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Condensing the process of developing and launching a new drug with a breakthrough mission, there's always a thrilling sense of excitement, like hearing thunder in the silence.

In 2014, Academician Zhong Nanshan of the Chinese Academy of Engineering initiated a clinical research project on tobramycin inhalation solution. The reason for launching this project was the increasing incidence of bronchiectasis in China, coupled with a lack of clinical guidelines and relevant antibacterial drugs with indications in the country.

The fact that a leading figure in the Chinese respiratory medicine field values tobramycin so highly shows that this commonly used antibiotic is not so ordinary; perhaps it's just a matter of "how to use it".

In fact, this project aimed to achieve a historic breakthrough.

Therefore, the scientific research and development of tobramycin inhalation solution was included in the national "Major New Drug Creation" special support catalog and was led by Professor Guan Weijie of the National Clinical Medical Research Center for Respiratory Diseases, Guangzhou Respiratory Research Institute, and other top scholars.

On October 11, 2022, eight years after the project was initiated, tobramycin inhalation solution was finally approved for marketing and given its brand name—Jianketo®.

For the creators of Jianketo®, the listed company Health Yuan (600380.SH) will undoubtedly enter another wave of commercial harvest period.

But more importantly, through a virtuous cycle of industry, academia, research, and investment resonance, Health Yuan, which has been steadily developing in the field of inhalation preparations, while striving to improve the accessibility of medicines for the public, is beginning to strive for more world-class peaks.

1 | Breakthrough

The Significance of Listing

"The prevalence of bronchiectasis (BE) in China is 1.2%" This is a frequently cited statistic from domestic research institutions and media. In fact, no large-scale epidemiological survey of BE has been conducted in China to date.

This 1.2% prevalence data is merely the result of a telephone survey conducted in 2013 among residents aged 40 and above in seven urban areas: 135 out of 10,811 respondents had been diagnosed with BE.

The sample size and distribution are clearly insufficient to reflect statistically significant results, but based on this, it is not difficult to conclude that the actual prevalence of BE in China should be higher than 1.2%.

In any case, with a large population of 1.4 billion, even 1.2% represents nearly 17 million patients. Moreover, epidemiological data from abroad show that the incidence and prevalence of BE have been steadily increasing.

Although bronchiectasis is a common chronic respiratory disease, clinical attention mainly focuses on the treatment of acute exacerbations, with a lack of effective management of stable-stage bronchiectasis, leading to easy recurrence.

From a doctor's perspective, many domestic clinical guidelines for bronchiectasis are based on foreign guidelines or consensus. A practical problem is the lack of accessible drugs for doctors to use in clinical treatment.

In the past 15 years, nine guidelines/consensus have been published abroad, while China published its first version of the "Expert Consensus on Diagnosis and Treatment of Bronchiectasis in Adults" in 2012, which greatly promoted the standardized diagnosis and treatment of bronchiectasis.

In order to accumulate more clinical research data and address issues such as lack of guidelines and drug accessibility, Academician Zhong Nanshan promoted the project research on tobramycin inhalation solution, and Chairman Qu Jieming (President of Ruijin Hospital, Shanghai) led the establishment of the China Bronchiectasis Alliance.

Therefore, The R&D process of Jianketo®, can be considered as part of the medical community's systematic understanding of bronchiectasis and the search for solutions.

In April 2021, a new version of the "Expert Consensus on Diagnosis and Treatment of Bronchiectasis in Chinese Adults", compiled by dozens of experts under the auspices of the Infectious Disease Group of the Respiratory Diseases Branch of the Chinese Medical Association, was officially released.

The new consensus divides bronchiectasis into acute and stable phases and classifies patients according to their phase and whether they have bacterial colonization in the respiratory tract.

These classifications allow clinicians to better select drugs. In the clinical treatment of stable-stage bronchiectasis patients, the expert consensus clearly encourages the long-term use of inhaled antibiotics.

Returning to the birth of Jianketo®, from the day the project was initiated, it was given greater expectations, which is not merely the result of the "blessing" of Academician Zhong Nanshan and other big names.

In the past, long-term use of oral or injection methods in the clinical treatment of bronchiectasis had significant side effects and easily led to drug resistance. Therefore, Jianketo® is one of the research choices that balances these problems.

In fact, many previous clinical studies on bronchiectasis have ended in failure. At the beginning of the development of Jianketo®, Health Yuan also faced many uncertainties, but after 8 years of persistence, it finally bore fruit.

Successful approval, Jianketo® has achieved an important breakthrough in the field of respiratory diseases in China, filling the gap in inhaled treatment for bronchiectasis patients in China and providing accessible tools for the standardized clinical management of stable-stage patients.

Looking back at the R&D process of Jianketo®, a large number of academic and research resources were used.

It was Academician Zhong Nanshan, as the academic leader, who mobilized more than 40 clinical centers, eventually enrolling 32 centers, screening 594 cases, and recruiting 357 cases for the tobramycin inhalation solution.

During the more than four years of clinical trials, Academician Zhong personally presided over the world's first double-blind clinical efficacy study, and obtained significant positive efficacy characteristics conclusions, obtaining reliable data support for the registration and listing of Jianketo®.

2 | Change

Evolving Drug Delivery Methods

The key reason why Jianketo® is a groundbreaking new drug is that it changes the drug delivery method for bronchiectasis.

支扩症患者中，大多会感染一种叫铜绿假单细胞菌的条件致病菌。面对支扩患者，医生都很清楚，解决掉这种喜欢定植在呼吸道的细菌，是治疗的关键一环。

然而，人类与致病细菌的斗争史却又是一个宏大而冗长的故事。

在临床医学实践中，由于长期应用抗生素，虽然大多数的敏感菌株不断被消灭，但同时耐药菌株却能大量繁殖，使得药物作用力明显降低。

针对广泛存在于自然界中，人类很容易接触和感染到的铜绿假单细胞菌，也不是没有抗生素药物，只是因为耐药性的问题，造成了长久以来用药可及性成为难题之一。

不仅是支扩症。由于铜绿假单细胞菌是医院环境中最主要感染的病原菌种，患有代谢性疾病、血液病、恶性肿瘤的患者，以及术后或某些治疗后的患者也非常容易感染，从而造成医疗系统和患者的成本增加。

所以首先是要找出临床耐药性较低的抗生素，并加以改进，使之在用药过程中尽可能降低细菌耐药反应产生。

钟南山院士提出妥布霉素吸入溶液的临床研究，正是考虑到妥布霉素耐药性较小的特点，同时吸入溶液也意味着给药方式上有所不同。

不要小看给药方式的改变。通过局部给药会比传统的静脉注射给药浓度提升百余倍，如此既能做到治疗细菌感染，又会减少耐药菌的产生。

“我们对新型抗菌药物的使用走过一段弯路。早在四十年前，国内很多医生就尝试用抗菌药物进行支扩症的治疗，但都是以静脉注射为主的给药方式，这是不合理的。”

深圳呼吸疾病研究所所长陈荣昌教授认为，吸入制剂是治疗呼吸系统疾病首选给药的途径。

这也是业界的一种共识，但过去吸入制剂装置真正带入肺部的药物比例较低，成为一大用药障碍。也因此，吸入制剂没少遭质疑。

既然是突破性的吸入抗生素，健可妥®必定要做出有效的改变。

一方面是药物研发上，将妥布霉素的颗粒度调理到更适用于吸入气道；另一方面则是改进吸入装置，特别研发震荡摩塞孔的新型雾化器，使妥布霉素在肺内的沉积量明显提高。

健康元首席科学家金方博士所言健可妥®在这两个方面的改变，听上去简单，但要做到不引起气道刺激、不引起明显的副作用反应，还要把药物真正带到肺部，实际是很难的一件事。

健康元首席科学家金方博士

吸入制剂其实属于技术含量很高的复杂制剂，国际市场上，阿斯利康、葛兰素史克、勃林格殷格翰等跨国药企长期技术垄断。

“过去慢性气道疾病，比如支气管扩张、慢阻肺、哮喘等，首选给药途径就是经气道内吸入，但这些药物基本只能依赖于进口，现在我们很自豪于给药技术途径实现了国产化，能以更亲民的价格造福更多患者。”

与所有临床医生一样，陈荣昌教授非常乐见在对抗病毒、对抗感染真菌上，能不断有新武器出现，有效且成本更低地救助患者。

对于健可妥®的诞生，陈荣昌教授也给出来极高的评价： 这是十年以来我们在支扩症局部治疗上取得的一个很重要的进展。

未来健可妥®进入医保，覆盖更多患者人群，金方博士认为大有希望，因为从国内支扩的诱导因素看，大部分患者是生活质量较低的人群。

在“缺药”的情况下，健可妥®让医生、患者和支付方，都看到了希望已经开始兑现。

叁| 龙头

浓缩突破的价值

每一种新药的诞生、每一种新疗法的开创，都是我们对于疾病认知的一个过程。这个过程，又将激励整个中国创新药行业和企业，奋马扬鞭。

健可妥®的价值兑现，还有一层就是要取得商业成功和资本市场的认同。毕竟健康元是一家上市公司，还关乎着10万投资者的投资利益。

相比吸入疫苗给康希诺带来股价飙涨，吸入抗生素虽然没能给健康元股价来上一针“肾上腺素”，但这并不意味着健可妥®不会在资本市场释放价值。

毕竟对于绝大部分疾病种类和药物研发，一般投资者甚至机构投资者不太可能有相对专业的分析，从而做出投资决策。但通过一些信息和逻辑推导，投资者仍然能够去发现一些其中的真正价值。

回到健可妥®背后的健康元，这家老牌上市公司对市场趋势总有着敏锐的判断，总能做出前瞻性布局，以留给其在关键阶段上做出调整的余地，从而增长的可持续。

实际上，健可妥®对于健康元而言是一个标志性的创新药物，其重要意义就是夯实公司在国内高端吸入制剂市场的领先优势。

十余年前，健康元董事长朱保国便做出重点布局吸入制剂赛道的决定，尤其是在2014年引入金方博士团队后，健康元在国内高端吸入制剂领域的优势加速提升。

截至目前， 健康元已经有7个品种、11个品规的吸入制剂上市，同时还有30余个产品在研。如此丰富的管线产品布局，也是“国产吸入制剂赛道领航者”的底气所在。

“国产吸入制剂赛道领航者”加速商业化兑现

In the domestic market alone, respiratory diseases are the third leading cause of chronic disease mortality, after cardiovascular diseases and tumors. This area has been almost entirely controlled by multinational pharmaceutical companies.

AstraZeneca's budesonide suspension alone generated 7.2 billion RMB in revenue in 2018, making it a truly super-selling product.

According to PDB database data, in 2020, AstraZeneca's inhaled budesonide suspension accounted for 95.19% of sales in domestic sample hospitals.

However, With the participation of domestic pharmaceutical companies such as Healthspring and Zhengda Tianqing in this blockbuster product, "domestic substitution" has become the main trend.

Last June, three drugs for obstructive airway diseases were included in the fifth batch of national centralized procurement. Healthspring's inhaled budesonide suspension, inhaled ipratropium bromide solution, and combined inhaled ipratropium bromide solution all won bids.

The effect of winning national centralized procurement bids was immediate. Healthspring's inhaled budesonide suspension achieved a growth rate of 13066% in key provincial and municipal public hospitals in 2021, and 2420% in the first quarter of this year.

In 2019, the domestic terminal sales scale of budesonide suspension was 8 billion yuan. Since then, only four companies, including Healthspring, have had this product included in centralized procurement, so Healthspring's budesonide suspension is still in the stage of volume expansion.

From the perspective of listed company financial reports, In 2021, inhaled preparations contributed 577 million yuan to Healthspring's annual revenue, a year-on-year increase of 658%. This is considered by securities research institutions as a signal of Healthspring's accelerated commercialization of respiratory preparations.

This year, on the same day that inhaled tobramycin inhalation solution was approved, Healthspring also obtained approval for another new drug for respiratory diseases with excessive thick and viscous mucus secretion—inhaled acetylcysteine solution.

This is another market with domestic terminal sales exceeding 2 billion RMB (2.353 billion RMB according to IQVIA 2021 data). While multinational pharmaceutical companies still dominate the market, Healthspring has opened up another area for domestic substitution.

Having now secured levalbuterol inhalation solution, budesonide inhalation suspension, tobramycin inhalation solution, and acetylcysteine inhalation solution, Healthspring has comprehensively covered six major asthma and COPD treatment drugs.

Looking at Healthspring's R&D pipeline for respiratory disease drugs, a number of new products will enter the late stages of clinical trials in the next few years, and the product lineup will continue to thicken, strengthening its offensive in the market.

Healthspring is only just beginning to unleash the value benefits of being a "leading domestic inhaled preparation player".