of Oncology, led by Dr. Jordi Bruna, have successfully tested a new molecule capable of preventing the development of peripheral neuropathy induced by chemotherapy in cancer patients, especially in colon cancer cases, the third most common neoplasm in the world. The molecule, which has a completely novel mechanism of action, would be the first treatment against this neurological complication, for which no effective treatment has yet been approved.

One of the main adverse effects of certain chemotherapeutics used in the treatment of cancers is peripheral neuropathy, which can cause tingling, numbness, pain or alterations in the functionality of patients, among others. This complication, so far, has been regarded as a "price to pay" despite having a demonstrated negative impact on the quality of life of the patient, increasing their care expenses and often preventing the complete and effective administration of the cytostatic treatment, with the potential decrease of survival chances that entails.

Researchers at the HUB-ICO-IDIBELL Unit identified a new molecule - developed by the Catalan laboratory Esteve - as a candidate to prevent  the onset of this adverse effect. "Through a public-private partnership, we have been able to design a Phase 2b clinical trial (randomized with placebo), which has allowed us to get a great deal of scientific information - effect on pain, pathophysiology - and draw conclusions as to the potential of the drug in the prevention of neuropathies during cytostatic treatment", explains Dr. Bruna, who led the trial.

The results of the study prove a decrease in the appearance of disorders associated with nerve dysfunction in those cancer patients who took the new drug. "When the trial was designed, safety data from the previous trials limited the duration of treatment with the new molecule and this meant that we had to work at low doses in relation to the duration of the chemotherapy treatment, but we have nevertheless obtained positive results and now we have enough information to be able to extend the duration of the treatment. Therefore, we hope to obtain even more satisfactory results" the IDIBELL researcher comments.

"Given the usual pace of clinical trials and drug agencies following fast-track approval processes in severe or orphan pathologies, this new drug could potentially reach the market soon, since it would be the first available treatment to avoid this type of neuropathy. In addition,  it has other medical uses as a non-opioid analgesic", adds Bruna. In any case, improving pain control and reducing the occurrence of severe neuropathy is undoubtedly the most prominent benefit of the development of this novel drug.