Pfizer is to voluntarily withdraw its acute myeloid leukaemia treatment Mylotarg in the USA after a post-approval study raised concerns about the drug’s safety and clinical benefits.

Mylotarg (gemtuzumab ozogamicin) was given the green light in May 2000 under the US Food and Drug Administration’s accelerated approval programme for the treatment of relapsed AML based on overall response rate in three non-comparative studies. However the agency required a post-approval study to see whether adding Mylotarg to standard chemotherapy demonstrated an improvement in survival time to AML patients.

The 627 patient-trial, called SWOG S0106, began in 2004 but was stopped early after an interim analysis revealed that Mylotarg in combination with standard chemotherapy (daunorubicin and cytosine arabinoside) did not demonstrate improved survival compared with chemotherapy alone in patients with previously-untreated AML. Furthermore, 5.7% of patients in the Mylotarg plus chemotherapy arm died during treatment, compared to 1.4% on chemotherapy alone, and the FDA noted that at initial approval, Mylotarg was associated with a serious liver condition called veno-occlusive disease, which can be fatal; “this rate has increased in the postmarket setting,” the agency added.

Now, after “extensive discussions with the FDA”, the New York-headquartered giant has decided to withdraw its New Drug Application for Mylotarg, effective October 15. Mace Rothenberg, head of clinical development and medical affairs for Pfizer’s Oncology Business Unit, said “we are disappointed that the study did not confirm the clinical benefit” of the drug, adding that “our primary concern is for patients who
suffer from AML, which remains a very serious and difficult-to-treat disease with limited treatment options”. Patients who are currently taking Mylotarg may continue their course of therapy, in consultation with their doctors.

The financial impact is unlikely to be a problem, seeing as how less than 2,500 patients receive Mylotarg annually in the USA. It is the first drug approved under the accelerated review programme to be withdrawn from the market, but Robert Kane, acting deputy director for safety in the FDA’s Division of Haematology Products, was quoted as saying that the scheme “still has a place in the approval process but it’s also more important that we learn over the years that the whole development plan be set up well in advance”.

The four-year delay in starting SWOG S0106 after Mylotarg trial had been approved has raised eyebrows, but Dr Kane stated that this “highlights the need for greater oversight of follow-up studies” which, if possible, should be underway when a drugmaker submits an application for accelerated approval.