The two GLP-1 drugs are known for their properties to slow stomach emptying and cut food cravings. For Zydus, which was building its pipeline of innovative drugs, it was an audacious goal. Obesity drugs had not made the impact and too many large companies were deep in research for anti-diabetes drugs.
Besides, scientists across the world had laboured hard to pack the power of injectable biologics into an orally deliverable pill. That’s because peptides (short amino acid chains) are known to be fragile and degrade in the gastrointestinal tract leading to poor absorption and overall low efficacy. Undaunted though Zydus scientists knew they had a potential breakthrough the world may sit up and take note one day. In June 2010, Zydus (then Zydus Cadila) said in a statement it received permissions to conduct phase I clinical trials from the Drugs Controller General of India for ZYOG1.
Designed using a unique platform technology, the drug had demonstrated beneficial effects in preclinical models on glucose and HbA1c reduction and showed an added benefit of weight loss. It had a differentiated safety profile with no nausea-like symptoms in preclinical lab studies.
Zydus saw success with an oral GLP-1 drug in 2010, but shelved clinical development owing to costs
Pankaj Patel, chairman, Zydus had said the discovery of ZYOG1 was a significant achievement. “This novel molecule would address unmet medical needs in treating diabetes and holds promising potential in the anti-diabetic and anti-obesity market,” he added.
The drug had the right scientific backing. Among the key advisors for Zydus was Richard DiMarchi, who is known for his contributions in the research of GLP-1 drugs. To his credit, DiMarchi had an illustrious record as a distinguished professor at Indiana University. He had also worked for several years as a scientist at Eli Lilly.
Records show Zydus, however, shelved the clinical development of ZYOG1. “At that time, research in diabetes drugs involved significant global clinical development costs as the US FDA had laid out stringent safety regulations. Sustaining the costs was difficult and obesity was not even seen as a big unmet opportunity,” a veteran scientist told ET.”If we had progressed, ZYOG1 would have been a successful asset,” said a senior company official, adding, “Results in pre-clinical studies is too early to claim success,” the scientist added.
In the last few years, a slew of Chinese drug makers have out-licensed their experimental weight-loss drugs to US and European companies. Ironically, they were set up years after Zydus had hit its first success.
Novo Nordisk, the makers of Ozempic and Wegovy, that has a significant share of the global market for insulin and obesity treatments acknowledge the challenges in developing an oral GLP-1 drug. In the early 2000s, the company started work on oral delivery of biologic medicines. “We began exploring different routes of administration, initially focused on insulin and GLP-1. Through dedicated protein and peptide engineering efforts, we managed to create the first ever oral biologic of its kind-oral semaglutide for type 2 diabetes launched in 2019.”
The oral peptide drug is sold in India as Rybelsus. The same orally administered drug was approved in the US last month.
The first injectable GLP-1 agonist was approved by the US FDA in May 2005. Named Byetta (exenatide) from Amylin Pharma, it was prescribed to treat type 2 diabetes. It partnered with Eli Lilly to sell the drug.
Novo Nordisk’s incretin therapies Ozempic/Wegovy stand amongst the biggest breakthroughs in the history of the industry. Similarly, Mounjaro/Zepbound is fuelling Eli Lilly’s ascent as the most valued drug maker in the world. But other pharma giants are not giving up yet. Pfizer, for example, in September last year, acquired a three-year old drug maker Metsera for $10 billion outbidding Novo Nordisk in the chase.
Indian drug makers are steadily building their innovative drugs pipeline. Sun Pharma has utreglutide, a novel drug for obesity and metabolic disorders in early research. But ZYOG1 could have been the much-needed push to ambitions of Indian companies. As an exception, an Indian company could have been ahead of its Chinese peers.
