Pfizer stops working on oral GLP-1 obesity drugs after safety signal surface in clinical trials
Pfizer is catching up in the crowded obesity drug field, but hopes to compete with the daily drugs currently available with injectable GLP-1 products. Instead, Pfizer is stopping the development of its drug Danuglipron after liver complications emerged in clinical trials.
The drug giant is evaluating Danuglipron in a two-phase 1 dose optimization study. One of the patients in one of the studies suffered a potential drug-induced liver injury, the company said on Monday. This complication was resolved after the study drug was stopped.
Novo Nordisk and its GLP-1 agonists Wegovy and Eli Lilly, whose drug Zepbound activates GLP-1 and GIP receptors, currently dominates the obesity drug market. But both products are injections once a week. Pfizer is part of a growing group of competitors aiming to distinguish them from market leaders' districts by daily pill formulations.
Danuglipron was found inside Pfizer and is an oral small molecule designed to bind and activate GLP-1 receptors. The drug was initially targeted twice daily, while the interim results for 2023 showed statistically significant weight loss. But many study participants also stopped taking the drug, causing Pfizer to abandon plans to push the statement to a phase 3 test. Pfizer will shift its focus to developing the Danuglipron version of the day.
High levels of liver enzymes are potential signs of hepatotoxicity. Pfizer said that among more than 1,400 Danuglipron study participants, the total frequency of elevated liver enzymes was consistent with the approved GLP-1 drug. However, to be competitive in obesity, a drug needs to at least match the safety of currently available drugs, and any sign of liver damage is a red flag. At the end of last year, high levels of liver enzymes in stage 2 obesity led to the biology laboratory terminating the development of Azelaprag, a drug candidate for obesity, and tested in conjunction with Eli Lilly’s Zepbound. Pfizer said it decided to stop developing Danuglipron after reviewing all clinical data generated so far and the latest investment from regulators.
Liver enzymes have previously caught another Pfizer oral GLP-1 drug. Pharmaceutical giant stopped Lotiglipron's development in 2023 due to the elevated liver enzymes observed in the Phase 1 test. At that time, the company shifted its focus to Danuglipron. Pfizer said more detailed data on Danuglipron's clinical development plan will be presented at future scientific conferences or submitted for publication in peer-reviewed journals.
Pfizer still has other prospects for obesity. PF-07976016 is an oral drug designed to activate GIP receptors and is currently under phase 2 testing. Pfizer Pipeline lists another GLP-1 agonist, PF-0695-4522, an antibody that is being tested on Phase 1 for type 2 diabetes. But some analysts say Danuglipurun’s frustration could lead to Pfizer’s search for its next metabolic drug outside. William Blair analyst Andy Hsieh pointed out that Viking Therapeutics VK2735 is an agonist of GLP-1 and GIP receptors as a prospect.
The 3-stage test of the subcutaneous injection of VK2735 is beginning in the current quarter. Phase 2 testing of the oral version of Viking drug is underway and is expected in the third quarter of this year. Hsieh said in a study note that Viking drugs “can provide Pfizer with a rare opportunity to not only rebuild obesity, but also gain a lead in Novo Nordisk and Lilly Drugs.”
Leerink Partners Thomas Smith pointed to the VK2735 Phase 1B data provided during the Obesity Week Conference last November. Smith said in a note sent to investors that the weight loss and the low rate of gastrointestinal side effects compared to competitors and enhanced the drug’s best potential.
“In general, we believe that the discontinuation of Danuglipron further emphasizes the importance of efficacy and safety to obesity in competitive development settings and notes the striking clinical features of both to date [subcutaneous] and oral VK2735. ” he said.
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