Kekai Life Sciences Completes Full Acquisition of Shanghai Fangwei Medical to Advance Mitral Valve Repair Systems into Large-Scale Clinical Trials

VCBeat (WeChat ID: vcbeat) has learned that on July 17, Kokai Life Sciences, a technology company dedicated to the R&D of interventional heart valve devices, recently completed the full acquisition of Shanghai Fangwei Medical Technology Co., Ltd. Founded in 2019, Fangwei Medical is an innovative company primarily focused on developing mitral annuloplasty products. This acquisition will further accelerate Kokai Life Sciences’ growth and enhance its product portfolio, enabling it to benefit more patients with a more specialized range of offerings.

Kokai Life Sciences, established in 2018, has set up its product R&D center in Shanghai Zhangjiang Science City. The company is composed of domestic and international teams with extensive experience in heart valve development. Leveraging core platform technologies such as integrated precision machining, medical-grade polymer membrane materials, and hemodynamics, Kokai Life Sciences is building a human valve repair system. Starting with mitral and tricuspid valve repair systems, the company provides systematic solutions for valvular diseases tailored to different populations, needs, and clinical scenarios. Its mitral valve repair system, SuperClip, has completed design, development, and animal studies, and is preparing to launch large-scale clinical trials. Meanwhile, other pipeline products, including the FlexClip mitral valve repair system and the FlexClamp tricuspid valve repair system, have also completed their R&D phases and are currently undergoing extensive preclinical studies. To enhance the completeness and leadership of its product portfolio in the field of valve repair, Kokai Life Sciences has decided to enter the area of mitral annuloplasty.

According to a population-based study conducted by the Mayo Clinic in the United States, the incidence of various valvular heart diseases increases with age. Among these, mitral regurgitation has a significantly higher incidence than aortic stenosis, aortic regurgitation, and mitral stenosis. The incidence of mitral regurgitation is 6.4% in individuals aged 65–74 years and rises to 9.3% in those aged 75 years and older. A survey conducted by Fuwai Hospital of the National Center for Cardiovascular Diseases among individuals aged 35 years and older also found that the incidence of mitral regurgitation is positively correlated with age. The advent of an aging society has led to a continuous increase in the proportion of the population aged 65 years and older in China. This proportion rose from 8.34% in 2003 to 11.94% in 2018 and is projected to reach 17.22% by 2035. With the population aged 65 years and older in China expected to exceed 250 million, and assuming a 10% incidence rate for moderate-to-severe mitral regurgitation, the total number of patients with mitral regurgitation will surpass 25 million.

The etiologies of mitral regurgitation are primarily categorized into two major types: primary and secondary (also known as functional). Primary lesions refer to valvular insufficiency caused by structural and functional abnormalities of the mitral valve itself, including degenerative disease, papillary muscle dysfunction, infective endocarditis, and rheumatic heart disease. Secondary lesions refer to regurgitation resulting from mitral annular dilation due to left ventricular dysfunction associated with ischemic heart disease and other cardiomyopathies. A study based on an echocardiographic database at Zhongshan Hospital indicated that primary and secondary lesions each accounted for 50% of patients with severe mitral regurgitation, with degenerative disease comprising 63% of the primary cases [4].

Currently, the aging society has led to a large population of patients with mitral valve disease. The surgical treatment for mitral valve disease is gradually shifting from open-heart surgery to minimally invasive and interventional therapies. The promotion of minimally invasive procedures is expected to improve patient acceptance of mitral valve surgery, while interventional therapies with broader indications and less invasiveness will become the future trend.

Interventional treatment options for mitral valve disease include transcatheter mitral valve repair (TMVr) and transcatheter mitral valve replacement (TMVR). Mitral valve repair can be further categorized into three types: edge-to-edge repair, annuloplasty, and artificial chordae tendineae implantation. The two primary access routes are the transfemoral venous approach and the transapical approach via a minimal surgical incision.

Transcatheter interventional valve repair and replacement procedures offer significant advantages over conventional surgical approaches, characterized by minimal invasiveness, and represent a crucial therapeutic option for patients who are not candidates for open-heart surgery. Among these interventions, repair is generally preferred over replacement when feasible. Both domestic and international medical companies are optimistic about the market potential, leading to a proliferation of new products. Comparative results from clinical trials have become focal points of discussion at various medical conferences and among key opinion leaders in the field, with particular attention paid to relevant indications and the comparative merits and drawbacks of different products. In summary, edge-to-edge repair is effective for bileaflet prolapse, applicable to both primary and secondary cases, and offers a high safety profile, although its long-term durability is limited. Artificial chordae tendineae implantation is indicated only for patients with primary posterior leaflet prolapse and chordal rupture, thus having narrow indications. Annuloplasty is primarily used for secondary mitral regurgitation and can be combined with leaflet repair to stabilize the annulus; however, current transcatheter fixation methods predominantly rely on anchor-based systems, which carry a risk of causing myocardial injury.

Compared with edge-to-edge repair, annuloplasty does not damage the valve leaflets. Furthermore, unlike artificial chordae implantation, which is applied to patients with primary mitral regurgitation, annuloplasty is primarily indicated for patients with functional and secondary mitral regurgitation. This represents the advantage of annuloplasty over the other two techniques.

Transcatheter Mitral Annuloplasty can be categorized into two main types: direct annuloplasty and indirect annuloplasty. Direct annuloplasty commonly involves the catheter-based placement of an adjustable artificial annuloplasty band at the mitral annulus to reduce its diameter for therapeutic purposes. In contrast, indirect annuloplasty achieves therapeutic goals by implanting a device via the coronary sinus to encircle and constrict the annulus. However, due to frequent anatomical variations among the coronary sinus, the mitral annulus, and the left circumflex coronary artery, the application of indirect annuloplasty remains relatively limited.

There are numerous mitral annuloplasty products available internationally, yet few companies in China are known to be developing such devices. Currently, the publicly disclosed mitral annuloplasty products from overseas mainly come from the following five companies:

• Edwards’ Cardioband annuloplasty system is classified as a direct annuloplasty device. It received CE marking in 2015. Clinical trials have demonstrated an implantation success rate approaching 100%, with a 30-day mortality rate below 5%. Following implantation, the mitral annulus exhibited significant reduction, mitral regurgitation was markedly alleviated, and cardiac function showed substantial improvement that was sustained for two years.

• Mitralign, Inc.’s Mitralign annuloplasty system is classified as a direct annuloplasty device. It received CE marking in February 2016. Published clinical data demonstrate low 30-day all-cause mortality and adverse event rates with this repair system, along with reduced mitral regurgitation severity and improved cardiac functional class, thereby confirming its safety and efficacy.

• Cardiac Dimensions’ Carillon, an indirect annuloplasty system, received CE marking in January 2009 and had completed 1,000 implantations by July 1, 2019. According to currently available clinical data, the device significantly improved regurgitation in patients with functional mitral regurgitation (MR), showed no significant difference in adverse event rates compared to the control group, and significantly reduced hospitalizations for heart failure.

• Boston Scientific’s acquisition of Millipede, Inc.’s Iris annuloplasty ring marks the first complete annuloplasty ring designed for transcatheter implantation. Compared with other “semi-ring” devices (such as Cardioband), it may offer a lower rate of recurrent mitral regurgitation post-implantation. Furthermore, it can be used in conjunction with leaflet repair devices (such as MitraClip) to stabilize the annulus, thereby prolonging the durability of the repair effect.

• Additionally, the AccuCinch transcatheter ventricular repair system, the first of its kind developed by Ancora Heart, a medical device company based in California, USA, for treating heart failure caused by left ventricular dysfunction as well as functional mitral regurgitation, and the Amend transcatheter mitral valve repair system developed by an Israeli medical device company, both mimic the annuloplasty rings most commonly used in current surgical procedures.

According to Kokai Life Sciences, the key design considerations for annuloplasty systems primarily involve configuration (semi-ring or complete D-shaped ring), fixation location (supra-annular or sub-annular), and fixation method (rivets or other techniques). Overcoming the technical challenges of annuloplasty, reducing the procedural complexity and minimizing damage to the myocardium and other tissues, developing more effective and superior mitral annuloplasty products, and establishing a more specialized product portfolio to benefit patients with diverse clinical presentations are all directions in which this innovative company must continuously strive.

Finally, Kokai Life Sciences stated that professional depth determines future height, while product variety determines market breadth. The mutual reinforcement and compounding of resources can generate a multiplier effect, enabling the company to meet the needs of patients with different indications and to expand and refine the valve market. Producing differentiated, high-quality valve products to save patients' lives and improve their quality of life is the goal and pursuit of Kokai Life Sciences.

Note: Some content sourced from:

Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. Burden of valvular heart diseases:a population-based study.Lancet，2006;368:1005–1011.

Nie Jingyu, Wang Zengwu, Zhang Linfeng, et al. Study on the current status of mitral regurgitation and its influencing factors in population aged 35 years and older. Chinese Circulation Journal, 2017, 32: 475.

China Statistical Yearbook (2003–2019): China Statistics Press.

.Jianmin Li, Wenzhi Pan, Yigang Yin, Leilei Cheng & Xianhong Shu .Prevalence and correlates of mitral regurgitation in the current era: an echocardiography study of a Chinese patient population, Acta Cardiologica,2016;71:1, 55-60.