Pfizer suffers another setback in the weight-loss drug race. Pfizer said that due to the high rate of adverse reactions caused by taking danuglipron twice a day, it has stopped research and development and will focus on experiments with danuglipron taken once a day in the future. Pfizer is facing obstacles as it seeks a piece of the weight-loss drug market.
On December 1, the American pharmaceutical giant Pfizer stated that due to the observed high frequency of adverse reactions, the twice-daily experimental weight loss drug danuglipron (a GLP-1 oral weight loss drug) will not enter Phase III studies.
Experimental results showed that up to 73% of patients experienced symptoms of nausea, up to 47% of patients experienced vomiting, and up to 25% of patients experienced diarrhea. Discontinuation rates were high across all doses, and looking at clinical trial statistics, a high discontinuation rate basically means that the drug has significant side effects that prevent the patient from continuing to take it.
It is understood that Lotiglipron and Novo Nordisk's blockbuster weight loss injections Ozempic and Wegovy belong to a class of drugs called glucagon-like peptide-1 (GLP-1) hormones. They mimic GLP-1, a hormone produced in the gut that signals the brain when a person is full. These drugs can also help people manage type 2 diabetes because they encourage the pancreas to release insulin, which lowers blood sugar levels.
Pfizer noted in the report that compared with the placebo group, patients in all Lotiglipron dose groups experienced an average weight loss of -8% to -13% at 32 weeks and -5% to -9.5% at 26 weeks.
In addition, Pfizer said that trials of once-daily danuglipron will continue in the hope that reducing the frequency of dosing will improve patient tolerance. Dr. Mikael Dolsten, Chief Scientific Officer and President of Pfizer Research and Development stated:
"We believe that reducing the dose of danuglipron to once-daily administration may play an important role in the treatment of obesity, and we will focus our efforts to collect data to understand its potential pharmacodynamic profile."
Analysts generally believe that the data of Pfizer's experimental weight loss drug danuglipron is the key to its entry into the weight loss drug market and competition with Novo Nordisk and Eli Lilly. Pfizer sees the "blue ocean" in the weight loss drug market and hopes to find another revenue growth point that can boost performance after the new crown drug.
Pfizer's abandonment of the research and development of its experimental weight-loss drug once again hit investors' confidence in its entry into the weight-loss drug market. After the news was announced, Pfizer's U.S. stock price fell by more than 5% before the market opened, and then the decline narrowed. So far this year, Pfizer's stock price has fallen by nearly 44%, approaching the low in March 2020.
Completely opposite to Pfizer's market trend, Eli Lilly's stock price has been rising this year, with two miracle drugs for "weight loss and Alzheimer's disease", with an increase of nearly 62% so far this year; the share price of Novo Nordisk, the leader in weight loss drugs, has increased by nearly 49% so far.
Pfizer's weight loss drug development suffers setbacks one after another
The more familiar peptide GLP-1 preparation in China is Novo Nordisk’s semaglutide, and the similar small molecule drug developed by Pfizer has a similar mechanism of action. Previously, Pfizer had deployed two small molecule oral GLP-1 agonist drugs, namely lotiglipron and danuglipron. Among them, lotiglipron needs to be taken once a day, and danuglipron needs to be taken twice a day.
Pfizer CEO Albert Bourla said the weight-loss drug could eventually bring the company $10 billion in annual revenue. The market is full of expectations for these two oral weight loss drugs, believing that oral administration may have more advantages than frequent injections.
But just in June this year, Pfizer announced that it would stop developing the weight-loss drug Lotiglipron due to elevated transaminases in patients taking the drug in mid-term clinical studies, a phenomenon that usually means damage to liver cells and liver function. But Pfizer said no patients experienced liver-related symptoms or side effects, and no patients developed liver failure or required treatment.
This allows Pfizer to develop danuglipron that can only be taken twice a day, but the market is generally not optimistic about this, because taking it twice a day is far less convenient than taking the drug once, and Pfizer's danuglipron needs to show a weight loss effect of "about 15%" to compete with Eli Lilly's orforglipron.
David Risinger, an analyst at Leerink Partners, an investment bank focused on health care, pointed out in an October report that in the Phase II trial, the proportion of patients who stopped taking Pfizer's twice-daily danuglipron may be higher than the proportion of patients who stopped taking Eli Lilly's orforglipron. This is partly because the total daily dose of danuglipron is much higher, which may lead to more adverse effects.
Risinger said Pfizer appears to believe that reducing the frequency of taking danuglipron to once a day can reduce gastrointestinal side effects. The bigger question for Pfizer now is whether once-daily danuglipron can proceed to Phase 3 trials in 2024, which is seen as a key step in obtaining approval from the U.S. Food and Drug Administration (FDA).
Pfizer is quite optimistic. During the company's third-quarter earnings conference call, Pfizer Chief Scientific Officer Mikael Dolsten said that the company is expected to conduct critical late-stage trials of a once-daily version of the drug next year.