Dr Murtaza Khorakiwala, MD, Wockhardt, shares the challenges faced with regards to AMR and his vision to create a continual stream of novel antibacterial therapies in a conversation with Mansha Gagneja
Why is antimicrobial resistance a global concern?
Today, global mortality due to anti-microbial resistance (AMR) is more than seven lakhs, which is slated to increase up to 10 million by 2050. Due to AMR, the additional healthcare cost per year is more than $4 billion globally. Moreover, there has been collateral damage to healthcare settings across the globe, with compromised ability to manage various surgeries, organ transplants, deliveries etc.
AMR through various multi-drug resistant superbugs as Enterobacteriaceae, Acinetobacter, ESBLs, Salmonella, Pseudomonas, Staphylococcus and Streptococcus, is leading to loss of lives at a great extent due to the uncontrolled deadly infections. Thus putting the entire healthcare industry under threat.
Why is research for new tools to combat drug resistance declining?
The research on new antibacterial agents is declining due to its economic unattractiveness. Antibiotics which are prescribed for shorter courses of one or two weeks do not generate sufficient return on investments to recoup the cost of research. Therefore, big pharma companies have vacated the field to focus on more lucrative lifestyle diseases requiring long-term therapies. This is paradoxical since majority of such therapies do not cure the disease but it helps companies earn good profits. On the other hand, antibiotics which actually cure the disease are priced much lower. In order to preserve the effectiveness of antibiotics used in critical care, they are required to be used judiciously for several years, thereby further curtailing their sales growth. This is unlikely for lifestyle disease products as their sales keep expanding on yearly basis. As a result of Big Pharma exodus from antibiotic discovery, internationally the skill sets required for antibiotic discovery have also sharply declined. On the other hand, scientific challenges involved in discovering novel antibiotics targeted towards multi-drug resistant pathogens have multiplied in view of a superbugs’ ability to deploy multiple resistance mechanisms. Such a scenario demands discovery of new agents that can tackle a broad range of pathogens and resistance mechanisms. This requires highly specialised skill sets and considerable insights in this therapeutic area, which is developed through long- term commitment. Looking at such challenges it is no wonder that in the past four to five years several Indian companies that were engaged in this field have also given up discovery efforts.
What are the challenges faced in formulation of antibiotics and anti-parasitic drugs?
As antibiotics have a wide range of uses besides treating infections, including pre and post-surgical propylaxis for a range of surgical procedures, organ transplant, and hip/ knee/ joint replacement, it is important that the formulations developed are compatible with a wide range of clinical conditions. Development of injectable formulations throws up a significant challenge in managing injection site tolerability. Similarly, oral formulations need to have good GI tolerability and rapid absorption for quick onset of antibacterial action.
How much share is allotted to research for AMR in Wockhardt?
Wockhardt has been engaged in drug discovery research for the last 20 years and invested significantly during this period. Last year, our spend on R&D itself was approximately 15 per cent of our sales of which our drug discovery portfolio is a critical component.
Wockhardt has recently received an approval for phase III clinical trial from the US FDA, could you brief us about the new superdrug?
WCK 5222 is a novel class of superdrug that introduces the first entirely new class of Gram-negative antibiotic treatment in 35 years. WCK5222 is expected to be a life-saving destination therapy for serious hospital acquired infections (HAIs) such as hospital acquired bacterial pneumonia, ventilator associated pneumonia and blood stream pneumonia and blood stream infections.
It would be the first antibiotic moving ahead in Phase III for five gram negative superbugs – Enterobacteriaceae, Acinetobacter, ESBLs, Salmonella, Pseudomonas.
Wockhardt has five drugs which have entered phase II and phase III clinical trials. What is the progress on these drugs?
Our NCEs WCK 771, WCK 2349 and WCK 4873, are against multi-drug resistant gram positive infections, while WCK 4282 and WCK 5222 are against multi-drug resistant gram negative infections.
In addition to WCK5222, WCK 771 and WCK 2349 drugs have received QIDP status.
Presently, this combination is entering phase III clinical trials in India, post successful completion of its global phase I and India-based phase II trials. It would cater to Indian and emerging markets.
Further, WCK 4873 is positioned against multi-drug resistant gram positive superbug and has successfully completed its global phase I trials and would be entering global phase II trials.
WCK 4282 is a combination product, effective for gram negative infections untreatable with current main therapies. It would be the first line antibiotic for hospital pathogens, addressing resistant cases due to multi-drug resistant superbugs. It is soon to enter global phase III trials.
Which are the other drugs in the pipeline?
Wockhardt intends to acquire global leadership in the field of antibiotics. We are focussed on creating a continual stream of well differentiated, novel antibacterial therapies and thus continuously easing the global AMR burden. Other drugs under development are targeting much needed therapeutic options for paediatric, diabetic foot infection patients.