FDA Rejects Melatonin Agonist Hetlioz for Insomnia; Merck's Once-Weekly HIV Therapy Shows Promise; Aspirin Enteric-Coated Tablets Likely Included in National Volume-Based Procurement

A Total of 5 Briefs | Estimated Reading Time: 5 Minutes◆◆ ◆

01

FDA Rejects Approval of Melatonin Receptor Agonist Hetlioz for Insomnia Indication

On March 6, Vanda Pharmaceuticals announced that it had received a Complete Response Letter from the FDA regarding the Hetlioz (tasimelteon) supplemental New Drug Application (sNDA) for the treatment of insomnia.

FDA stated that defects beyond the labeling and post-marketing requirements/commitments were found, and the current sNDA cannot be approved. Vanda is currently reviewing it and assessing the next steps.

Hetlioz is a melatonin receptor agonist that was approved in the U.S. in January 2014 for the treatment of Non-24-Hour Sleep-Wake Disorder. In December 2020, the product received FDA approval for a new indication to treat sleep disturbances in Smith-Magenis Syndrome (SMS).

According to the company's financial report, Hetlioz achieved full-year sales of $100.2 million in 2023, representing a 37% decrease compared to $159.7 million in 2022, primarily due to intensified competition from generic drugs.

Source: PharmaCube

02

Johnson & Johnson's "Guselkumab" Granted Priority Review for Crohn's Disease

On March 6, according to the CDE official website, Johnson & Johnson's submission of Guselkumab Injection is proposed to be included in the priority review for the treatment of adult patients with moderately to severely active Crohn's disease (CD).

Source: CDE Official Website

In July 2017, the FDA approved Guselkumab Injection for the treatment of adult patients with moderate to severe plaque psoriasis, making it the world's first monoclonal antibody targeting human interleukin-23 (IL-23) approved for psoriasis treatment. Since then, it has actively expanded into other indications. It has now been approved for multiple indications in various regions, including the United States and Japan, covering conditions such as palmoplantar pustulosis and psoriatic arthritis.

In China, the first approval time of Guselkumab was December 2019, for adult patients with moderate to severe plaque psoriasis suitable for systemic treatment.

For Crohn's disease, a Phase III and a Phase II/III clinical study are currently being conducted in regions including mainland China. In May 2022, Johnson & Johnson disclosed the results of the Phase II GALAXI trial of Guselimumab for the treatment of moderate to severe active Crohn's disease.

The study enrolled Crohn's disease patients who had an inadequate response or were intolerant to conventional therapies or biologics. The trial results showed that in different patient cohorts receiving various doses of guselkumab, the proportion of patients achieving clinical-biomarker response at 48 weeks was 47.5% to 66.7%; the proportion of patients achieving endoscopic remission was 44.3% to 46%; and the proportion of patients achieving clinical remission with normalized C-reactive protein or fecal calprotectin levels was 39.3% to 66.7%.

In addition to Crohn's disease, there are currently two Phase III clinical studies for ulcerative colitis being conducted in China (Registration numbers: CTR20223406; CTR20234114).

Source: Insight Database

03

New Type 1 Traditional Chinese Medicine Arrives! Ripples in a 54 Billion USD Market

Recently, the CDE official website showed that the traditional Chinese medicine (TCM) 1.1 class new drug Qishen Granules, submitted by Beijing Tong Ren Tang, has obtained clinical trial tacit approval for the treatment of chronic heart failure with symptoms of qi deficiency and blood stasis. Data from Menet shows that in 2022, the market size of cardiovascular disease TCMs in China's three major terminals and six major markets (the statistical scope is detailed at the end of this article) exceeded 54 billion yuan.

The new Class 1.1 traditional Chinese medicine, Qishen Granules, has the efficacy of replenishing qi, warming yang, activating blood circulation, and detoxifying. It is suitable for chronic heart failure with qi deficiency and blood stasis syndrome, presenting symptoms such as chest pain, chest tightness, palpitations, shortness of breath, fatigue, and a pale purple tongue. The clinical application of this product was accepted by the CDE on December 20, 2023, and received implied permission for clinical trials on March 4, 2024.

Data from Menet shows that in recent years, the market size of traditional Chinese medicine for cardiovascular diseases in China's three major terminals and six major markets has fluctuated but has remained above 54 billion yuan. In the first half of 2023, its sales exceeded 30 billion yuan. From the perspective of terminal sales, the in-hospital market (public hospitals + public primary healthcare) is its main sales channel.

Sales of Cardiovascular Disease Traditional Chinese Medicine in China's Three Major Terminals and Six Markets in Recent Years (Unit: Ten Thousand Yuan)

Source: MiNei Network Pattern Database

In the first half of 2023, the sales of the top five brands of traditional Chinese medicine for cardiovascular diseases in the hospital market all exceeded 1 billion yuan, and all showed positive year-on-year growth. Among them, Tasly's Compound Danshen Dripping Pills ranked first, with sales exceeding 1.5 billion yuan; the sales growth rates of Buchang Pharmaceutical's Wenxin Granules and Yiling Pharmaceutical's Shensong Yangxin Capsules both reached double digits.

Top 5 Brands of Cardiovascular Disease Traditional Chinese Medicine in China Public Medical Institutions Terminal 2023H1

Source: Terminal Competition Pattern of Pharmaceutical Products in China's Public Medical Institutions (MiNe Network)

In the research and development of new traditional Chinese medicine for cardiovascular and cerebrovascular diseases, since 2023, two Class 1 new drugs have been submitted for NDA in China (excluding non-formulation products): Yuelon Pharmaceutical's Tongluo Jiannao Tablets and Hydroxysafflor Yellow A for Injection; two Class 1 new drugs have been approved for clinical trials, both for cardiovascular disease medications, including Beijing Tongrentang's Qishen Granules and Kangyuan Pharmaceutical's Wuwei Yixin Granules.

Some Class 1 New Cardiovascular and Cerebrovascular Traditional Chinese Medicine Drugs Applied for Since 2023

Source: MiNeiNet China Application Progress (MED) Database

Cardio-cerebrovascular diseases are a key area of expertise for Beijing Tong Ren Tang. The company currently holds production licenses for more than 60 traditional Chinese medicines in this category, including classic products such as Angong Niuhuang Pill, Tong Ren Niuhuang Qingxin Pills, and Tong Ren Dahuo Luo Pills. Data from Menet shows that the sales of Beijing Tong Ren Tang’s Angong Niuhuang Pill in physical pharmacies across Chinese cities totaled over 1.6 billion yuan in the first half of 2023.

Source: Menet

04

Expected to Become the First, Once-a-Week Long-Acting HIV Therapy for Long-Term Viral Suppression

Gilead Sciences and MSD announced today the latest results of a phase 2 clinical trial for the long-acting HIV oral combination therapy islatravir and lenacapavir. The results showed that at 24 weeks, this innovative combination maintained a high rate (94.2%) of viral suppression (HIV-1 RNA <50 copies/mL) in HIV patients. The press release noted that the trial results indicate this innovative combination has the potential to become the first once-weekly oral HIV combination therapy. Single-tablet daily oral therapies have already transformed HIV treatment, and reducing dosing frequency may address some of the adherence, stigma, and other challenges faced by individuals taking daily oral antiretroviral therapy.

In this open-label, active-controlled phase 2 study, adult patients who were taking Biktarvy and had suppressed viral levels were randomly assigned in a 1:1 ratio to receive either weekly oral islatravir and lenacapavir (n=52) or continue daily oral Biktarvy (n=52).

The primary endpoint result was the number of patients with HIV-1 RNA ≥50 copies/mL at Week 24. The data showed that one participant (1.9%) receiving islatravir and lenacapavir had viral levels exceeding 50 copies/mL at Week 24; this participant’s viral levels were suppressed by Week 30. In the Biktarvy group, no participants had viral levels exceeding 50 copies/mL at Week 24. The secondary endpoint was the proportion of individuals with HIV-1 RNA < 50 copies/mL at Week 24, and the results showed that participants who switched to once-weekly islatravir and lenacapavir treatment or continued on Biktarvy maintained a comparably high HIV suppression rate at Week 24 (94.2% vs. 94.2%).

In terms of safety, grade 1 and 2 treatment-related adverse events (TRAEs) reported in the islatravir and lenacapavir groups included dry mouth and nausea (each 3.8%). No grade 1 or 2 TRAEs were reported in the Biktarvy group. No grade 3 or 4 TRAEs related to the study drugs were reported in either treatment group. This Phase 2 clinical trial will continue in an open-label manner until Week 48. Long-term data will be presented at future scientific conferences.

Lenacapavir (brand name Sunlenca) is a "first-in-class" long-acting HIV capsid inhibitor, suitable for combination therapy with other antiretroviral drugs to treat multidrug-resistant HIV infections in adult patients. It has received regulatory approval in multiple countries and regions. Islatravir (MK-8591) is a nucleoside reverse transcriptase translocation inhibitor under evaluation by Merck, intended for use in combination with other antiretroviral drugs for the treatment of HIV-1.

Source: WuXi AppTec

05

This Drug with Annual Sales Over 3.2 Billion Yuan May "Not Escape" the Tenth Round of Centralized Procurement

Recently, the National Medical Products Administration released information on the delivery of drug approval certificates, including the approval of multiple product specifications such as the aspirin enteric-coated tablets developed by Nanjing Daoqun Pharmaceutical Co., Ltd.

Source: National Medical Products Administration

In addition, 10 companies including Renhe Yikang, Jilin Sihuan Pharmaceutical, and Jiangsu Biyee Biotechnology have submitted generic applications for aspirin enteric-coated tablets, all of which are currently under review and approval.

Annual sales exceed 3.2 billion, already meeting the "threshold" for centralized procurement eligibility.

As a commonly used drug for antithrombotic treatment and prevention, aspirin enteric-coated tablets have not yet been included in the national centralized procurement. However, around 10 companies, including Jiangsu Wango Pharmaceutical, Chenxin Pharmaceutical, Lepu Hengjiuyuan Pharmaceutical, Chongqing Youyou Pharmaceutical, Nanjing Daoqun Pharmaceutical, Yantai Luyin Pharmaceutical, Guilin Pharma, Shijiazhuang Ouyi Pharmaceutical, and Zhejiang Jingxin Pharmaceutical, have already met the "threshold" for inclusion in the centralized procurement.

In fact, there are already more than 200 companies in China that have obtained production approval for enteric-coated aspirin tablets. In the Chinese aspirin market, Bayer holds a dominant position. According to data from CKDM (China Key Drug Monitoring), in recent years, the annual sales of enteric-coated aspirin tablets in hospitals of all levels across China have exceeded 1 billion yuan. Specifically, in 2022, hospital sales reached 1.538 billion yuan, with Bayer accounting for 95.79% of the market share; retail channel sales in 2022 were 1.685 billion yuan, with Bayer occupying 70% of the market share; total sales in hospitals and retail markets in 2022 exceeded 3.2 billion yuan.

Sales of Aspirin Enteric-Coated Tablets in Hospitals Across China

Source: Sino Health Kaisi System

Sales of Aspirin Enteric-Coated Tablets at Retail Outlets Across China

Source: Sino Health Care System

Aspirin, known as one of the three classic drugs in the history of medicine, is the world's most widely recognized antipyretic, analgesic, and anti-inflammatory drug. However, this century-old "wonder drug" has taken a long time to make its way into centralized procurement in China, and even today it has not been officially included. Only a few products, such as Aspirin Enteric-coated Tablets by Jinan Yongning Pharmaceutical, Aspirin Enteric-coated Tablets by Shenyang Aojina Pharmaceutical, and Aspirin Sustained-release Tablets by Zhengzhou Xiehe Pharmaceutical Factory, have been selected in local centralized procurement.

Since Hoffmann first successfully prepared it in 1897, the research and development history of aspirin has been over a hundred years. However, the extremely challenging production process and stability of enteric-coated aspirin tablets once made many pharmaceutical companies hesitate to proceed. Since the consistency evaluation was launched in 2015, it wasn't until early 2020 that a company in China first submitted an application. It was not until 2021 that Chenxin Pharmaceutical became the first company to pass the consistency evaluation.

Source: National Medical Products Administration

China’s 330 Million Cardiovascular Disease Patients Represent an Antithrombotic Drug Market Exceeding 30 Billion.

With the development of China's aging population and the influence of high-risk factors such as hypertension, hyperlipidemia, and hyperglycemia, the incidence and mortality of thrombotic diseases are on the rise. According to the results of the third national survey on causes of death, cerebrovascular diseases account for 22.45% of total deaths in China, with 2.5 million new stroke cases occurring annually.

Data released by the National Cardiovascular Center of China in the "Report on Cardiovascular Health and Diseases in China 2022" shows that there are currently about 330 million cardiovascular disease patients in China, with the market size for antithrombotic drugs exceeding 30 billion yuan. As a commonly used medication for middle-aged and elderly individuals, aspirin enteric-coated tablets are widely used in clinical practice and play an important role in the treatment and prevention of cardiovascular and cerebrovascular diseases.

Previous media reports indicated that for healthy young and middle-aged populations, the aspirin enteric-coated tablets that passed the consistency evaluation showed bioequivalence in terms of absorption rate and extent compared to those that did not pass the evaluation. However, for middle-aged and elderly populations, there were still significant differences in bioequivalence.

Currently, aspirin has shown its research value in various fields such as cancer prevention, blood sugar reduction, anti-aging, and Alzheimer's disease. Data from the analysis of the current status of the aspirin industry indicates that traditional areas like cardiovascular and cerebrovascular diseases, pain management, and thrombosis remain the mainstream focus of research. However, new directions, including aspirin's role in lung cancer and type 2 diabetes, are also emerging.

Source: Xinkangjie

Editor: Ren Luyun

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