Takeda's Innovative Drug Teduglutide Approved in China, Transforming the Lives of 'Short Bowel Syndrome' Patients

ShanghaiFebruary 23, 2024/PR Newswire/ -- Takeda China announced today that its gastrointestinal product, Rewixu^®(Generic name: Teduglutide for injection) has officially been approved by the National Medical Products Administration (NMPA) of China for the treatment of short bowel syndrome (Short Bowel Syndrome, abbreviated as SBS) in adult patients and pediatric patients aged 1 year and above. The drug should only be used after a period of intestinal adaptation, when the patient's condition is stable and dependent on parenteral nutrition support. Teduglutide is the first of its kind in China.^[1]A glucagon-like peptide-2 (GLP-2) analog for the treatment of short bowel syndrome fills the gap in the field of long-term intestinal rehabilitation therapy, providing Chinese patients with a new treatment option and helping the "short bowel population" regain a new lease on life.

Mr. Guohong Shan, Global Senior Vice President of Takeda Pharmaceutical Company Limited and President of Takeda ChinaExpressed: "We are very grateful for a series of measures and policies encouraging innovative drugs by relevant government departments in recent years, which enabled the rapid approval of Teduglutide to benefit patients with short bowel syndrome. This drug once utilized the spillover effect of the CIIE (China International Import Expo), achieving the transformation from 'exhibit to product' in just six months, allowing patients in Boao to use the drug on a trial basis. Today, only nine months later, it has welcomed its official approval. This acceleration highlights the relentless efforts and work done by the government and relevant departments in persistently encouraging innovation and benefiting patients. Adhering to the concept of 'patients first,' in the future, Takeda will continue to accelerate the introduction of more globally innovative products to meet the unmet clinical needs of Chinese patients, enabling them to benefit from highly innovative drugs and transformative therapies."

Short Bowel Syndrome refers to a condition where extensive small bowel resection or bypass due to various causes significantly reduces the effective absorptive area of the intestine, and the remaining functional bowel cannot meet the nutritional needs of the patient or support growth in children. This leads to a syndrome primarily characterized by diarrhea, acid-base/water/electrolyte imbalance, and malabsorption and metabolic dysfunction. The normal adult small intestine measures about 3-8.5 meters, whereas in patients with short bowel syndrome, the small intestine is often less than 2 meters, and may even be less than 1 meter.^[2],[3].After intestinal surgery, almost all patients with short bowel syndrome require parenteral nutrition (PN) support to maintain and improve nutritional needs, especially for patients with incomplete intestinal adaptation, who may need to rely on PN for life. "Short bowel people" are an ultra-rare group, with an estimated prevalence of about 0.73/1,000,000 in China.^[4], and there is an increasing trend in the incidence year by year.^[5]。

Previously, patients with short bowel syndrome in China were in a treatment dilemma of "lacking effective drugs," and thus often had to rely on PN and intravenous infusion support for a long time.^[6]The 2023 Survey Report on the Diagnosis, Treatment, and Disease Burden of Chinese Patients with Short Bowel Syndrome shows that patients receiving PN treatment have an average annual infusion of 191 days, while underage patients have an average annual infusion of 257 days. Long-term PN support therapy can lead to severe, potentially life-threatening complications and impact quality of life in multiple ways.^[7]In addition, the clinical management of short bowel syndrome involves substantial direct and indirect economic costs.^[8], patients face a significant economic burden.

Intestinal rehabilitation therapy can enhance the absorption function of the remaining intestinal tract, helping to reduce the dosage of PN or even eliminate the dependence on PN. Teduglutide, an innovative drug for intestinal rehabilitation, is currently the only one of its kind globally.^[9]Approved human glucagon-like peptide 2 (GLP-2) analog, studies have confirmed^[5]Teduglutide can increase villus height and crypt depth, strengthen the intestinal epithelial barrier, thereby reducing local inflammation and improving intestinal permeability, and promoting intestinal adaptation.

This approval is based on the results of global and Japanese Phase III clinical trials for adult and pediatric patients with short bowel syndrome. The pivotal Phase III study for adult patients with short bowel syndrome is the STEPS study (CL0600-020).^[10]A 24-week study enrolled 86 patients dependent on PN. The primary endpoint analysis showed that after 24 weeks of treatment with teduglutide, 63% of patients had a ≥20% reduction in PN requirements, with a significantly higher response rate compared to the placebo group (30% of patients). The most common adverse reactions were abdominal pain and bloating, respiratory tract infections, nausea, etc., most of which were mild or moderate. A long-term open-label extension study, STEPS-2 (CL0600-021), enrolled 88 patients with short bowel syndrome and intestinal failure (SBS-IF). The primary endpoint analysis showed that after 30 months of teduglutide treatment, 93% of patients had a ≥20% reduction in PN requirements, and 33% of patients completely discontinued PN.^[11], no new safety signals were detected.^[10]In a pivotal Phase III study (TED-C14-006) involving 59 pediatric patients aged 1 to 17 with short bowel syndrome who were dependent on PN, the primary endpoint analysis after 24 weeks of treatment with teduglutide showed that 69% of pediatric patients had a ≥20% reduction in PN requirements, and 12% of pediatric patients completely discontinued PN.^[12]The safety profile of Teduglutide in pediatric patients is similar to that in adults, with no new safety signals identified in the long-term extension study with up to 69 weeks of exposure.^[13]. In addition, other studies (Phase III CL0600-004^[14], Phase III CL0600-005^[11], Phase III STEPS-3 TED-C11-001^[15], Phase III TED13-003^[16], Phase III SHP633-304^[17], Phase III Retrospective and Prospective Study SHP633-303^[18]) also demonstrated the good efficacy and safety of teduglutide.

Professor Cai Wei, Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine"It is very encouraging to see the approval of teduglutide, which provides us doctors and patients with a new 'therapeutic weapon,' and will also redefine intestinal rehabilitation treatment, opening a new chapter in the treatment of short bowel syndrome. Thanks to the 'Pilot First' policy in Boao Lecheng, Hainan, five pediatric patients have already been treated with teduglutide, and the overall clinical feedback has been positive. This not only demonstrates the vivid benefits of national policy advantages for patients but also reflects how innovative therapies bring new hope and health benefits to patients and their families. As doctors, we look forward to seeing more patients reduce or even eliminate their dependence on parenteral nutrition in the future, improve their quality of life, rewrite the fate of being 'tied to an IV bag,' and enjoy a high-quality, healthy life with freedom."

Dr. Wang Lin, Global Vice President of R&D at Takeda and Head of the Asia-Pacific R&D Center"We are delighted to see the rapid and successful approval of Teduglutide for Injection, which will provide a new treatment option for adult and pediatric patients over one year old with Short Bowel Syndrome (SBS), a rare disease in China, significantly improving patients' quality of life. Currently, the prevalence of SBS is extremely low, but the incidence trend is increasing year by year. Teduglutide for Injection is an accelerated development by Takeda based on the actual needs of Chinese patients, aiming to fill the long-standing gap in available treatments for this condition in China. In the future, Takeda will continue to combine global leading technologies with insights and experience in Asia, further accelerating the R&D and approval of innovative global drugs in China to benefit more Chinese patients as soon as possible."

Currently, Teduglutide has been included in the overseas special drug lists of five provincial or municipal惠民保 (mutual aid insurance) programs in Shanxi Province, Suzhou and Wuxi cities in Jiangsu Province, Lanzhou city in Gansu Province, and Hebei Province. Insured patients receiving treatment at designated medical institutions in Boao Lecheng, Hainan, can apply for claims, which will also reduce the financial burden on patients using the drug. With the approval of Teduglutide, Takeda Pharmaceutical Company Limited will further expand the depth and breadth of its patient services in the future. Collaborating with patient organizations, public welfare organizations, corporate partners, and other parties, Takeda aims to build a diversified, multi-dimensional support system for patients, encompassing diagnosis and treatment, multi-level protection, and long-term care including physical and mental rehabilitation.

[1] As of February 2024

[2] Li Yousheng, Cai Wei, Li Jieshou, et al. Chinese Consensus on Diagnosis and Treatment of Short Bowel Syndrome (2016 Edition) [J]. Chinese Medical Journal, 2017, 97(8): 569-576.

[3] Clinical Gastroenterology and Hepatology.2006;4:6–10

[4] Prevalence Estimation Of Short Bowel Syndrome In Chinese Adult Population: A Systematic Review And Meta-analysis

[5] Kounatidis D, et al. Curr Nutr Rep. 2022 Aug 6.

[6] "Survey Report on the Diagnosis, Treatment Status, and Disease Burden of Short Bowel Syndrome Patients in China 2023"

[7] Jeppesen PB. J Parenter Enteral Nutr. 2014, 38(1): 8S-13S

[8] J Schalamon, et al. Best Pract Res Clin Gastroenterol. 2003. 17(6): 931-942.

[9] As of February 2024

[10] Jeppesen PB et al. Gastroenterology. 2012;143:1473–81.

[11] Schwartz LK et al. Clin Transl Gastroenterol. 2016;7:e142.

[12] Kocoshis SA, et al. J Parenter Enteral Nutr. 2020;44:621-31.

[13] Instructions for Use of Teduglutide for Injection

[14] Jeppesen PB et al. Gut. 2011;60:902–14

[15] Seidner DL et al. Nutr Clin Pract. 2018;33:520–7.

[16] Carter BA, et al. J Pediatr. 2017;181:102-11.e5.

[17] Mercer D, et al. J Pediatr Gastroenterol Nutr. 2019;69(suppl.2):S289-90.

[18] Carter BA, et al. J Pediatr Gastroenterol Nutr. 2019;69(suppl.2):S275.