Amgen Drives Into Immunotherapy With Early Blinatumomab BLA
This article was originally published in The Pink Sheet Daily
Executive Summary
Bispecific leukemia drug goes to FDA ahead of Phase III data in what could be a signature moment for the agency’s breakthrough designation program – and the company’s cancer deal-making.
In an effort to prove its R&D engine hasn’t stalled and that moves into the hard-to-treat cancer space are paying off, Amgen Inc. opted for an early filing of its bispecific T-cell engager (BiTE) antibody blinatumomab, despite not having Phase III data in hand.
The big biotech announced Sept. 22 that it has filed a BLA for the mid-stage BiTE asset that it acquired in its January 2012 acquisition of Micromet Inc. for $1.16 billion (Also see "Amgen Gobbles Up Micromet In $1.16 Billion BiTE" - Pink Sheet, 26 Jan, 2012.).
Blinatumomab, which targets the CD19 and CD3 proteins, is being evaluated for the treatment of adults with Philadelphia negative (Ph-) relapsed/refractory B-cell precursor acute lymphoblastic leukemia (ALL).
BioMedTracker estimates the drug has an 89% chance of the regulatory agency approving it in ALL; the estimate is about 7% greater than average due to strong clinical trial results. BioMedTracker estimates a user fee date of May 22, 2015. Approval is not a sure thing, however; the antibody also has been associated with central nervous system adverse events.
The cancer drug earned an orphan designation for the indication since there are less than 6,000 patients diagnosed with ALL in the U.S. annually. It also garnered FDA’s breakthrough designation for the strong results it exhibited in Phase II testing. The submission was based on the Phase II results.
The open-label, single-arm, multicenter study tested blinatumomab (AMG 103) in 1,890 adults with relapsed/refractory ALL; results of the trial were first released at the American Society of Clinical Oncology meeting in June. About 43% (82 patients) of study participants had a complete response or complete response with partial blood count recovery (CR/CRh), the primary endpoint of the study.
CR/CRh rates of at least 30% were observed in all groups when patients were analyzed by number of prior salvage regimens, including the difficult subgroup of patients who had two or more prior salvage therapies or were primary refractory. This response rate compares favorably to late-line cytotoxic agents available for ALL (Also see "ASCO Immunotherapy Alert: BioMedTracker’s Top Abstract Picks" - Pink Sheet, 19 May, 2014.).
Amgen began Phase III testing of the drug in December. The Phase III TOWER study, which tests blinatumomab against the chemotherapy of choice in 400 adults with relapsed/refractory ALL, is ongoing. The National Cancer Institute recently launched two Phase III studies of blinatumomab in ALL. Amgen is also recruiting patients in a Phase II study of the drug in patients with Philadelphia positive (Ph+) relapsed/refractory B-cell precursor ALL (Also see "Amgen’s Bispecific Blinatumomab May Be Ready For Leukemia Filing" - Pink Sheet, 22 May, 2014.).
Proof Is In The Submission
“The filing for blinatumomab brings us a step closer to first realizing the potential of BiTE technology and represents our commitment to evaluating this novel approach in a broad range of difficult-to-treat cancers,” said Sean Harper, EVP of R&D at Amgen.
For Amgen, this is more than just the moving forward of its late-stage pipeline, but a demonstration that it is still able to deliver on its R&D engine, as well as a show that it can be a force in immunotherapy. The large biotech has faced criticism from the Street for the swath of aging products it has on the market and its dwindling pipeline. Analysts have called for the company to specialize more as many of its big pharma brethren have been doing in recent months.
Amgen’s former head of R&D Roger Perlmutter, who is now the driving force of the immunotherapy program at Merck & Co. Inc. as head of its research labs, had been working on a long-term strategy to turn the biotech around and push it further into cancer research.
The hot immuno-oncology field, which uses the body’s own immune cells to fight tumors, has been dominated by Merck, Roche and Bristol-Myers Squibb Co. The big pharmas have been leading the field with their anti-PD-1/L1 drugs, including Merck’s recently approved Keytruda (pembrolizumab) (Also see "Merck’s Keytruda Opens Door, But Combination Trials Could Unlock Efficacy" - Pink Sheet, 8 Sep, 2014.).
Bispecific antibodies are engineered to hit two disease antigens at once. Blinatumomab, which links tumor receptors with activated immune cells, is currently the bispecific molecule furthest along in development, but the technology could have utility in HIV and other diseases (Also see "Is The Time Finally Right For Bispecific Antibodies?" - Pink Sheet, 16 Apr, 2013.).