Reforgene reports Phase I progress for its thalassemia gene editing drug RM001

With the rapid development of gene editing technology, Guangzhou Reforgene Medicine Co., Ltd. recently reported that its independently developed transfusion-dependent beta-thalassemia gene editing medicine RM001 has achieved leading excellent efficacy, with Phase I clinical trials nearing completion and some clinical data about to be announced at the 2023 American Society of Hematology Annual Meeting (ASH2023), expected to provide a brand-new treatment option for the cure of thalassemia patients worldwide.

The complete cure of thalassemia remains a major global medical challenge; it is the most common monogenic genetic disease with the largest affected population worldwide. The UK Medicines and Healthcare products Regulatory Agency (MHRA) recently approved Casgevy, jointly developed by CRISPR Therapeutics and Vertex Pharmaceuticals. This is the world's first approved gene editing therapy, proving the safety and efficacy of gene editing medicines in clinical treatment and opening the gene editing era of biomedicine.

Unlike Casgevy's strategy of indirectly increasing gamma-globin by targeting and reducing BCL11A expression, Reforgene's RM001 adopts a novel target, directly targeting the HBG promoter region. This is a modification strategy based on beneficial gene sequence variants naturally present in the population, with safety proven at the genetic level, avoiding differentiation and proliferation shifts of hematopoietic stem cells, thereby achieving safe cure for patients with severe beta-thalassemia.

So far, Reforgene's clinical trials have treated 16 patients with RM001 (68% with the severe β0/β0 genotype, compared with only 33.3% of β0/β0 in Casgevy's Phase I/II/III clinical trials). This makes it the gene medicine that has conducted clinical trials the earliest for this treatment strategy globally, cured the highest proportion of severe β0/β0 patients, and cured the most patients, as well as the gene editing medicine with the largest number of cured patients in clinical trials among domestic beta-thalassemia gene therapies. In addition to the high proportion of β0/β0 among treated patients, 75% (12/16) of the subjects treated with RM001 were over 12 years old (the older the thalassemia patient, the higher the risk and the more difficult the transplantation). It is also worth noting that the patients in its IIT clinical research include China's first adult beta-thalassemia patient and the first patient who had undergone splenectomy. These two subjects also carried alpha-thalassemia mutations, making this the first reported cure worldwide of patients with combined beta- and alpha-thalassemia.

In the clinical data of RM001, 7 IIT patients and 9 patients enrolled in the Phase I clinical trial (IND) all successfully escaped transfusion dependence after treatment. The longest follow-up time for patients is close to 2 years, with no product-related adverse events found. Among IIT patients, the median time to platelet engraftment was 16 days, the median time to neutrophil engraftment was 15 days, and the median time to stopping transfusion was 13 days. The data of patients enrolled in the Phase I IND trial also showed consistent significant effects, with a median platelet engraftment time of 25 days, a median neutrophil engraftment time of 15 days, and a median time to stopping transfusion of 24 days. In contrast, for the 48 subjects in the clinical trial of the just-approved Casgevy, the average platelet engraftment time was 44 days, the neutrophil engraftment time was 29 days, and the time to stopping transfusion was about 30 days. These comparative data not only prove the safety and efficacy of Reforgene's RM001, but also show that its treatment effect is superior to the UK's newly launched Casgevy (exa-cel) drug.

Overall, compared with the similar Casgevy (exa-cel) product, patients treated with RM001 achieve faster hematopoietic reconstruction, especially very rapid platelet recovery, shorter hospital stays, and lower risk of bleeding and severe infection. Even patients with the most severe genotype (β0/β0), those with combined alpha-thalassemia defects, and splenectomized patients can all achieve good treatment results and long-term freedom from transfusion.

Reforgene is a representative enterprise in China's gene editing drug innovation field, having achieved notable results in drug R&D for indications in hematology, ophthalmology, liver and central nervous system. Against the backdrop of increasingly globalized competition in biomedicine, the company is not only committed to providing curative medicines for patients with serious diseases including genetic diseases and high-incidence complex diseases, but has also accumulated original intellectual property in underlying editing technology tools, including a series of CRISPR/Cas and base editors at the DNA and RNA levels.

With the continued progress and success of RM001 clinical trials, Reforgene plans to conduct Phase II clinical trials in 2024. The successful application of this therapy provides a new treatment option for beta-thalassemia patients. This achievement of Reforgene demonstrates its unique competitiveness in the gene editing field and brings new hope and possibilities to the medical community. With technological progress and expanded application, Reforgene is expected to continue leading innovation in more major disease fields beyond beta-thalassemia, allowing more curative medicines to benefit patients worldwide.

Some clinical data of Reforgene's RM001 product have been published at the 2023 American Society of Hematology Annual Meeting (ASH2023); the ASH official website can be visited for details or to consult Reforgene.