New Delhi: A 73-year-old woman, suffering from bile duct cancer and in urgent need of liver transplant, had been hospitalised at the Texas Medical Centre in the US for over six weeks due to an acute infection that had been preventing her from undergoing the life-saving procedure.
Two deadly superbugs, klebsiella pneumoniae and pseudomonas aeruginosa, had triggered sepsis, liver abscess and cholangitis (inflammation in the bile duct) in the septuagenarian patient, and were not responding to any of the high-end antibiotics being tried on her.
This forced the medical team at the hospital to plead to the US Food and Drug Administration (USFDA) earlier this month for allowing the use of a novel antibiotic—Zaynich or WCK 5222—under its expanded access programme. Within days of use of the novel drug, the patient was cured of the infection.
Zaynich by Mumbai-based pharma company Wockhardt has created ripples with its astounding results against extremely drug resistant superbugs that do not respond to any other antibiotics.
The drug has now completed phase 3 clinical trials in nearly 400 patients, and the company is looking to file for regulatory approvals in India, US and other countries in 2025, Wockhardt officials told ThePrint.
In June, Zaynich had saved the life of a young patient with multiple infections and wounds, under treatment at Irvine School of Medicine in California after special permission from the USFDA to use the drug.
Under the USFDA’s expanded access programme, a patient is allowed access to an investigational drug for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available.
“The access was granted in case of the bile duct cancer patient, too, and within days of use of Zaynich, the patient was cured of the infection and ready to undergo the transplant. She is now recovering following the procedure,” Dr Mahesh Patel, director, drug discovery research, Wockhardt, told ThePrint.
Zaynich is a combination of cefepime, a generic antibiotic in use for decades, with zidebactam, a novel beta-lactam enhancer which is an inert compound that neutralises enzymes in bacteria which prevent the antibiotic from killing the pathogen.
Just last month, another antibiotic—Nafithromycin by Wockhardt—indicated for treatment of community-acquired bacterial pneumonia (CABP), developed in support from the Centre’s Department of Biotechnology, was also soft-launched in India.
Unlike Zaynich, Nafithromycin is meant for use in patients outside hospitals for treating lower respiratory tract infections which disproportionately affect vulnerable populations such as kids, the elderly and immunocompromised hosts such as patients with diabetes and cancers.
‘Nearly 100% efficacy’
Zaynich is indicated for use in hospitalised patients with conditions such as hospital-acquired pneumonia, bloodstream infections, intra-abdominal infections and complicated urinary tract infections (UTIs), among others.
Importantly, the medicine has been found to be highly effective against gram negative bacteria—the pathogens that are particularly difficult to treat and are a big challenge in the Indian context.
In India, one of the sites for phase 3 trials of the drug, a parallel trial of Zaynich has been going on to assess its efficacy against carbapenem-resistant pathogens in nearly 65 patients.
Additionally, the drug has also been used in over 30 critically ill patients on compassionate basis, so far.
These patients, to the surprise of their doctors, have all recovered from the life-threatening infections which were not responding even to carbepenem class of antibiotics.
Carbapenems are considered last resort antibiotics and for patients infected with pathogens resistant to these, there are barely any other options available.
“The drug has shown nearly 100 percent efficacy in the patients,” said Dr Sachin Bhagwat, clinical microbiologist and chief scientific officer at Wockhardt.
Officials attached with the company also said data related to late-stage clinical trials of Zaynich is now being analysed and they hope to get regulatory approval for the drug in India by mid-2025.
For a large number of clinicians struggling to save lives due to fatal infections in India’s intensive care units (ICUs), this is the biggest hope in years.
“This drug could be a game-changer for India’s fight against antimicrobial resistance (AMR). I don’t see any other antibiotic as powerful as Zaynich getting available to clinicians in at least five or even 10 years anywhere in the world,” Dr Balaji Veeraraghavan, head of microbiology at Christian Medical College, Vellore, told ThePrint.
Veeraraghvan is one of the investigators associated with the phase 3 clinical trials of the drug, which have been conducted in India, Europe and the US.
Findings of the Global Research on Antimicrobial Resistance (GRAM) Project, released in September, showed that between 3 and 10.4 lakh people died in India in 2019 due to bacterial antimicrobial resistance (AMR), a condition in which pathogenic bacteria no longer respond to antibiotics.
The report also said that 29.9 lakh people died in the country either directly from or due to conditions triggered by sepsis—blood poisoning in which the body has an extreme reaction to infection, and whose management has become difficult due to AMR.
In June, a molecule developed fully by Chennai-based Orchid Pharma, enmetazobactam, which had become the first-ever USFDA-approved “new drug” from India, was also launched in the country.
The combination of enmetazobactam—invented by scientists associated with Orchid Pharma in 2008—and cefipime is indicated in cases of moderate to severe bacterial infections such as complicated UTIs.
‘Targets gram-negative bacteria’
Wockhardt started working on Zaynich in 2007-2008, apart from several other antibiotic molecules, in line with company founder and chairman Habil F. Khorakiwala’s decision in the mid-1990s to focus his company’s drug discovery research efforts on the search for new antibiotics.
“He saw AMR as a massive public health challenge in the coming times, when no one anticipated it to be as big a problem as it has become today,” Bhagwat said.
The World Health Organisation (WHO) estimates that AMR was directly responsible for 1.27 million global deaths in 2019 and also contributed to 4.95 million deaths. Further, it is estimated that by 2050, AMR could be leading to 10 million deaths annually.
What is even more concerning is the fact there is a lack of new antibiotics in the pipeline to treat infections even as the problem of evolution of drug resistant bacteria due to selection and drug pressures persists.
In 2021, for instance, there were only 27 new antibiotics in clinical development against priority pathogens, down from 31 products in 2017, according to a WHO report.
Officials associated with Wockhardt explained that the significance of Zaynich lies in the fact that it is highly effective against several gram-negative bacteria highly prevalent in ICUs in Indian hospitals, such as drug-resistant K pneumoniae, Acinetobacter baumannii, and Escherichia coli.
Dr Subramanian Swaminathan, a senior infectious disease specialist with Gleneagles Global Hospital in Chennai, pointed out that India faces unique challenges on the AMR front, unlike the west, due to issues such as global warming and climate change.
“In the west, gram-positive bacteria are commoner and therefore developing antibiotics against gram-negative bacteria, which are more difficult to treat and more resistant to antibiotics, has not been on the priority list of big pharmaceutical companies,” he said.
Also, antibiotics are not a lucrative therapeutic area for many companies because they are typically used for shorter duration—unlike drugs for lifestyle diseases and cancer—and as such offer lesser opportunities for companies to make big money, underlined the doctor.
“The development of antibiotics such as Zaynich which is highly effective against drug-resistant bacteria in our hospitals is, therefore, going to be a game-changer as the problem of drug resistant gram-negative bacteria is no longer limited to tropical and sub-tropical countries,” said Swaminathan.
Limitation
Zaynich is also highly safe, apart from being very effective, said investigators attached with clinical trials of the drug, unlike some other last resort antibiotics such as colistin which can lead to side effects such as kidney and neurological issues in users.
The limitation of Zaynich, however, is that it will not be very effective in case of anaerobic and gram-positive bacteria, and fungal infections.
“However, in our experience, up to 90 percent of cases of hospital-acquired infection are due to gram-negative bacteria in Indian hospitals, and for them, this drug holds big promise,” said Swaminathan.
(Edited by Nida Fatima Siddiqui)