Indian drugmakers to launch new products to counter superbugs

MADURAI, India — Pharmaceutical companies in India are introducing new drugs to treat the growing problem of antimicrobial resistance (AMR), which is one of the top threats to global public health.

AMR occurs when bugs grow stronger than the drugs meant to treat them. According to the World Health Organization, AMR was directly responsible for 1.27 million deaths worldwide in 2019 and contributed to 4.95 million more. The WHO says misuse and overuse of antibiotics in humans, plants and animals have led to the development of drug-resistant pathogens. Studies suggest there could be 40 million deaths by 2050 as a result of antibiotics losing efficacy, with those over age 70 the most vulnerable.

“India, with its long history of misuse of antibiotics, is at the epicenter of this AMR crisis — a breeding ground for dangerous superbugs,” said Balaji Veeraraghavan, a senior professor of microbiology at Christian Medical College and Hospital at Vellore in Southern India. “Drugs launched in the West to fight antimicrobial resistance don’t work against the drug-resistant, gram-negative bacterial infections we’re seeing in India,” he added.

This has driven the search for indigenous medicines that could work around the world.

Wockhardt, a Bombay Stock Exchange-listed drugmaker in Mumbai, on Thursday announced regulatory approval of a drug developed with support from the government-owned Biotechnology Industry Research Assistance Council. The drug, marketed as Miqnaf, targets community-acquired bacterial pneumonia, the kind that people have contracted outside hospitals or other health care facilities.

Wockhardt is developing another drug, Zaynich, which is undergoing Phase 3 clinical trials globally. It combines a new molecule, Zidebactam, with an existing antibiotic, Cefepime. The company expects to receive approval from the U.S. Food and Drug Administration for the medication sometime this year.

“The combination drug Zaynich (Zidebactam and Cefepime) shows promise against multidrug resistant bacteria, specifically, against two notorious pathogens: Pseudomonas aeruginosa and Acinetobacter baumanni,” said Ragothaman M Yennamalli, senior assistant professor at the Department of Bioinformatics at SASTRA University in the southern Indian state of Tamil Nadu.

About 1.3 million people died in 2019 globally due to antimicrobial resistance, according to the World Health Organization.   © Getty Images

In clinical trials, the drug was particularly effective in 30 patients in India, to whom it was administered on a compassionate basis when other antibiotics did not work, according to Veeraraghavan, whose hospital, Christian Medical College and Hospital, is participating in the bridging study. “Thousands of lives can be saved with the drug, especially over the next five to seven years,” he said.

In February last year, Enmetazobactam developed by Orchid Pharma, another listed company based in Chennai, became the first antimicrobial made in India to receive FDA approval. It is an injectable drug that treats severe infections like urinary tract infections, pneumonia, and bloodstream infections.

“It has a big role as a carbapenem-sparing agent,” said Abdul Ghafur, an infectious diseases specialist in Chennai. He is the primary author and coordinator of the “Chennai Declaration,” an initiative to tackle the challenge of antimicrobial resistance from an Indian perspective. Enmetazobactam gives doctors an alternative to carbapenems, so that they can avoid the overuse of these important last-resort drugs, he says. “It’s a molecule that will be extensively used in the future at a global level.”

Since 2012, doctors across India have seen a disturbing rise in carbapenem resistance — carbapenems are the last line of powerful antibiotics that can be used to treat bacterial infections, especially those caused by gram-negative bacteria. The most common carbapenem-resistant bacteria in India are E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa — germs that cause several types of infections, ranging from diarrhea, urinary tract infections and pneumonia, to sepsis or blood poisoning.

Developing a brand-new antibiotic can be extremely complex. “Currently, India is known for its cheap, generic drug manufacturing. But with the launch of these drugs, that perception can shift,” said Yennamalli of SASTRA University. “The focus will now be on innovative drug production.”

The U.S.-based biopharmaceutical company Bugworks Research, which was co-founded by an Indian serial entrepreneur, has a laboratory in Bengaluru. The company entered an agreement with the Global Antibiotic Research and Development Partnership, a nonprofit organization in Switzerland that develops new antibiotic treatments for drug-resistant bacterial infections. Bugworks is developing a new antibiotic, BWC0977, which industry sources say will take five to seven years to hit the market. The University of Tokyo Edge Capital Partners, one of Japan’s leading deep tech venture capital specialists, is among Bugworks’ investors.

However, “Sustainable patterns of antibiotic use must accompany the introduction of new drugs,” said Yennamalli of SASTRA University. Resistance to new antimicrobials can become widespread within just a few years, he pointed out.

India has a long history of misuse of antibiotics. Such misuse can lead to the rise of antimicrobial-resistant bacteria.

Wockhardt disclosed in its latest annual report that it had invested $500 million over 25 years in the development of Zaynich and other drugs. Treatment costs are estimated at $18,863 for a seven- to 10-day course of Zaynich, indicating significant market potential. Industry sources say the drug, a wide-spectrum antibiotic, can be used globally and has a potential market of $25 billion.

“I believe the Drugs Controller General of India must include strict clauses to ensure the controlled use of Cefepime-Zidebactam, as it is highly active against carbapenem-resistant bacteria. This molecule needs to be protected, rather than extensively marketed,” said Ghafur, the infectious diseases specialist. “The $25 billion market prediction makes me worried about the high probability of uncontrolled marketing.”

The price of the antibiotic in India is expected to be one-tenth of its global price. However, even that would be high by Indian standards. The high price could automatically limit its use, said Veeraraghavan of Christian Medical College and Hospital.

In addition to antibiotics developed in India, new agreements are now in place to widen access to antibiotics across Asia through sharing of technology and local manufacturing.

Orchid Pharma joined hands with Japanese drugmaker Shionogi to manufacture and distribute the latter’s antimicrobial drug Cefiderocol. It was approved by the FDA in 2019 and the European Medicines Agency in 2020, and is on the WHO Model List of Essential Medicines. And yet, previously, it was not affordable or available in the countries that needed it most.

Superbugs are an incredible challenge, and no single solution will be sufficient to contain them, said Yennamalli. “Continuous monitoring and development of new antibiotics and combination therapies are essential to keep up with their evolving threat,” he said. “The priority remains, however, to not let them develop in the first place.”

source : asia.nikkei