Can Mylotarg, the world's first antibody coupled drug, be reborn in Nirvana seven years after its withdrawal from the market?

Source: medicine magic cube July 11, 2017-06-28, the antibody coupling drug Mylotarg (gemtuzumab ozogamicin) of Pfizer will be reviewed and evaluated by the FDA expert advisory committee again, at this time, it has been seven years since its withdrawal from the US in June 2010 If the results are optimistic, FDA will make a decision to approve the listing again in September Antibody coupled drugs (ADC) connect cytotoxic chemotherapy drugs with specific antibodies targeting tumor cell surface antigens through linkers, so that chemotherapy drugs can act on tumor cells more accurately and reduce the toxic and side effects on healthy tissues Currently, only three ADC drugs have been approved for marketing in the world, and Mylotarg is the first one Unfortunately, it was labeled as "withdrawal drug" At present, only Roche kadcyla has a good sales performance With a response rate of 26%, Mylotarg was approved by FDA on May 17, 2000 It is used to treat patients with first relapse, over 60 years old, CD33 +, and acute myeloid leukemia (AML) who are not suitable for cytotoxic chemotherapy In 2004, Wyeth launched a post marketing validation phase III study of Mylotarg, code named SWOG 106, to evaluate whether the combined use of Mylotarg on the basis of chemotherapy can prolong the life of patients However, in the early stage of SWOG 106 study, it was found that there was severe fatal liver injury in the treatment group of Mylotarg, and the mortality rate in the combination group was higher than that in the chemotherapy group alone (5.7% vs 1.4%), and there was no significant survival benefit Therefore, the study of SWOG 106 was terminated ahead of time Pfizer also announced the withdrawal of Mylotarg from the market in June 2010 After removing Mylotarg from the market, Pfizer joined hands with the French acute leukemia association Association, alfa) carried out a phase III, open label study, code named alfa-0701 278 newly diagnosed AML patients aged 50-70 were recruited They were given a combination treatment of chemotherapy drugs (daunorubicin + cytarabine) ± lower dose of Mylotarg (3mg / m2) It was expected that a larger cumulative dose could be achieved by increasing the frequency of Mylotarg administration while reducing toxicity The results showed that in the third year, the EFS of the combined drug group was significantly improved; in the second year, the EFS of the combined drug group was benefited, but in the third year, the EFS of the combined drug group was not significantly improved In terms of safety, the combination group did not cause a significant increase in mortality, although it would have refractory thrombocytopenia Detailed results were published at the ash2011 annual meeting The EFS Data of alfa-0701 study Pfizer resubmitted its application for the first-line treatment of AML with Mylotarg based on the results of alfa-0701 study and the meta-analysis of five phase III studies involving a total of 3000 patients Mylotarg was able to obtain accelerated approval in 2000, mainly due to the limited treatment options available to AML patients at that time Now, with the rise of a series of popular therapies and targets with significant therapeutic effects, such as tumor immunotherapy, Btk, Bcl-2, FDA may improve the listing standards of drugs Whether Mylotarg can be re launched remains to be seen.