Pfizer's fast-tracked leukaemia candidate could rival CAR-Ts
Pfizer has filed its armed antibody, inotuzumab ozogamicin with the US regulator, for a difficult-to-treat type of acute lymphoblastic leukaemia (ALL).
The FDA has granted a faster six-month review for inotuzumab ozogamicin in adults with relapsed or refractory B-cell precursor acute lymphoblastic leukaemia.
For patients with relapsed or refractory adult ALL, the five-year overall survival rate is less than 10 percent, and numerous companies are looking at how to tackle the condition.
Pfizer's drug could go head-to-head with a wave of new CAR-T drugs set to reach the market over the next few years. This includes Novartis' CTL019, which the company plans to file in ALL, although it is targeting paediatric and young adults rather than the adult cohort selected by Pfizer.
Analysts predict that if approved, Pfizer's drug could generate peak sales exceeding $2 billion.
Originally developed by Pfizer and Celltech – now part of UCB –the drug is an antibody-drug conjugate combining a monoclonal antibody that binds to specific receptors on a cancer cell, then delivers a dose of a cytotoxin that kills the cell.
The filing represents a second attempt for the molecule, as it failed in phase 3 trials in non-Hodgkin's lymphoma four years ago.
But the phase 3 INO-VATE trial in 322 patients reported last June was a significant success. It saw remission rates and two-year survival rates more than double in patients taking the drug in comparison to standard of care chemotherapy.
Novartis' pivotal ELIAN trial for CTL019 was in a very similar set of patients, though its study was in a much smaller group of 50 patients. It also showed very promising results, with 82% of patients achieving complete remission or complete remission with incomplete blood count recovery at three months post-infusion.
Pfizer is determined to add to its portfolio of cancer drugs, as demonstrated when it outbid rivals including Sanofi for cancer drugs firm Medivation last summer, snapping up the California-based biotech for $14 billion.
It wants to build on the success of its recently launched Ibrance (palbociclib) breast cancer pill, which generated sales of more than $2 billion last year.
Inotuzumab ozogamicin already received Breakthrough Therapy designation from the FDA in October 2015 and the Priority Review status accelerates the FDA review time from 10 months to a goal of six from the day of filing.
The European Medicines Agency is also reviewing the drug, and both dossiers are based on results from the phase 3 INO-VATE 1022 trial, which enrolled 326 adults with relapsed or refractory B-cell ALL and compared inotuzumab ozogamicin to standard of care chemotherapy.
The INO-VATE 1022 study had two independent primary endpoints, complete response with or without hematologic remission (CR/CRi) and overall survival (OS).
The antibody-drug conjugate targets CD22, a cell surface antigen expressed on around 90% of B-cell malignancies, giving it scope for many more indications.
When inotuzumab ozogamicin binds to CD22, it is internalised where the cytotoxic agent calicheamicin is released to destroy the cell.
The most common adverse events were reduction in blood cell count, include febrile neutropenia. This side-effect profile might well compare favourably to Novartis' CTL019, which produced grade 3 or 4 cytokine release syndrome (CRS) in nearly half of study patients.
Pfizer's drug will also have the advantage of being far less complicated to manufacture than autologous CAR-T treatments, which require T-cells to be harvested from each patient and then engineered to target cancer cells.
The FDA is set to make a decision on Pfizer's drug in August, which means it should gain approval ahead of Novartis' treatment.
Pfizer also has a stake in CAR-T drugs itself, working with Servier on UCART19, also targeting ALL.
