Edaptus (Optune) Included in Hangzhou Citizen Insurance as Breakthrough Therapy for Glioblastoma

At the end of last month, Hangzhou launched the affordable insurance product “Hangzhou Citizen Insurance,” offering supplemental medical coverage to enrollees in Zhejiang Provincial Employee Basic Medical Insurance and Hangzhou Municipal Basic Medical Insurance for an annual premium of 59 yuan.

According to the “Coverage Plan” of Hangzhou Citizen Insurance, for inpatient medical expenses incurred by insured persons at designated medical insurance hospitals, the out-of-pocket portion remaining after basic medical insurance reimbursement, as well as eligible drug expenses covered under the “Hangzhou Citizen Insurance Specific High-Cost Drug List” incurred at designated medical insurance hospitals of Tier II or above, shall be reimbursed at 75% by Hangzhou Citizen Insurance after deducting separate annual deductibles of RMB 20,000 and RMB 0, respectively.

VCBeat noted that the Hangzhou Citizen Insurance List of Specific High-Cost Drugs, released concurrently, includes not only immunotherapies and targeted oncology drugs such as Keytruda, Tagrisso, and Rozlytrek, but also a tumor treating fields (TTFields) therapy marketed under the brand name “AiPuDun.” According to coverage restrictions, AiPuDun is indicated solely for adult patients with histologically confirmed glioblastoma multiforme (GBM). It is understood that the use of AiPuDun involves the Optune device and disposable transducer arrays. Patients can apply for complimentary use of the device through DTP (Direct-to-Patient) pharmacies, while the disposable transducer arrays are purchased out-of-pocket on a monthly basis.

Based on a unit price of RMB 3,324.95 per patch and a replacement frequency of every 3–4 days, the monthly consumption amounts to approximately 40 patches, resulting in a monthly treatment cost for Aipudun exceeding RMB 130,000. Clinical observations indicate that Aipudun therapy must be sustained for at least six months, leading to a total cost of nearly RMB 800,000. However, if patients successfully obtain reimbursement for specific high-cost drugs under the Hangzhou Citizen Supplementary Medical Insurance (Hangzhou Shiminbao), the total cost of Aipudun treatment can be reduced to RMB 200,000. Additionally, patients outside Hangzhou may qualify for partial reimbursement through assistance programs offered by the China Primary Health Care Foundation.

There are over 200 types of primary intracranial tumors, among which gliomas have one of the poorest cure rates. Data indicate that the incidence of gliomas is 5–8 per 100,000 people, accounting for approximately half of all intracranial tumors, with more than 45,000 new cases diagnosed annually in China. In 2018, Codon Publications released Glioma, noting that only a small proportion of glioma patients survive beyond 2.5 years, the five-year survival rate is less than 5%, and nearly all patients experience tumor recurrence. Over the past three decades, despite continuous advancements in neurosurgical techniques for glioma resection, the five-year survival rate for glioma patients has not improved significantly.

According to data from the U.S. Centers for Disease Control and Prevention (CDC), brain tumors have surpassed hematologic malignancies (leukemia) to become the leading cause of cancer-related deaths in children since 2014. The blood-brain barrier, the brain’s natural protective shield, is a major reason why conventional chemotherapy, targeted therapies, and even immunotherapies struggle to completely eradicate cancer cells within the brain.

Tumor Treating Fields (TTFields) is a cancer therapy that utilizes specific electric field frequencies to interfere with cell division, inhibit tumor growth, and induce death in affected cancer cells. These fields do not stimulate human tissues or cause tissue heating; instead, they specifically target dividing cancer cells of a particular size, causing minimal harm to healthy cells. The most common adverse reaction is mild to moderate skin irritation.

In reality, the human body is an irregular conductor, and various neural and muscular activities within it are mediated by electricity. Various electricity-based physical therapies are widely used in multiple medical fields, such as defibrillators for cardioversion, transcutaneous electrical nerve stimulation (TENS) for pain management, deep brain stimulation (DBS) for treating Parkinson’s disease, transcranial magnetic stimulation (TMS) for treating psychiatric disorders, and radiofrequency ablation (RFA) for treating cardiac diseases.

During the use of Optune, four electrode transducer arrays are placed on four specific locations on the patient’s scalp, generating low-intensity, intermediate-frequency alternating electric fields that kill cancer cells in the patient’s brain.

In 2004, a team led by Israeli scientist Yoram Palt published a paper in *Cancer Research*, concluding that low-intensity (<2 V/cm) intermediate-frequency electric fields (100–300 kHz) significantly inhibited the growth of various cancer cell lines. Electric fields at these frequencies can interfere with protein movement within cancer cells, preventing them from dividing into two cells or resulting in abnormal daughter cells, ultimately leading to apoptosis.

Another significant finding of this study is that medium-frequency electric fields induce apoptosis with virtually no typical side effects or damage. According to a paper published in The Journal of the American Medical Association (JAMA) in December 2015, combining tumor treating fields with temozolomide chemotherapy extended the progression-free survival of patients with glioblastoma from 4 months to 7.1 months and increased overall survival from 15.6 months to 20.5 months. A subsequent study published in JAMA in December 2017 demonstrated that the 5-year survival rate for glioblastoma patients receiving temozolomide combined with tumor treating fields also rose from 5% to 13%.

To date, tumor treating fields (TTFields) have been approved in certain countries and regions for the treatment of adult patients with glioblastoma and mesothelioma, and have been used to treat more than 15,000 patients with glioblastoma worldwide. In 2013, TTFields were included in the National Comprehensive Cancer Network (NCCN) Guidelines in the United States. In December 2018, the “Specifications for Diagnosis and Treatment of Gliomas (2018 Edition)” issued by the National Health Commission of China also specifically recommended TTFields for newly diagnosed glioblastoma (Level 1 evidence) and recurrent high-grade gliomas (Level 2 evidence).

In addition, multiple global Phase III pivotal clinical trials evaluating the efficacy of tumor treating fields for brain metastases, non-small cell lung cancer, pancreatic cancer, and ovarian cancer, as well as Phase II clinical trials targeting liver cancer and gastric cancer, are currently underway.

As the world’s first and only tumor treating fields product approved by the U.S. FDA, Optune was approved in 2011 and 2015 for the treatment of adult patients with recurrent and newly diagnosed glioblastoma, respectively.

In September 2018, Zai Lab obtained an exclusive license from Novocure to develop and commercialize Tumor Treating Fields technology in the Greater China region. Meanwhile, Zai Lab will collaborate with Novocure on the development of additional indications globally. Novocure was founded by Israeli scientist Yoram Palt, who discovered that intermediate-frequency electric fields inhibit the growth of cancer cell lines.

In December of that year, a glioblastoma patient in Hong Kong was the first to undergo tumor treating fields therapy. In March of the following year, Optune received approval for market launch in Hong Kong, achieving sales revenue of $6.4 million within the same year.

In May 2020, the National Medical Products Administration (NMPA) approved the marketing application for Optune, to be used in combination with temozolomide for the treatment of patients with newly diagnosed glioblastoma, and as a monotherapy for patients with recurrent glioblastoma. This marked the first innovative therapy for glioblastoma approved in mainland China in 15 years. It is reported that in January 2020, Zai Lab initiated an exploratory Phase III clinical study to evaluate the safety and efficacy of Optune combined with chemotherapy as first-line treatment for patients with gastric adenocarcinoma, enrolling the first patient, and prepared to submit a marketing application for Optune for the treatment of malignant pleural mesothelioma.

Meanwhile, to enhance the accessibility of Optune, Zai Lab partnered with Ping An Health Insurance and MedxHealth immediately upon its market launch to include it in the Hangzhou Citizen’s Supplementary Medical Insurance.

“In the future, we will continue to develop an innovative, people-centric model that integrates healthcare with insurance, safeguarding users’ life and health,” stated Liang Yi, Chief Commercial Officer and President of Greater China at Zai Lab, in a media interview following the commercial channel launch event for Optune® in China. Zhang Xiaodong, CEO of Medbanks Health, also pointed out, “The launch of Optune® marks our first breakthrough and integration in combining financial services with innovative medical devices. We hope that through further exploration of innovative services, we can truly and effectively help patients alleviate their financial burden and improve access to treatment.”

To date, Zai Lab’s oncology drug “Zejula” and tumor treating fields therapy “Optune” have been successfully launched in Hong Kong, China, and mainland China. Notably, Zejula has ranked among the top five oncology drugs by sales revenue during its first full year post-launch in Hong Kong.

As the commercialization of its products accelerated, Zai Lab experienced rapid revenue growth over the past two years. Annual report data show that Zai Lab’s revenue reached US$12.985 million in 2019, representing a nearly 100-fold increase from US$129,500 in 2018. Meanwhile, as a biotechnology company, Zai Lab has never spared investment in research and development (R&D). According to the annual report, the company’s R&D expenses amounted to US$142 million in 2019, a year-on-year increase of 18.2%.

Currently, in addition to the two products already on the market, Zai Lab has one product under marketing application review, while eight other products are in various stages of clinical trials. Furthermore, after years of learning and development focused on cutting-edge global therapies, Zai Lab’s independent R&D capabilities have made significant strides. The company is allocating part of its resources to early-stage drug discovery to address existing gaps, with a plan to submit one to two Investigational New Drug (IND) applications globally each year in the future. Liang Yi also stated that Zai Lab will continue to drive R&D innovation. While accelerating the market launch of innovative therapies, the company aims to collaborate with partners to build a sustainable, patient-centric new ecosystem for the commercialization of innovative treatments, thereby enabling these therapies to benefit more patients more rapidly.