Reshaping destiny: China's first adult thalassemia gene therapy patient heads to university

"I received my university admission letter!" Doudou (pseudonym), upon receiving the admission letter, immediately shared her joy with Reforgene.

Two and a half years ago, Doudou, like other patients with severe thalassemia, struggled with regular blood transfusions and iron chelation treatment under the meticulous care of her grandmother. In 2022, Doudou received treatment with RM001, a beta-thalassemia gene editing medicine developed by Reforgene. Half a month later, she completely escaped transfusion dependence, achieving "liberation from thalassemia" and becoming China's first successful case of curing adult severe beta-thalassemia. Doudou's cure was widely reported and greatly encouraged many thalassemia patients. Now, more than 30 months later, Doudou has long fully integrated into normal life and is about to enter university, opening a new chapter of her life.

A thalassemia girl with a troubled fate: her grandmother became the light of her life

The growth path of many thalassemia children is full of unimaginable hardship. Under heavy economic burden and mental pressure, some parents of affected children choose to divorce, and these disease-ravaged children can only be raised by single parents or grandparents, making life even harder. Doudou, who participated in Reforgene's clinical research, was fortunate: her grandmother cared for her with constant love. This resilient elderly woman tried her best to safeguard Doudou's growth.

The grandmother went everywhere to find treatment opportunities for Doudou, paying special attention to the blood transfusion issue. Even when her own health was frail, she insisted on taking Doudou back and forth between Wuming and Nanning for transfusion treatment. To prevent Doudou from being discriminated against because of her illness, the grandmother also went to the school to educate teachers and students about thalassemia. Her resilience and dedication were like a beam of light illuminating Doudou's life.

Under her grandmother's care, Doudou successfully passed the threshold of adulthood. For thalassemia patients, one option is to wait for a suitable HLA match for allogeneic hematopoietic stem cell transplantation (commonly known as bone marrow transplantation), but because matching opportunities are very rare and waiting times long, only a very few lucky patients can achieve it. On the other hand, Doudou had no siblings as matching donors, so she missed the best window for traditional transplantation. As she grew older, the symptoms of thalassemia gradually worsened her physical condition, and the hope of cure became increasingly remote. "If my grandmother passes away, I won't be able to live on either." This was Doudou's heartfelt voice and the heavy problem before her. On one side was her aging grandmother; on the other was endless transfusion treatment. How long could such a life last? Both Doudou and her grandmother knew the answer.

Fortunately, Doudou met Reforgene. The emergence of gene editing technology changed the fate of thalassemia patients.

Reforgene's RM001 rewrote Doudou's life

Professor Zhang Xinhua, an expert in the Department of Hematology at the 923rd Hospital of the PLA in Nanning, Guangxi, has rich clinical experience in thalassemia and has helped countless thalassemia patients over the years, earning the affection of these families. Zhang Xinhua knows the thalassemia children he has treated like the back of his hand, and Doudou is undoubtedly one of his most memorable patients.

By 2022, Professor Zhang Xinhua had accumulated preliminary clinical experience in gene editing treatment of severe thalassemia. After continuous communication with Reforgene's technical team, he showed great interest in RM001, the first novel-target gene editing medicine in China that activates the HBG gene. After a series of scientific and medical ethics approval procedures, Zhang Xinhua successfully cured two child patients, whose recovery speed was surprisingly fast, with data even superior to the clinical performance of similar drugs reported by American peers, laying a solid foundation for further clinical research in adult patients.

After in-depth communication with Reforgene's clinical team, the two sides decided to explore the field of gene editing treatment for adult patients. As is well known, traditional bone marrow transplantation has age limits. For patients like Doudou, considering clinical benefits and risks such as immune rejection, subsequent complications and transplantation success rate, bone marrow transplantation is usually not appropriate. Transplantation in older patients is the deep-water zone, or even a forbidden zone, of clinical practice. However, the large number of older patients still has strong treatment needs; the calls of patient families and the desire for survival know no age.

Against this background, Reforgene's attempt is of epoch-making significance for China's thalassemia clinical practice. If clinically successful, this will mark China's first cure of older patients with a gene medicine, providing adult patients with a safe and efficient curative treatment option, and will also demonstrate the leading position of Chinese medicine in the global thalassemia field.

After a systematic assessment of Doudou's medical history and current condition, combined with the preclinical research and clinical data of RM001, Zhang Xinhua's medical team was full of confidence in curing Doudou. With full informed consent, Doudou and her grandmother decided to participate in this gene editing medicine clinical research that could change their fate. In early February 2022, Doudou was admitted to hospital, received RM001 treatment on February 15, and escaped transfusion dependence about 20 days later, becoming China's first adult thalassemia patient cured through gene editing.

This pioneering clinical research opened a new path for the cure of older thalassemia patients. With the market launch of the medicine, the plight of this patient group in China is expected to be fundamentally improved in the near future. This is also the concrete practice of Reforgene's mission of providing curative medicines for patients.

Doudou's successful treatment verified for the first time that gene editing treatment has the same excellent curative effect in older patients as in children and adolescents. Compared with allogeneic hematopoietic stem cell transplantation, this innovative gene medicine places much lower requirements on the patient's physical condition. For adult patients with severe beta-thalassemia, we can confidently give the answer of cure. This is undoubtedly a ray of dawn for the entire group of patients with severe thalassemia. Doudou shared her experience at a thalassemia organization exchange meeting, igniting the spark of hope for more fellow patients.

Now, after a year of recovery, Doudou has entered a new stage of life: she took the college entrance examination and was successfully admitted to university. Unlike before, she will no longer bear the heavy burden of thalassemia. "Next it's my turn to take care of my grandmother." A beautiful life is opening its arms to her.

More "Doudous" cured by Reforgene's gene editing medicine

So far, not only Doudou, but also nearly twenty other patients treated with Reforgene's gene editing medicine RM001 have achieved success, continuously escaping transfusion dependence and returning to normal life.

Among these cured "Doudous", some share the joy of winning a folk "snatching the embroidered ball" competition, some send wonderful moments from a children's palace art competition, and some show their style in amateur combat sports. Among them, a 25-year-old adult patient has already started working and become a builder of society... Their fates have been changed, and they have begun brand-new lives.

Gene editing technology benefits humanity. Reforgene always upholds the purpose of innovation for life and is dedicated to the R&D of innovative gene editing medicines. In the thalassemia field, it is worth noting that Reforgene has not only developed curative innovative medicines for beta-thalassemia, but another innovative medicine for alpha-thalassemia also achieved a world-first breakthrough in April this year, becoming the world's first gene editing medicine for alpha-thalassemia and achieving the first successful cure of a patient.

The development of life sciences and genomic medicine is accelerating the birth of disruptive pharmaceutical products. Reforgene is a leading enterprise in the gene editing medicine direction among them. The breakthrough achievements of thalassemia medicines provide an inspiring example of the health application of China's innovative technological strength. With the advancement of pivotal clinical trials of this medicine, China's thalassemia patients are expected to usher in an era of cure in the near future. Safety, efficiency and cure will be the strongest answers to patients.

RM001

RM001 is a beta-thalassemia gene editing medicine independently developed by Reforgene. Through CRISPR gene editing technology, it modifies the patient's autologous hematopoietic stem cells, activating the body's natural fetal hemoglobin (HbF) synthesis, restoring normal physiological function of red blood cells and freeing patients from blood transfusion, achieving the goal of a one-time administration to cure beta-thalassemia. RM001 adopts an editing strategy that directly targets the promoter of the gamma-globin genes (HBG1/2), which does not affect the expression of other functional genes of hematopoietic stem cells and their differentiated functional cells, and is safer.