Developing a herbal-based drug for Hepatitis B

Dr Pralhad Patki

Today, a lot is being written about the potential of herbal medicine. Therapeutic benefits of herbs like turmeric, ginger and winter cherry (ashvagandha) are being researched across the world.

As a herbal healthcare company, Himalaya has been developing phytopharmaceutical formulations for the past 80 years. Herbal medicine, if backed by modern research, can become the first line of treatment for several conditions, and at other times, contribute to a holistic regimen that improves quality of life.

Enter: Liv.52

Himalaya’s flagship brand, Liv.52, developed in 1955, is the result of years of research. For many years, Himalaya’s scientists were working on a natural remedy to improve liver function. It was during the 1950’s that clinical trials were performed on several coded liver formulations, and one of them, coded 52, showed remarkable results in the treatment of hepatitis. This led to wider product testing and further investigation. Tests conducted across India with formula 52 showed significant improvement in liver function. The samples of formula 52 were in great demand from doctors who conducted the trials. Subsequently, the product was called Liv.52, the brand name to aid doctor recall.

Today, Liv.52 is backed by 250 clinical studies and is the only herbal drug with a meta-analysis study in infective hepatitis. It is registered in over 65 countries, including Russia where is prescribed as an adjuvant to counter the side-effects of anti-TB medication. In 2013, Liv.52 occupied the number seven position in a list of top bestselling drugs in India, as per the Indian Pharmaceutical Market (IPM) review.

Initially, Liv.52 was recommended for the treatment of jaundice. Over the years, Liv.52 has proven effective for the treatment of liver disorders including fatty liver and as an adjuvant to hepatotoxic drugs like statins, chemotherapeutic agents and antitubercular agents.

What about hepatitis B?

As makers of Liv.52, Himalaya had already carried out a lot of research on liver disease and herbs that work best for the treatment of liver conditions. Applying this knowledge to develop a drug for Hepatitis B was, therefore, a natural extension.

For this purpose, 120 plants were screened by the research team. Scientists were looking for a plant that exhibited hepato-protective activity as well as antiviral activity against the Hepatitis B virus. Among these, Nut Grass (Cyperusrotundus or Musta) and Umbrella’s Edge (Cyperus scariosus or Nagaramustaka) revealed potent antiviral properties.

The formulation, containing extracts of the two herbs, was first tested in vitro on hepatic cell lines. The infected cell lines, when treated with the extracts, multiplied without the virus. Results showed that the drug suppressed the replication of viral DNA involved in HBV, and eliminated the virus by reverse transcriptase inhibition. In fact, the formulation was successful in suppressing HBV surface antigens (HBsAg) in in vitro experiments.

The success of the in vitro experiments encouraged the scientists to move on to the next phase of preclinical evaluation – in vivo experiments (a recognised model for screening Hepatitis B virus in animals, recognised by WHO). Animals infected with Hepatitis B revealed that extracts of two plants were highly efficacious in treatment of this disease. These tests helped establish efficacy of the drug and arrive at a dosage. The experiments were repeated a number of times and produced encouraging results.

We then undertook preclinical toxicity studies including acute toxicity, sub-chronic and chronic toxicity studies to understand the effect of long-term administration of the drug on body organs, blood chemistry, hormones etc. We also conducted carcinogenic studies. Mutagenicity studies in bacteria, conducted as per WHO guidelines, revealed that the drug did not produce any adverse effects or mutations in future generations/ progeny.

After establishing the safety of the drug through in vitro and in vivo experiments, we moved on to human clinical trials after obtaining ethical clearance. Phase I of these trials conducted in 20 healthy individuals, established the safety of this drug. The studies showed that the drug did not produce any adverse effects even when given for longer duration.

In Phase II clinical trials, the drug was tested in a small sample of Hepatitis B patients who were not undergoing any other treatment. We conducted these tests in two hospitals in Bangalore and Baroda Govt. Medical College and Hospital, Baroda. These tests helped us establish the efficacy and safety of the drug in the prescribed dosage. Again, the results were encouraging. Patients taking the drug showed symptomatic relief, biochemical relief and sero conversion.

In Phase III clinical trials, we tested the drug on a substantial number of patients. This was a double blind placebo controlled randomised study. The trials were conducted in leading hospitals and institutes across India including Osmania Medical College Hospital, Hyderabad, Maulana Azad Medical College in Delhi, Government Medical College, Baroda, and Sanjay Gandhi Postgraduate Medical Institute, Lucknow among others. The tests revealed the beneficial effects of the formulation in clearance of HBs antigen in some patients. The results of these tests have been published in peer review and leading medical journals, including Antiviral Research.

Launched in 2011, Liv.52 HB has received an encouraging response. Available at the fraction of the price of available treatment of Hepatitis B, Liv.52 HB is affordable, efficacious and completely devoid of side effects.