On December 9th, Science and Technology Innovation Board Daily reported (Reporter Xu Hong) that "the market value of overseas leading companies has skyrocketed" and "A-share related sectors have been repeatedly hyped up". The explosive popularity of Smegglutide has brought a GLP-1 concept frenzy to the world.
Recently, Swiss pharmaceutical giant Roche's $3 billion investment once again ignited the GLP-1 weight loss concept.
However, driven by bullish sentiment, the benefits are often infinitely magnified, while the risks are often ignored. Focusing on differentiation, although Pfizer has proactively laid out small molecule GLP-1 oral weight loss drugs, it has repeatedly encountered setbacks in clinical trials, bringing more uncertainty to this research direction and also reminding everyone:
The gold rush GLP-1 seems to be becoming increasingly challenging.
GLP-1 Track AB: Some people are crazy, some people are rational
On December 4th local time, Roche Pharmaceuticals announced that it will spend over $3 billion to acquire Carmot Therapeutics, headquartered in Berkeley, California. According to public information, Carmot Therapeutics is committed to the research and development of metabolic disease therapies such as diabetes and weight loss, and holds several GLP-1 drugs under research, including two GLP-1R/GIPR dual target peptide agonists and one small molecule GLP-1 receptor agonist.
Coincidentally, in late November, Zhifei Biology, the domestic vaccine leader, also announced that it would purchase 100% of the equity of Chongqing Chen'an Biology in cash to cross the border from vaccines to metabolic diseases such as diabetes and obesity.
According to the merger announcement, Chenan Biotechnology currently has 6 candidate drugs that have entered the clinical stage, among which the recombinant Liraglutide injection and DeGu insulin injection have completed clinical phase III and are in the application for listing stage; Recombinant Smegglutide Injection is currently in Phase III clinical stage and its research and development progress is at the forefront in China.
The glucagon like peptide-1 (GLP-1) receptor agonist was originally just a new type of hypoglycemic drug, but it continued to gain popularity because it opened the door to the weight loss market.
"In the future, products with stronger consumer attributes are more likely to become heavyweight bombs, and weight loss indications belong to this category," someone once asserted. Moreover, GLP-1 drugs also have great potential for imagination in other major indications such as NASH (non-alcoholic fatty liver) and Alzheimer's disease.
Therefore, in addition to attracting more and more companies to accelerate their entry, the popularity of GLP-1 is even considered to disrupt multiple other industries such as traditional food and beverage. In October this year, after Novo Nordisk announced that Smeaglutide had made positive progress in delaying the progression of kidney disease in patients with diabetes, the stock prices of some overseas dialysis service providers also plunged.
Yan Feng (pseudonym) has been deeply involved in the field of metabolic diseases for many years and has rich experience in GLP-1 drug development. He is also very optimistic about the future prospects of GLP-1.
"GLP-1 can not only reduce blood sugar, but also reduce weight, and they come from different mechanisms of action. GLP-1 can also be seen as a kind of protective agent, which can protect many cells, including myocardial cells, nerve cells, etc. Therefore, in addition to the majority of diabetes patients, it is also expected to bring good news for heart failure and even AD patients." Yan Feng told the Science and Technology Innovation Board Daily.
However, while acknowledging the value of GLP-1 peptide drugs, Yan Feng also stated that "GLP-1 should not be deified.". "Not only GLP-1, but many other hypoglycemic drugs can also bring multiple clinical benefits, such as metformin having cardiovascular protective effects in addition to lowering blood sugar, and SGLT-2 inhibitors significantly reducing kidney risk," he said.
It is reported that Yan Feng's company has comprehensively laid out the GLP-1 pipeline, and is promoting both diabetes and obesity indications. In his opinion, although the weight loss track market has a large space, we also need to be alert to the existence of foam, "because many people who are not obese are also using Smeaglutide to lose weight," he said.
Oral peptides, the ultimate hope for overtaking on curves?
With the rapid expansion of players, the competition on the GLP-1 track is constantly intensifying. According to incomplete statistics, there are currently 333 GLP-1RA projects worldwide, and there are also 112 new GLP-1 drugs entering the clinical stage in China. From the number of project applications, clinical applications have been in an explosive period in the past three years. This means that the development of GLP-1 drugs urgently needs further differentiation.
Multi target and oral administration are recognized as the two main directions for the development of GLP-1 drugs. Gu Lin (pseudonym) is one of the earliest investors in China to focus on weight loss and GLP-1 peptide drugs. He explained to a reporter from the Science and Technology Innovation Board Daily that developing multi target GLP-1 drugs is to pursue better therapeutic effects, while oral drugs have better compliance and are also more in line with the trend of consumer medicine.
It is reported that currently, both marketed and clinically active GLP-1 drugs are mostly composed of macromolecular proteins, with subcutaneous injection being the main method of administration, resulting in poor patient compliance.
Perhaps it is also because Pfizer has seen the potential of "oral" drugs to overtake in the curve, so Pfizer is fully betting on this research and development direction, and several core products in the pipeline are oral small molecule GLP-1 agonists.
However, this road is not easy to follow. On December 1st, Pfizer announced to the public that due to the high frequency of observed adverse reactions, the experimental weight loss drug danuglipron, which is taken twice a day, will not enter the Phase III study. This is already the second small molecule GLP-1 oral medication under Pfizer in the past six months to break through. In June of this year, Pfizer also abandoned the development of another small molecule GLP-1 drug, Lotiglopron, due to safety reasons.
In this regard, Gu Lin also pointed out to a reporter from the Science and Technology Innovation Board Daily that the difficulty in developing small molecule GLP-1 oral formulations is the significant side effects. "And not only Pfizer, but other similar products being promoted in clinical practice may also have similar problems," he told reporters.
However, the development of GLP-1 oral drugs is classified by component type, in addition to small molecules, there are also oral peptides. In Gu Lin's view, the latter may have a higher chance of success in weight loss indications.
"Among them, oral small molecule therapy is Pfizer's chosen direction, while Novo Nordisk focuses on oral peptides. Regardless of which direction, it is actually difficult to obtain weight loss indications. However, relatively speaking, I would be more optimistic about the latter." Gu Lin said that from the FDA's approval of the first oral peptide drug on the market in 2019- Rybelsus oral smeglutide, to the approval of oral octreotide in 2020, peptide drugs have entered the era of oral administration.
"However, as of now, the oral peptide GLP-1 has not been approved as an indication for weight loss. Oral peptide drugs mainly have low bioavailability, but as long as this problem can be solved, they can be used for weight loss." Gu Lin said that there are currently a number of domestic enterprises targeting this direction, hoping to achieve oral administration of biological preparations, including peptides, through better oral delivery technology, including Denglong Biotechnology and Shenzhen Aoli Pharmaceutical.
On the GLP-1 weight loss track, it can be seen that Chinese biotech companies have begun to emerge. After cutting off two GLP-1 drugs in succession, AstraZeneca and Chengyi Biotech reached an exclusive partnership of over $2 billion in November this year for the oral small molecule GLP-1 drug ECC5004.
In the future, the Science and Technology Innovation Board Daily will continue to pay attention to whether China's R&D forces can continue to exert their efforts and achieve overtaking on curves on this 100 billion dollar track.