Pfizer’s antibody-drug conjugate for leukaemia given breakthrough status

Pfizer’s candidate treatment for acute lymphoblastic leukaemia (ALL) inotuzumab ozogamicin has been given breakthrough status by the US FDA.

The designation comes on the back of the phase III INO-VATE ALL trial, which enrolled 326 patients with relapsed or refractory CD22-positive ALL and compared inotuzumab ozogamicin to standard of care chemotherapy.

Results from the study – presented at this year’s European Hematology Association (EHA) meeting – showed that the drug was able to achieve a complete response rate of more than 80 percent in patients with relapsed or refractory ALL, more than twice the response rate in the chemotherapy group.

The trial is continuing to evaluate overall survival, which is a separate primary end point, and that data will be submitted for presentation at upcoming medical meetings, according to the company.

ALL is typically a disease of childhood, with more than two-thirds of cases affecting children. Current treatments have led to a cure rate of approximately 80 percent for children with ALL.

However, the long-term prognosis for adult patients with this form of leukaemia remains poor with overall cure rates of only 30–40 percent, and five-year survival is very low in relapsed patients. Around 6,000 patients are diagnosed with ALL each year in the US.

Inotuzumab ozogamicin is an antibody-drug conjugate (ADC), which combines an antibody component targeting CD22 – a surface protein found on malignant cells – with a cancer-killing compound called calicheamicin.

The antibody is designed to target ALL cells and be absorbed into them, at which point it delivers the cell-killing payload. It is also in trials involving elderly patients with ALL and in patients with CD22-positive lymphoid malignancies.

Pfizer’s drug is one of a handful of new drugs emerging onto the market for ALL, with others including Talon Therapeutics’ already-approved liposomal formulation of vincristine Marqibo and Erytech Pharma’s Graspa, a red blood cell-encapsulated formulation of L-asparaginase that is in the registration phase in Europe.

“Advancing therapies for patients with adult acute lymphoblastic leukemia is crucial as only 10 percent of adults with ALL who relapse after first-line therapy survive five years or more with current treatment options,” said Pfizer’s chief medical officer Mace Rothenberg.

Inotuzumab ozogamicin has also been tested as a treatment for patients with relapsed or refractory aggressive non-Hodgkin lymphoma (NHL), but this was stopped earlier this year after it became apparent there was no additional benefit with the drug over standard therapy.

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