Who is the king of domestic innovative drug rolls?
R & D pipelines are piled up in the field of anti-tumor, especially the major indications for lung cancer, the same pharmaceutical company layout single drug + a variety of combination therapies, there is a Situation of Zhou Botong-style left and right hand mutual knowledge.
According to the statistics of the Drug Review Center of the State Food and Drug Administration, the targets of the top 10 registered trials in 2020 are PD-1, CYP51A1, VEGFR, PD-L1, DNA, microtubules, EGFR, HER2, PARP, GLP-1R, of which the number of trials registered in the first three targets exceeds 60. In addition to GLP-1R, which is associated with diabetes treatment, the other 9 targets focus on the field of tumor therapy.
Homogeneous competition leads to the waste of clinical resources, less than half of the subject recruitment within 1 year after the clinical trial is approved, and even 20% of the clinical trial approval documents have not been able to start recruitment after the expiration of the 3-year validity period.
Innovative drugs are in the cooling-off period, and they need to start with the end and design pipelines according to the market-oriented orientation.
In addition to the track of the group chase, there is a vast world, and the moon is rare. In the differentiated areas with low competitive intensity, there is also a large market, and it is easier to run out of explosive drugs.
Due to the eating habits of Chinese people with three highs and one low (high fat, high protein, high calories and low fiber), there is a huge unmet clinical demand in the field of digestion. According to Frost & Sullivan, the expected market size of domestic gastrointestinal drugs in 2023 is 158 billion yuan.
Many people have experienced reflux and heartburn symptoms caused by excessive gastric acid secretion after meals, and the domestic acid-suppressing drug market space is vast, currently dominated by proton pump inhibitors (PPIs), and the PPI market size in 2019 reached more than 30 billion yuan.
The first domestic new generation of acid suppressant drugs has been listed, And Luoxin Pharmaceutical's 1-class new drug teigora tablets have the advantage of comprehensively replacing existing PPI drugs, and are expected to become 5 billion explosive drugs.
01
Two magical curves
Due to lifestyle changes, milk tea, coffee, fat fairy water (cola), cream, desserts, barbecue are popular, and the prevalence of gastroesophageal reflux disease (GERD) has shown an upward trend in recent years.
Regurgitation of gastric and duodenal contents causes esophageal mucosal damage, and endoscopic erosion and ulceration of the esophagus may be seen.
Repeated heartburn, reflux, mildly affect sleep, diet, and others lead to complications such as esophageal stenosis, ulceration, bleeding, and Barrett's esophagus, which is a precancerous lesion.
The prevalence of heartburn symptoms at least once a week in mainland China is 1.9% to 7.0%, the prevalence of GERD is 4.1%-7.3%, and the population of 57 million to 103 million people is deeply troubled.
Acid-suppressing drugs have always had a blockbuster physique.
Traditional PPI drugs have many shortcomings, short half-life, insufficient acid suppression, limited medication time, slow onset of action, obvious side effects, but sales have created a magical curve.
In 2019, among the drugs used by domestic public medical institutions for the treatment of peptic ulcers, PPI drugs dominated the top ten in terms of sales, with annual sales of more than 1 billion yuan.
Epprazole belongs to the irreversible proton pump inhibitor (PPI), which is the first major product of Livzon Group, creating a miracle of volume. Eparazole sodium for injection was approved for listing in January 2018 and was included in the national medical insurance through negotiations in 2019, and the sales growth rate in the past three years has reached three digits.
In 2021, the sales revenue of the eparazole series (oral enteric-coated tablets + injection) will be about 3 billion yuan. In the first quarter of this year, it is expected that the sales volume of eprazole injections will increase by more than 50% year-on-year, and the sales of tablets will increase by more than 30% year-on-year.
Takeda Pharmaceutical's Vonorason is a new generation of acid-suppressing drugs P-CAB, with global revenues of $668 million and $794 million in 2019 and 2020, respectively, in continuous volume.
02
The strongest acid-suppressing drug
P-CAB is a new type of potassium ion competitive acid blocker that can reversibly block the proton pump that secretes gastric acid, and is expected to replace the PPI market share and become a mainstream acid-suppressing drug.
Compared to PPI, P-CAB has comprehensive clinical advantages:
Active drug, no need for acid activation after eating, the effect of the drug is not affected by meals.
Long half-life, long inhibition of gastric acid secretion (19 hours), only need to take the drug once a day.
Rapid acid suppression, onset of action within 0.5 hours after taking the drug, blood concentration within 1 hour can reach the peak.
The first dose is fully effective, without the need to take the drug for several days to accumulate and add up to achieve the best results.
Throughout the day and night, it can solve the phenomenon of nocturnal acid breakthrough and maintain stable symptom control.
Good compliance, no need to make enteric-coated preparations, will not cause difficulty swallowing.
There are 4 P-CAB drugs approved for marketing worldwide, and only 2 in China. In April this year, Luoxin Pharmaceutical's 1 new drug Tigora raw tablets was approved for listing, becoming the first domestic P-CAB drug for the treatment of reflux esophagitis. Compared with competitor Takeda Pharmaceuticals Vonorasine, Tegora has a faster onset of action, does not cause elevated liver enzymes, and has a smaller risk of drug interaction (DDI).
Tigolas has a remarkable effect, with a mucosal healing rate of 97.5% in moderate to severe RE (reflux esophagitis) at 4 weeks.
The competitive landscape is loose. Vonorason's patent in China will expire in 2026, and generic drugs will not be able to impact new drugs in the short term. Yangzijiang Pharmaceutical introduced the interests of non-Surazin (P-CAB) in China at a cost of up to 2.2 billion yuan, and launched phase I clinical trials in July last year, which is still far from listing. Ko Norazan, developed by Kofiping Pharmaceuticals, was accepted on September 30 last year and is expected to be approved next year.
Tigorassen is expanding two indications with a larger patient base.
The prevalence of duodenal ulcer (DU) is about 7.5%, the number of domestic patients is 105 million, and the clinical manifestations are persistent pain in the epigastric region, severe patients sleep and daily life, accompanied by perforation and complications of gastrointestinal bleeding.
Helicobacter pylori is a world-class carcinogen. Epidemiological studies have shown that more than half of the world's population is infected with Helicobacter pylori, and at least 700 million people on the continent are infected with Helicobacter pylori. Meta-analyses have shown that the incidence of gastric cancer in infected patients with Helicobacter pylori eradication is lower than that of infected people who have not received eradication therapy, and the risk of gastric cancer development can be reduced by half. The market for the eradication of Helicobacter pylori infection in combination with appropriate antimicrobial therapy is promising.
The two indications for tegora tablets duodenal ulcer and Helicobacter pylori infection are currently in the clinical phase III trial and are expected to be approved for marketing around 2024.
Rosin Pharmaceuticals will also develop teigoras injection dosage forms for application scenarios including but not limited to major gastrointestinal surgeries and patients with severe ICU disease. Tigorasim injection is not yet available worldwide.
In the sales scale of digestive system and metabolic drugs in public hospitals, drugs for the treatment of gastric acid-related diseases are second only to diabetes drugs and are the second largest drug market.
According to the analysis of Zheshang Securities, P-CAB gradually replaces PPI in the domestic peptic ulcer and gastroesophageal reflux disease potential drug space is large, and it is expected to be about 100 billion to 150 billion yuan.
Covering the three major indications in the field of digestion, the peak sales of Tigoras are expected to reach the level of 5 billion yuan in 3 to 5 years.
03
Breakout under double squeeze
Faced with the double squeeze of Biotech and collective procurement, the performance of established pharmaceutical companies generally fluctuates, but the advantages are strong survival resilience and accurate business vision.
CSPC Pharmaceutical Group has been in a slump for 2 years, and finally climbed out of the quagmire, balanced the development of innovative drugs, and expanded the circle of capabilities to mRNA vaccines. Huadong Pharmaceutical gradually eliminated the negative impact of acarbose and pantoprazole collection, Bailing capsule medical insurance negotiations, starting from Q4 last year, deducting non-net profit to maintain positive growth, multi-line layout of medical beauty, synthetic biology, CDMO, innovative drugs. Kelun Pharmaceutical basic digestion of the impact of collection, the first quarter of this year's net profit of 291 million yuan, an increase of 66.09% year-on-year, the long-term drag oil bottle Chuanning Biology finally perked up, to achieve a net profit of 101 million yuan, an increase of 74% year-on-year.
In the face of adversity, it is the calm tempered by the years and the ambition that never gives up.
Founded in 1988, Luoxin Pharmaceutical ranked among the top 100 enterprises in China's pharmaceutical industry as early as 2006, and now has more than 6,000 employees.
In 2015, we began to lay out P-CAB drugs and carry out differentiated transformation. The listing of Tigorason marks the transformation of Luoxin Pharmaceutical from a leader in the field of generic drugs to a leader in the field of digestion.
Luoxin Pharmaceutical has always had deep roots in the field of digestion, with a revenue of 1.9 billion yuan in digestive system business in 2019, with the previous generation of acid-suppressing mainstream drugs lansoprazole and omeprazole sodium, and in June 2021, the fifth batch of national collection was selected.
Shouldering the heavy responsibility of Ti Gorasheng, it will resolve the impact of collection and consolidation of Luoxin Pharmaceutical's leading position in the field of digestive system.
In order to compete against Takeda Vonorason and sweep the previous generation of PPI drugs, Luoxin Pharmaceutical introduced a trump team of foreign enterprise digestion business to take the helm of marketing.
AstraZeneca's digestive business has always been strong, riding the dust in the PPI drug market, dominating the entire esomeprazole oral drug market.
Lijun Dong is a former Vice President and General Manager of AstraZeneca China's Digestion and Full Product Development Business Unit, with a team of 6,000 people. She was once tasked with promoting the digestion business line to achieve double-digit growth for three consecutive years, making AstraZeneca China back to the first place in the digestion market share. In August 2021, she served as the deputy general manager and chief operating officer of Luoxin Pharmaceutical, strengthening the company's sales ability in the field of digestion, further improving the construction of the direct operation team, and forming a market layout in which the two armies in the core county are parallel, and pharmacies, e-commerce and Internet hospitals are in full bloom.
On April 28, Tigora tablets were officially supplied to major hospitals, Internet hospitals and retail pharmacies across the country. This year, 1,000 hospitalizations and 6,000 pharmacies are expected.
In the field of follow-up digestion, pukanapeptide is expected to become the first approved guanylate cyclase agonist for the treatment of chronic idiopathic constipation in China, with an investment of nearly 100 million yuan in research and development costs, and is currently entering the phase III clinical stage, and is expected to be commercially listed in 2025. The third generation of fish oil-containing three-chamber bag of whole parenteral nutrition Winuf is about to carry out phase III clinical research, suitable for patients who cannot take nutrition through the enteral route, high-dose radiotherapy and chemotherapy malnutrition patients, patients with severe digestive dysfunction, etc. At present, there is no similar product on the market in China, and it is expected to open up new business areas and become a new engine for the company's profit growth.
From the esophagus of the upper gastrointestinal tract, the stomach to the lower gastrointestinal tract and the hepatobiliary pancreas, Luoxin Pharmaceutical will build a full product matrix in the digestive field, bypass the Red Sea, and deepen cultivation in a differentiated field, and will also be quiet for years.