On August 19th, Science and Technology Innovation Board Daily reported (Reporter Xu Hong) that although hypertension is a common disease, its treatment methods are constantly innovating, such as "maintaining one injection for six months" and "minimally invasive surgery in addition to medication".
Among them, RDN therapy has been an important research direction in the field of hypertension treatment in recent years. RDN treatment for hypertension, also known as renal denervation (RDN), is a minimally invasive interventional surgery for treating hypertension that destroys sympathetic nerve fibers in the renal artery wall, thereby reducing sympathetic nerve excitability and lowering blood pressure.
At the end of 2023, the RDN systems of Recor Medical and Medtronic were approved for market by the US FDA, causing a warm response in the industry. After entering 2024, this trend will further sweep across the country.
In April of this year, Medtronic SympCity Spyral RDN was approved by the National Medical Products Administration, becoming the world's first minimally invasive treatment device system for hypertension to be approved for market in three major regions: the United States, the European Union, and China. Following closely behind are local forces, and recently the RDN products of Meili Weiye and Xinmai Medical were also approved on the same day.
However, due to the fact that oral medication has long been used as a traditional treatment for hypertension, the promotion of another new intervention measure often faces many difficulties. After going through a life of nine deaths in research and development, how Medtronic will push the new therapy RDN into clinical practice undoubtedly concerns everyone's attention.
▌ Legendary RDN: The road to market with twists and turns
The development and even market push of a cutting-edge medical technology has never been a straight line, and the launch of the Medtronic Symplicity Spyral RDN is just that.
On November 8, 2023, Recor Medical announced FDA approval for its product Paradise, becoming the first RDN product to be launched in the United States. Nine days later, Medtronic's SympCity Spyral RDN system also received FDA approval for drug treatment of uncontrolled hypertension patients.
This can be called an astonishing reversal. Because just a few months ago, the Symplicity Spyral RDN was rejected at an FDA independent expert group meeting. Although six members voted that the benefits of the system outweighed the risks, more people voted against it.
Although the recommendations of the independent expert group are not binding, the FDA usually refers to the opinions of this advisory group. Why did Symplicity Spyral RDN still receive final approval from the FDA this time? Some analysts believe that this is not unrelated to Medtronic's more than ten years of persistence in developing RDN and accumulating a large amount of clinical data from it.
Medtronic was one of the earliest pioneers to enter the RDN field. As early as November 2010, the company acquired Ardian for $800 million in cash, marking the beginning of the RDN journey.
After completing the acquisition, Medtronic invested heavily in Symplicity research, and two early single arm large-scale studies, HTN-1 and HTN-2, validated the voltage lowering effect of RDN. During this period, the global RDN field also showed a thriving scene, with large-scale mergers and acquisitions and investment and financing being hot, including Medtronic, St. Jude/Abbott, Boston Scientific, ReCor Medical, and many other companies' RDN devices have successively obtained CE certification. The European Society for High Blood Pressure has included RDN in its guidelines.
However, in 2014, the Symplicity HTN-3 trial results released by Medtronic dealt a heavy blow to industry confidence. The experimental data of Symplicity HTN-3 showed that although RDN reduced blood pressure and had good safety, there was no difference compared to the control group.
Since then, not only have companies such as Johnson&Johnson, St. Jude Medical/Abbott, Covidien, etc. stopped developing RDN products, but many medical insurance plans in Europe have also stopped using RDN as a reimbursable treatment method.
But Medtronic did not give up. After a comprehensive analysis of the trial results, Medtronic believes that the failure of the Symplicity HTN-3 trial was caused by multiple reasons, including deficiencies in the design of RDN products and the clinical trial design itself.
Therefore, on one hand, Medtronic has re evaluated its product design approach and changed its product design plan. The first generation device Flex Catheter was a single point catheter, and its usage varied greatly among doctors in terms of placement. The analyzed data showed that most patients were unable to achieve complete ablation.
The updated Spyral device has shifted from one electrode to spiral mode, with four electrodes placed in the 3 o'clock, 6 o'clock, 9 o'clock, and 12 o'clock directions. This design not only makes the system more reproducible and easier to use, but also greatly improves ablation efficiency.
In addition, for the restarted clinical trial project, Medtronic has further improved the clinical design, including paying more attention to patients' use of antihypertensive drugs, tracking drugs in patients' bodies through urine analysis and blood samples, and making every effort to minimize the influence of external variables on the trial results.
Following the SYMPLICITY HTN series research, Medtronic has launched multiple series of studies, including SPYRAL HTN-OFF MED, SPYRAL HTN-ON MED, and Global SYMPLICITY Registry. Among them, the SYMPLICITY Global Registry Study is currently the largest prospective, single arm, global, observational, real-world registry study of RDN, involving over 3000 patients with poor blood pressure control worldwide, aiming to explore the safety and sustainability of RDN efficacy in the real world.
These studies continue to demonstrate the safety, effectiveness, and persistence of RDN, and provide critical scientific evidence for the final approval of Symplicity Spyral RDN in the future.
The FDA independent expert panel debated various reasons, and the last six members voted that the benefits of the system outweighed the risks, but seven members voted against it. The support and opposition votes were actually very close, and the main reason for the expert rejection was that its registered clinical efficacy endpoint was not met
However, in the past few years, Medtronic has conducted extensive clinical trials, and many RDN cases have shown good and sustained treatment outcomes. Therefore, based on multiple considerations, the FDA has approved the marketing of Medtronic SympCity Spyral RDN Liu Zhong (pseudonym), an industry insider who has been keeping an eye on RDN technology for a long time, told reporters.
From research and development to market launch, Medtronic RDN has gone through a long and winding journey. Especially the difficulty of running blood pressure tests is very high, as there are many external variables that can affect blood pressure and the variables are difficult to control. Despite experiencing more than one failure, Medtronic has been able to keep moving forward. In the industry's view, this is more based on its long-term strategic layout considerations and confidence in RDN technology.
Continuous research and clinical trials, persistent innovation and improvement, multi-party cooperation Medtronic believes that the successful listing of Symplicity Spyral RDN is also inseparable from these efforts.
Faced with the research and development challenges of RDN technology, Medtronic continuously explores and implements improvement measures to optimize its products, making them safer and more effective. At the same time, through internal and external multi-party cooperation, the company helps to deeply understand the needs and adapt more quickly to the constantly changing regulatory environment and market situation. "In a written response to the Science and Technology Innovation Board Daily reporter, Medtronic said this.
How to choose surgical treatment for hypertension?
Since there are drugs available, why do hypertensive patients still choose RDN surgery for treatment? In fact, treating hypertension with RDN is like giving a patient a super pill, which only needs to be taken once in their lifetime.
However, this pill is not omnipotent either. Medtronic staff said, "This is because some patients can see clear treatment effects quickly after using it, while others need to continue taking medication after surgery, cooperate with doctors to manage blood pressure throughout the process, or continue to maintain lifestyle changes
RDN is not suitable for all hypertensive patients, it is mainly used as an adjuvant therapy for refractory hypertension and hypertension patients with drug intolerance. Among them, "refractory hypertension" is defined as patients who have been taking three or more antihypertensive drugs (including one diuretic) to treat poor blood pressure control for more than three months; Drug intolerance "refers to patients who are contraindicated with drugs or cannot tolerate medication due to adverse drug reactions.
Therefore, for hypertensive patients who may find it difficult to achieve ideal blood pressure control solely through medication, RDN can be combined with drug therapy as a comprehensive treatment approach to achieve better therapeutic effects. If patients have poor response to hypertension drugs or have drug tolerance issues, RDN also provides an effective alternative solution.
In addition, a large number of clinical trials have shown that the antihypertensive effect of RDN can not only last for a long time, but its operation is relatively simple and its safety is also relatively high
As an innovative technological means and technique, the full launch of Symplicity Spyral RDN still requires a lot of preliminary preparation. But before it was officially approved, this therapy had already been tested in the Boao Pilot Zone in Hainan, and the first patient implantation was completed in April 2021. So far, it has benefited more than 50 Chinese hypertensive patients.
61 year old Aunt Zhang is one of them. For Aunt Zhang, who has been suffering from stubborn hypertension for over 20 years, this surgical experience is truly miraculous: "The whole process was like sleeping without any pain. Then, when she woke up, the pain disappeared
Before undergoing RDN surgery, Aunt Zhang's high blood pressure had developed to a level that was almost uncontrollable even with medication (high blood pressure was about 180-190). If hypertension is not timely and effectively controlled for a long time, it can cause arteriosclerosis, vascular stenosis, and blood supply disorders to various tissues and organs, leading to serious complications of hypertension, especially the damage to the heart, brain, and kidneys.
For so many years, my blood pressure medication has been constantly upgraded, and even after taking several drugs in combination, my blood pressure still cannot be controlled. The doctor said that my situation is already at its limit, and if one more drug fails, there will be no cure. Moreover, I have developed complications of heart disease, the severity of which even exceeds that of hypertension itself. "Aunt Zhang told reporters that the continuously worsening condition has caused great pressure on her body and mind. I am very scared to think that both of my parents passed away due to hypertension and cerebral hemorrhage, and I feel that this situation is also very close to me
After several appointments and waiting, Aunt Zhang completed the RDN surgery at Ruijin Hospital in Boao, Hainan by the end of February 2023. To her surprise, after this surgery, her previously uncontrollable high blood pressure, which was like a wild horse, finally improved.
After the surgery, her blood pressure dropped significantly and is now basically no different from normal people. She has recovered to the normal range of 70-80 for low pressure and 100-120 for high pressure. The antihypertensive drugs she used to take have also been reduced under the guidance of doctors, and so far only one is left.
As the first beneficiary, Aunt Zhang sighed that it was RDN technology that gave her a new lease on life. She said that after no worries about high blood pressure, she felt that all aspects of life were very good. "I can drive my grandson to and from school alone, travel with friends with peace of mind, and enjoy my retirement time.
It is worth mentioning that due to the fact that most hypertensive patients have no symptoms or have symptoms that are not obvious, many people have insufficient awareness of the dangers of hypertension. In fact, hypertension is the most important risk factor for early onset cardiovascular disease, leading to about 54% of global stroke and 47% of ischemic heart disease, such as stroke, coronary heart disease, heart failure, etc., which are common complications. The incidence rate and disability rate of patients are high.
According to relevant data, the current mortality rate of cardiovascular and cerebrovascular diseases in China accounts for 41% of the total mortality rate, with an annual death toll of 3.5 million. Among them, 70% of strokes and 50% of myocardial infarction are related to hypertension.
Liu Zhong believes that the large number of hypertensive patients in China will bring many opportunities for the commercialization of RDN. But the challenge still lies in how to make patients accept this intervention therapy in their minds like Aunt Zhang. In addition, surgical costs priced at or above 100000 yuan are a significant threshold for many patients, so there may still be a long way to go in the future.