Danuglipron: Is Pfizer’s oral weight loss pill a contender in the obesity market?

As the obesity drug market continues to soar, numerous biotech companies are attempting to create weight loss drugs that are either administered orally or that are more effective than Wegovy and Zepbound, to compete with leaders of the field Novo Nordisk and Eli Lilly. Now, Pfizer, another giant of the biopharma industry, believes it has selected a worthy glucagon-like peptide 1 (GLP-1) candidate, called danuglipron. 

Danuglipron is an oral, once-daily weight loss pill, as Pfizer looks to ride the next wave in the obesity market, which is calling out for effective oral products to become available in order to make it more convenient for the people taking them. But with so many companies having the same idea, the competition is heating up to the extent that it is driving prices for Wegovy down, and it is a race to see who will be the quickest at gaining approval for their drugs. 

Oral weight loss pills: The next wave in the obesity market  

As touched upon, oral weight loss pills are the next big thing in the obesity market, as they could help to increase the market size even further due to their convenience compared to injections – which is how current obesity drugs like Wegovy are currently administered. 

“The choice between a daily tablet or weekly injection for obesity has the potential to offer patients and healthcare providers the opportunity to choose which suits individual treatment preferences,” said Martin Holst Lange, Novo’s executive vice president of development, in a company press release.

Despite being injectable, the demand for Wegovy has still been extremely high. Novo recently said that it has been increasing its supply of Wegovy, with at least 25,000 people now starting to take the medicine each week in the U.S., up from 5,000 in December. If people were offered an oral alternative that was just as effective, it is fair to assume that the demand could be even higher. 

Another advantage of oral options is that they are easier to manufacture than injections – which come in the form of single-use pens – meaning that oral obesity drugs could potentially help alleviate the supply shortages that have plagued Novo’s and Lilly’s injectable counterparts. Pills are also generally cheaper than injections, though it is unclear if that will be the case with obesity pills. 

Pfizer finds a formulation of danuglipron with a “favorable profile”

On Thursday, July 11, Pfizer announced that it had selected its preferred once-daily modified-release formulation for danuglipron and said that it would advance the development of this candidate. This comes after the clinical evaluation of several modified-release once-daily formulations of danuglipron resulted in “encouraging pharmacokinetic data” for several candidates, with one showing the most favorable profile. 

Mikael Dolsten, chief scientific officer & president, Pfizer Research and Development, said in the press release that danuglipron has demonstrated good efficacy in a twice-daily formulation and that a once-daily formulation “has the potential to have a competitive profile in the oral GLP-1 space.” Essentially, this could help Pfizer in the race against rivals such as AstraZeneca, Eli Lilly,  Structure Therapeutics, and Viking Therapeutics.

The ongoing pharmacokinetic study being conducted by Pfizer is evaluating the pharmacokinetics and safety of immediate- and modified-release formulations of oral danuglipron in healthy adults 18 years or older. To date, study results have demonstrated a pharmacokinetic profile supportive of once-daily dosing, with a safety profile consistent with previous danuglipron studies, including no elevated liver enzymes in patients. 

Pfizer, back from the brink after axing twice-daily danuglipron 

Although this now seems like good news for Pfizer, for a while, it looked like the company had tried and failed to make its mark in the obesity area.

In fact, this once-daily version of danuglipron came about after Pfizer had to drop twice-daily danuglipron back in December 2023 after high discontinuation rates – greater than 50% – were seen across all doses compared to approximately 40% with placebo. This was potentially due to adverse events caused by the drug, as 73% of participants experienced nausea, 47% reported vomiting, and 25% suffered diarrhea. 

Furthermore, before that, Pfizer also had to discontinue the development of its other oral once-daily GLP-1 candidate lotiglipron, after clinical trials showed elevated transaminases, a type of enzyme that can be an indicator of liver dysfunction.

But Pfizer, persistent in its mission to develop an obesity candidate, kept rolling its pharmacokinetic study of the once-daily version of danuglipron even after axing the twice-daily version of the molecule, and it seems it finally has its lead GLP-1 candidate to take to the market. 

What is next for danuglipron?

Although Pfizer has finally settled on a promising version of danuglipron, it still has a long way to go as it needs to conduct large-scale clinical trials to produce the necessary data to show it’s safe, effective, and tolerable before submitting any sort of request to the U.S. Food and Drug Administration (FDA). The company said it plans to conduct dose optimization studies in the second half of 2024 evaluating multiple doses of the preferred modified release formulation to inform the registration enabling studies.

The good news is that the move to advance with a once-daily version of danuglipron appeared to sit well with investors, as Pfizer stock rose more than 3% in morning trading on the day of the announcement. With two other oral weight loss candidates in its pipeline with undisclosed mechanisms of action, obesity is an area that Pfizer desperately wants to break into, which is no surprise considering how lucrative the obesity market currently is. 

But this also means there is a lot of competition; ultimately, it is a race to see who can develop the best obesity pill and squeeze into the market alongside Novo and Lilly. Analysts project that the global market for obesity drugs will be $120 billion by 2031, and most of the market will be relatively split between Novo and Lilly, both of whom are already dominating when it comes to obesity drugs. Meanwhile, the overall market for GLP-1s is seen as even larger, at some $170 billion. It is forecast that over 25% of obese Americans and 15% of overweight Americans will receive treatment in 10 years, and the vast majority will receive branded GLP-1 therapies.

Speaking at an investor event last month, the chief executive officer (CEO) of Pfizer said that danuglipron was two years behind Eli Lilly’s oral candidate and two years ahead of AstraZeneca’s program. Although it is unlikely it will be approved before Lilly’s or Novo’s candidates, if Pfizer manages to avoid any additional hurdles along the way, danuglipron might just be a plausible contender in the race against other companies looking to achieve the same oral obesity drug milestones. 

Tough competition: The biggest players in the oral obesity drug race

In terms of danuglipron’s main competitors, let us take a closer look at some of the biggest players operating in the area of oral weight loss pills.

Novo Nordisk

As you might expect, Novo is competing against itself in this area and is developing an oral version of Wegovy. Its product Rybelsus is already on the market – in fact, it is the only oral GLP-1 drug currently available to buy – but it is only indicated for adults with type 2 diabetes. 

However, last year, Novo reported that data from a phase 3a trial showed that a high-dose oral version of semaglutide – the active ingredient in Wegovy, Ozempic and Rybelsus – performed comparably to the injected version. In the study, patients who received a 50mg daily dose of the drug lost an average of 15.1% of their weight over 68 weeks, compared with a 2.4% average weight loss for those on placebo. Novo is now waiting to seek U.S. and European regulatory approval on this. 

Additionally, Novo is developing another oral weight loss pill called amycretin – a GLP-1 and amylin receptor agonist – that recently outperformed Wegovy in a phase 1 trial. Early results from this trial showed that patients on amycretin lost around 13.1% of their weight after 12 weeks compared to just 1.1% of patients taking placebo, surpassing the 6% weight loss seen in those who took Wegovy over a similar time frame. According to Novo, a mid-stage trial for amycretin will begin in the second half of this year, with results expected in early 2026. 

Eli Lilly 

Just as with Novo, it will come as no surprise that Lilly is also developing an oral weight loss candidate to bring to the market. Called orforglipron, the company’s pill is a GLP-1 receptor agonist. It achieved positive results in a phase 2 trial, in which overweight or obese adults who took 45mg of orforglipron once a day lost up to 14.7% of their body weight after 36 weeks, compared to 2.3% for people in the placebo group. These results are similar to the weight reduction caused by Novo’s pill, but they were achieved over a shorter trial period, meaning that orforglipron could potentially achieve an even greater level of weight loss over a longer trial period – something that will be tested during phase 3 studies. Lilly announced in April that it had already begun phase 3 trials for the drug in India. 

Roche

Earlier this month, promising early-stage trial data from Roche’s oral obesity drug made Novo’s and Lilly’s shares slide. Roche picked up the once-daily GLP-1 candidate, called CT-996, from its acquisition of Carmot Therapeutics. A phase 1 trial showed that participants with obesity – but not type 2 diabetes – lost 7.3% of their body weight after four weeks of treatment. There are some gaps in the data provided by Roche, such as weight at baseline, which make cross-trial comparisons difficult, but the available evidence suggests CT-996 could be competitive against Novo’s and Lilly’s candidates. The next part of the phase 1 trial, which Roche plans to start in the fourth quarter, will enroll two sequential cohorts of 30 participants with obesity and type 2 diabetes. 

Viking Therapeutics

Biotech company Viking Therapeutics also recently announced positive topline results from a phase 1 study of its oral obesity candidate VK2735, which targets both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), another insulin-stimulating hormone. During the trial, seven people taking the high dose of 40mg experienced an average weight loss of 5% from the mean baseline weight of 90 kilograms. Adjusted against the weight loss reported among the placebo group, the average reduction was 3.3%. Viking now plans to begin a phase 2 trial later this year.

AstraZeneca

AstraZeneca re-entered the obesity drug race last November when it paid Eccogene $185 million to license an oral GLP-1 drug called ECC5004, just months after the British-Swiss multinational had discontinued its own oral GLP-1 candidate. As of yet, there is not much data for ECC5004, but AstraZeneca said that preliminary results from a phase 1 trial have shown a “differentiating clinical profile” for ECC5004, with “good tolerability and encouraging glucose and body weight reduction across the dose levels tested compared to placebo.”

With many of heavyweights of the biopharma industry competing against one another, the oral obesity market is likely to be an extremely lucrative one. But how many of them will manage to break into it? Only time will tell.