Tirzepatide enters another 10 billion market

January 2, 2025  Source: drugdu 154

"/Recently, Eli Lilly announced that the FDA has approved Zepbound (tirzepatide) for the new indication of treating moderate to severe obstructive sleep apnea (OSA) in obese people. While using Zepbound, you should reduce your calorie diet and increase physical exercise.

The approval of the OSA indication has given Eli Lilly another heavyweight bargaining chip in its competition with its strongest rival Novo Nordisk.

Obstructive sleep apnea (OSA) is a respiratory disease in which apnea and/or hypopnea occur repeatedly during sleep. During sleep, the throat and tongue muscles relax, leading to airway obstruction, and air circulation is blocked, causing apnea or weakening of breathing. OSA is common in obese and middle-aged and elderly people, and can cause complications such as coronary atherosclerotic heart disease, heart failure, arrhythmia, and diabetes. Clinical manifestations include snoring, loud snoring, feeling suffocated or waking up at night, and severe cases of cognitive decline and abnormal behavior.

According to Frost & Sullivan data, according to the 2012 American Academy of Sleep Medicine judgment criteria, from 2020 to 2025, the number of people aged 30-69 years old worldwide is expected to increase from 1.07 billion to about 1.16 billion. China has the highest prevalence of OSA, and it is expected that the number of people with OSA in China will reach 210 million by 2025.

According to relevant estimates, the global OSA drug market size will reach US$9.2 billion (approximately RMB 67 billion) in 2021, and the compound growth rate is expected to reach 4% from 2022 to 2028. However, in the past 40 years, there has been little significant progress in the treatment of this disease, and it still mainly relies on non-drug intervention treatment. For example, many patients need to use positive airway pressure devices (PAP) to maintain ventilation during sleep, but this treatment effect is very limited, and many patients find it difficult to adapt to the discomfort caused by wearing. Telpotide is the first drug approved by the FDA for direct treatment of OSA, breaking the long-term dilemma of no clear indication for the disease, marking a new era for OSA treatment.

As the world's first GLP-1/GIP dual receptor agonist to be launched, telpotide has been approved for hypoglycemic and weight loss indications. According to global sales data, in the first three quarters of this year, the weight loss version of telpotide (Zepound) had revenue of US$3.018 billion, and the hypoglycemic version (Mounjaro) had revenue of US$8.01 billion. The two together contributed US$11.028 billion in revenue, accounting for about 34% of Eli Lilly's total revenue in the first three quarters.

So far, the treatment field of telpotide has expanded to endocrine and metabolic diseases, respiratory diseases, etc. In addition to hypoglycemic, weight loss and the "freshly baked" OSA indication, telpotide's next gold mine has chosen the fortress that has not yet been conquered in the cardiovascular field: heart failure. In November this year, Eli Lilly submitted an application for the marketing of tirpotide to global regulators for the treatment of patients with heart failure with preserved ejection fraction (HFpEF) and obesity.

This application for marketing is based on the positive results of the SUMMIT (Tirpotide in HFpEF and Obese Patients) Phase III clinical study. The results showed that compared with placebo, tirpotide reduced the risk of heart failure events by 38% and reduced the risk of hospitalization due to heart failure by 56%. In addition, the KCCQ-CSS (used to assess symptoms and physical function limitations associated with heart failure) questionnaire score of tirpotide improved by nearly 25 points, while the improvement in the placebo group was only 15 points. Currently, patients with heart failure with preserved ejection fraction (HFpEF) face severe symptom burden and functional impairment, and obesity is one of the main factors driving the progression of HFpEF. Although existing heart failure drugs have a certain effect on HFpEF patients, the overall efficacy is limited, and there are few treatment strategies for obesity. Tirpotide has great potential to fill this gap.

In addition, the indications of tirpotide under development include plaque psoriasis (PSO), non-alcoholic steatohepatitis (NASH), chronic kidney disease (CKD) and morbidity and mortality in obese patients (MMO), etc., and more than 140 clinical studies have been conducted.

As the user population continues to expand, the huge defects of GLP-1 weight loss drugs are gradually exposed. Data show that nearly 40% of the weight lost by semaglutide subjects is muscle, and muscle loss increases the risk of cardiovascular disease and osteoporosis. Tirpotide is also difficult to avoid this problem, so it is urgent to develop a better "fat loss and muscle gain" combination therapy. Based on this, Eli Lilly has bet on the biotech startup BioAge early. Its preferred candidate drug is a small molecule, oral Apelin receptor agonist-Azelaprag, which has previously conducted a phase 2 clinical trial of combined treatment of obesity with Eli Lilly's tirpotide.

However, there are unexpected events. Only three months after the IPO, on December 6 this year, BioAge announced that the company had decided to stop the STRIDES Phase 2 study of Azelaprag as a monotherapy and in combination with telpotide. The reason is that 11 of the 204 subjects recruited in the STRIDES Phase 2 study had elevated transaminases. They appeared in the Azelaprag treatment group and the Azelaprag + telpotide combination therapy group. However, in the control group using only telpotide, there was no elevated transaminases. This also means that there are serious problems with the safety of Azelaprag, and it also announces that Eli Lilly's "fat loss and muscle gain" has fallen.

Fortunately, in addition to Azelaprag from BioAge Labs, Eli Lilly is currently planning or cooperating with molecules in the direction of "fat loss and muscle gain". There are also Bimagrumab from Versanis, which was acquired for US$1.925 billion last year, and LAE102 from Laika Pharmaceuticals, which has just started clinical cooperation. These two drugs have one thing in common: they both act on the ActRII target. ActRII not only exists in muscle cells, but also plays an important role in fat cells. Signals sent through the ActRII receptor can lead to fat accumulation and muscle atrophy, so blocking this signaling pathway can both reduce fat accumulation and promote muscle growth. Therefore, when Eli Lilly focuses on product lines that can complement tirpotide, ActRII antibodies that can increase muscle and reduce fat are undoubtedly its key considerations.

Bimagrumab is an ActRIIA/B dual-target antibody. In October this year, Eli Lilly officially launched a Phase II clinical trial of Bimagrumab combined with tirpotide for muscle gain and fat loss. Unlike Bimagrumab, which targets both ActRIIA and ActRIIB, LAE102 is a single-target antibody that only inhibits ActRIIA. In terms of fat loss and muscle gain, whether targeting ActRIIA or ActRIIB alone is a better solution than inhibiting both ActRIIA and ActRIIB at the same time is not yet determined. Eli Lilly chose to make two preparations and bet on single/double-target antibodies of ActRII at the same time, showing its confidence in winning the track and its determination to ensure that everything is foolproof.

According to relevant forecasts, the sales of tirpotide are expected to surpass semaglutide in 2029, reaching a forecast sales of US$27 billion. In order to achieve this feat, Eli Lilly has made steady progress, not only "making great efforts" in weight loss indications to lay out the next generation of "fat loss and muscle gain" tirpotide combination therapy in advance, and continue to strengthen its moat in this advantageous field, but also a number of long-awaited cross-therapeutic indications are about to usher in an intensive harvest period.

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