Recently, the Q3 financial reports of MNCs have been released one after another, and some are happy and some are sad. When a number of MNCs began to lower their full-year EPS, Amgen's Q3 financial report earnings gave a high score answer sheet. Among them, Amgen's total revenue in the third quarter increased by 23%, and its GAAP net earnings per share (EPS) increased by 62% year-on-year, from US$3.22 to US$5.22.

What is more imaginative is that with the data catalysis of the new macromolecular weight loss drug AMG133, this macromolecular antibody that goes against the grain and antagonizes GIPR may become Amgen's next gold mine.

According to Amgen's Q3 2024 financial report, the most significant year-on-year growth is LUMAKRAS (AMG510) - a targeted drug for KRASG12C mutation-positive lung cancer.

The sales ceiling of this gene mutation in European and American countries will be much higher than that in Asian countries. This is mainly due to the racial differences in this gene mutation. According to the article "Distribution of KRASG12C Somatic Mutations across Race, Sex, and Cancer Type" published in the New England Journal, among NSCLC patients, the proportion of KRASG12C mutations in white and black patients is significantly higher than that in Asian patients. The proportion of white patients reached 13%, the proportion of black patients also exceeded 10%, and the proportion of this gene mutation in Asian patients was only 3.6%.

In 2021, the drug was approved in the United States and Europe, and at the beginning of the following year, the drug was launched in Japan; but the drug's revenue was also relatively bumpy. In Q3 2022, its revenue reached US$75 million, but in Q3 2023 it was only US$52 million. In Q3 this year, the drug returned to the high-speed growth track with revenue of US$98 million. This is mainly due to the opening of markets outside the United States. In Q3 2023, revenue from countries and regions outside the United States was only $4 million, while this year's Q3 has reached $45 million, a tenfold increase year-on-year.

In addition to the lung cancer targeted drug LUMAKRAS, the tumor drug BLINCYTO also contributed a relatively steep growth curve - from $220 million in the same period last year to $327 million this year, a year-on-year increase of 49%.

BLINCYTO is Blinatumomab, a CD19/CD3 bispecific antibody, which is a very hot TCE bispecific antibody type in the research and development community. It uses CD3 targets to link T cells and CD19 to link target cells, allowing T cells to specifically kill target cells.

The hot topic of recent discussion is that TCE bispecific antibodies may reduce the cost of CAR-T therapy in the field of autoimmunity, and will also have a good effect in dealing with solid cold tumors such as SCLC. But the starting point of TCE bispecific antibody research and development is hematological tumors. Blinatumomab can be said to be a pioneer of TCE bispecific antibodies in the field of hematological tumors. It was approved by the FDA in 2014 and by the EU the following year. At present, its sales in one quarter have reached 327 million US dollars, which is a great achievement in commercialization.

In addition, the initial sales of tarlatamab, the first TCE bispecific antibody for solid tumors, is also worth paying attention to. The drug was approved in May this year, and the third quarter was the first full sales season: the first full sales quarter reached 36 million US dollars. There is still no sign of slowing down.

Finally, its old anti-tumor drug Vectibix (panitumumab) also contributed 12% growth. The drug antagonizes EGFR targets and is mainly used for the treatment of colorectal cancer. The revenue in Q3 this year also reached 327 million US dollars.

Revenue climbing in areas other than tumors

In areas other than tumors, its main products Repatha and EVENITY contributed the main growth.

Repatha is Elocumab, which targets PCSK9 and is a representative macromolecular drug in the field of lowering blood lipids. It mainly inhibits the binding of PCSK9 to LDLR (low-density lipoprotein receptor), resulting in an increase in the number of LDLR that can clear low-density lipoprotein in the blood, thereby reducing LDL-C levels. It has been nearly ten years since the drug was approved for marketing. In 2015, the drug was approved by EMA and FDA for marketing in the EU and the United States, and was approved for marketing in my country in 2018.

The drug also faces many competitors, among which the macromolecular drug with the same mechanism is Alirocumab, which was jointly developed by Regeneron and Sanofi and was also approved for marketing in 2015. In addition, one of the main directions of RNAi therapy is the field of lowering blood lipids, which can be seen from the sales of Inksilan: its sales in 2022 are US$112 million, and in 2023 it will soar by 217% to US$355 million. In addition, there are many similar RNAi pipelines.

Under such market competition, it is not easy for eloumab to maintain such growth.

EVENITY is romosozumab-aqqg. The main indication of this monoclonal antibody is osteoporosis. It was approved by the FDA in 2019 and is the world's first monoclonal antibody targeting sclerostin. Sclerostin, also known as sclerostin or osteosclerostin, inhibits bone formation by binding to low-density lipoprotein receptor-related protein 5/6 (LRP5/6) to inhibit the Wnt/β-catenin signaling pathway. Therefore, overexpression of this protein may lead to the possibility of osteoporosis. Evenity promotes bone formation by inhibiting this protein. In addition, it also inhibits bone resorption to treat osteoporosis.

Since its approval, the sales of the drug have also shown a climbing trend. In 2022, the sales reached US$787 million, a year-on-year increase of 48%; and the full-year sales in 2023 reached US$1.16 billion, a year-on-year increase of 47%. The revenue in Q3 this year increased by 30%. After several years of rapid growth, there is a certain slowdown trend. We can wait for further verification in the annual report.

The drug TEZSPIRE in the field of inflammation achieved revenue of US$269 million in the third quarter, a year-on-year increase of 67%. The drug is the first TSLP monoclonal antibody for the treatment of asthma and was approved for marketing by the FDA in 2021. In the future, the indications of the drug will not be limited to asthma. In August this year, it was recognized as a breakthrough therapy by the FDA for the treatment of COPD, and the Phase III clinical trial is also being launched in an orderly manner. In addition, the drug will also expand its indication space in inflammations such as allergic rhinitis and sinusitis with nasal polyps. It should be said that the sales ceiling of the drug is far from being reached.

In addition, Amgen's highest-selling single product this quarter is Prolia, with revenue reaching US$1.045 billion. The drug is Desmodium, which was approved by the FDA in 2010. It can be regarded as a representative drug for the treatment of osteoporosis before EVENITY. After nearly 15 years of sales, the drug is currently facing many biosimilar challenges, but it can still achieve a 6% revenue growth, with sales exceeding $1 billion in a single quarter.

In addition to the revenue growth of commercialized products, the recent clinical data catalysis is also worth paying attention to, which may become Amgen's next gold mine.

The focus is naturally on the readout of the year-end data of AMG133. As a dual-target drug for GLP-1/GIPR, this drug is different from other related drugs, and it can even be said to be uncharacteristic. Other drugs are in the form of small and medium-molecule peptides, some of which are similar to Eli Lilly's Ogliron in the form of small molecule drugs, while Amgen's AMG133 is in the form of antibodies. This kind of drug formation can be speculated to be for Amgen's ultimate goal: antagonizing the GIPR target.

As we all know, many current drugs are in the form of tirpotide, which are made into dual-target agonists, that is, they have an agonist effect on GIPR. The reason why Amgen chose to antagonize the GIPR comes from the basic research they did. According to the mechanism described in the paper "Chronic glucose-dependent insulinotropic polypeptide receptor (GIPR) agonism desensitizes adipocyte GIPR activity mimicking functional GIP antagonism" published by Amgen scientists, long-term GIPR stimulation can lead to GIPR desensitization and no longer respond to subsequent GIP stimulation, thus ultimately playing an antagonistic role. In addition, the possible endocytosis effect will also lead to its actual antagonistic effect.

This is the underlying logic of Amgen's development of AMG133. And from its Phase I clinical data, the data is indeed amazing: patients treated with a dose of 420 mg of AMG 133 had an average weight reduction of 14.5% compared with baseline at about 12 weeks, which is slightly better than the weight loss effect of Noxinord's compound preparation Cagrisema. Of course, the current clinical sample size is not large, only 6 people.

Because of this, the percentage of weight loss that can be achieved in the 24-26 week data of the Phase II clinical trial is even more exciting.

At 8:30 a.m. Central Time on November 3, Viking announced the latest Phase I clinical data of the oral version of its core weight loss pipeline VK2735 at the American Obesity Association Annual Meeting - patients taking a 100 mg dose of VK2735 lost an average of 8.2% weight after 28 days (4 weeks). This weight loss effect is 6.8 percentage points higher than the placebo group, and it breaks through the ceiling of the previously released oral version of the 40mg upper dose. In terms of safety and tolerability, at the highest dose, no patient discontinued treatment, confirming its good safety.

At present, VK2735 can be said to be the best in class among GLP-1/GIPR peptides of the same class, and it is also the only pipeline of dual-target drugs of the same class that has developed oral therapy. At present, Viking's stock price has also ushered in a surge of more than 13 percentage points.

Every move in weight loss clinical data affects everyone's expectations of the company. Amgen's AMG133 may be the next launcher to drive Amgen's rocket into takeoff.

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