After 7 years of withdrawal, can the world's first antibody-conjugated drug Mylotarg be reborn?

- Jul 17, 2018-

On July 11, Pfizer's antibody-conjugated drug Mylotarg (gemtuzumab ozogamicin) will be reviewed again by the FDA's Expert Advisory Committee, which has been a full seven years since its withdrawal from the US in June 2010. If the results are optimistic, the FDA will make a decision to approve the listing again in September.



  Antibody-conjugated drugs (ADCs) link cytotoxic chemotherapeutic drugs to specific antibodies that target tumor cell surface antigens via linkers, allowing chemotherapeutic drugs to act more precisely on tumor cells and reduce toxicity to healthy tissues. Side effects (see: Magic bullets fly up - talk about antibody-conjugated drugs). At present, only three ADC drugs are approved for marketing in the world. Mylotarg is the first one, but it was unfortunately labeled as “withdrawal drugs”. At present, only Roche Kadcyla's sales are not bad.



Mylotarg was approved by the FDA on May 17, 2000 with a 26% response rate for the treatment of patients with acute myeloid leukemia (AML) who were relapsed for the first time, over 60 years of age, CD33+, and were not eligible for cytotoxic chemotherapy. In 2004, Wyeth launched a confirmatory Phase III study of Mylotarg, codenamed SWOG 106, to assess whether the combination of Mylotarg based on chemotherapy can prolong patient life.



However, in the early stage of the SWOG 106 study, it was found that the Mylotarg treatment group had severe fatal liver injury. The mortality rate of the combination group was higher than that of the chemotherapy group alone (5.7% vs 1.4%), and did not show significant survival benefit. The SWOG 106 study was terminated early, and Pfizer also announced the withdrawal of Mylotarg from its market in June 2010.



After the withdrawal of Mylotarg, Pfizer and the Acute Leukemia French Association (ALFA) conducted a Phase III, open-label study, codenamed ALFA-0701, and recruited 278 patients with newly diagnosed AML from 50 to 70 years of age. A combination of chemotherapy drugs (daunorubicin + cytarabine) ± lower dose Mylotarg (3 mg/m2) is expected to achieve a larger cumulative dose by increasing the frequency of Mylotarg administration while reducing toxicity.


The results showed that in the third year, the event-free survival (EFS) of the combination group was significantly improved; the combination group had a benefit to the overall survival at the second year, but the overall survival at the third year was improved. Not obvious. In terms of safety, although the combination group developed refractory thrombocytopenia, it did not cause a significant increase in mortality. Detailed results were published at the ASH2011 conference.

ALFA-0701 research EFS data


Pfizer's resubmission of Mylotarg's first-line treatment for AML is based on the ALFA-0701 study and a meta-analysis of five Phase III studies involving a total of 3,000 patients.


Mylotarg was able to get accelerated approval in 2000, mainly because AML patients had very limited treatment options at the time. Now with the rise of a series of popular therapeutics and targets with tumor immunotherapy, BTK, BCL-2, etc., the FDA may raise the market for drugs. Whether Mylotarg can be re-listed, we will wait and see.

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