Car-t cell therapy killer! Tafasitamab, a new type of immunoenhancement monoclonal antibody targeting at CD19, has been applied for marketing in the United States to treat B-cell tumors!

December 31, 2019 / BIOON / -- morphasys is a clinical stage German biopharmaceutical company dedicated to developing innovative and differentiated therapies for critical patients It is worth mentioning that recently, tremfya (Chinese trade name: tenoya, general name: guselkumab, gussechiumab), a proprietary antibody technology product of morphasys, was approved by China Drug Administration (nmpa) to be marketed in the mainland This drug is a product of Johnson & Johnson for adults with moderate and severe plaque psoriasis suitable for systematic treatment Recently, morphasys company announced that it has submitted the biological product license application (BLA) of tafasitamab (mor208) to the U.S Food and Drug Administration (FDA), and combined with lenalidomide to treat patients with relapsed or refractory diffuse large B-cell lymphoma (R / R DLBCL) Tafasitamab is a new humanized monoclonal antibody targeting at CD19, which is a clear biomarker of B cell malignancies The FDA has a 60 day filing review period to determine if the BLA is complete and accepted Dr Malte Peters, chief development officer of morphasys, said: "this BLA submission marks an important milestone in the history of morphasys and shows our commitment to addressing the high medical needs in recurrent or refractory dlbcls If approved, the tafasitamab + lenalidomide regimen will be an alternative treatment option for patients with this serious disease " The expression of CD19 and the mechanism of tafasitamab in different stages of B cell development Tafasitamab is a humanized FC enhanced monoclonal antibody targeting CD19 The Fc domain of tafasitamab is modified (containing two amino acids instead of s239d and i332e) By increasing the affinity for the activated FC γ riiia on the effector cells, it can significantly enhance the antibody dependent cell-mediated cytotoxicity (ADCC) and antibody dependent cell phagocytosis (ADCP), so as to improve the tumor The key mechanism of cell killing In preclinical model studies, tafasitamab has been shown to induce direct apoptosis of cancer cells by binding to CD19 At present, tafasitamab is being developed for two kinds of B-cell malignant tumors, including DLBCL and CLL Globally, DLBCL is the most common type of non Hodgkin's lymphoma (NHL) in adults, accounting for 40% of all cases; CLL is the most common type of leukemia in adults In terms of regulation, the FDA granted tafasitama breakthrough drug qualification (BTD) in October 2017, and lenalidomide was used to treat R / R DLBCL patients who were not suitable for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) In 2014, FDA granted tafasitamab the fast track qualification (FTD) for R / R DLBCL treatment Also in 2014, FDA and EMA awarded tafasitamab the orphan drug qualification to treat DLBCL and CLL / SLL (small cell lymphoma) This BLA submission is based on the main analysis results of the l-min study from tafasitamab combined with lenalidomide in R / R DLBCL patients and the results of a retrospective observational study Re-Min matching the control cohort to evaluate the efficacy of lenalidomide in R / R DLBCL patients ——L-mind: a single arm, open label phase II study is evaluating R / R DLBCL patients who have previously received at least one but no more than three therapies (including an anti-CD20 targeted therapy such as rituximab), who are not eligible for high-dose chemotherapy (HDC), and subsequent autologous stem cell transplantation (ASCT) In May this year, the l-mind study reached the main end point: the overall response rate (ORR) of tafasitamab + lenalidomide was 60%, and the complete response rate (CR) was 43%; the median progression free survival period (PFS) was 12.1 months when the median follow-up was 17.3 months; the remission was persistent, and the median duration of remission (DOR) was 21.7 months At a median follow-up of 19.6 months, the median overall survival (OS) was not reached (95% CI: 18.3 months NR), and the 12-month survival rate was 73.3% ——Re Min: it is an observational and retrospective study aiming at real world data, aiming to separate the contribution of tafasitamab in the scheme of combined medication with lenalidomide and prove the effect of combined therapy This study compared the real world response data of R / R DLBCL patients treated with lenalidomide and the efficacy of tafasitamab combined with lenalidomide in the l-min study The study collected data of 490 patients with R / R DLBCL who were not eligible for transplantation in the United States and Europe 76 of them matched with 76 patients in the l-mind study in terms of important baseline characteristics The analysis shows that the study has reached the main end point: the combination therapy of tafasitamab and lenalidomide has clinical advantages compared with the single drug therapy of lenalidomide The specific data are as follows: compared with lenalidomide, tafasitamab + lenalidomide combination therapy has statistically significant advantages in the primary end point orr (ORR: 67.1% vs 34.2%, P < 0.0001), and also has the same advantages in all secondary end points, including complete remission rate (Cr: 39.5% vs 11.8%, P < 0.0001), total survival time (median OS: less than 9.3 months, P < 0.0008) Some analysts pointed out that tafasitamab will directly challenge two anti-CD19 car-t therapies on the market for R / R DLBCL, namely, Novartis kymriah and Geely's yescarta Car-t therapy is different from conventional small molecule or biological therapy It is a living T cell therapy product Both kymriah and yescarta treatment processes need to separate patients' T cells, and carry out gene modification in vitro to make T cells express a chimeric antigen receptor (car) aimed at CD19 After that, the modified T cells will be sent back to patients to find the cancer cells expressing CD19, so as to play a therapeutic role In terms of efficacy, tafasitamab was comparable with kymriah and yescarta In terms of medication, kymriah and yescarta need to be prepared separately for each patient, which takes a certain time Tafasitamab is an industrial ready to use monoclonal antibody, which can be used at any time In terms of treatment cost, kymriah and yescarta both price hundreds of thousands of dollars, while tafasitamab can control very low Some analysts compare tafasitamab to "car-t cell therapy killer" If the drug is successfully launched, it will have a huge impact on kymriah and yescarta Source: morphasys announcements submission of biology license application for tafasitamab in R / R DLBCL to the FDA