Amgen’s receives FT based on 10 patients. While we’re on the verge of getting BTD w pozi in Dec 2018, back in early 2017, Dr Raj used to say that we could possibly have enough mature data by the end of 2017 to apply for BTD. Well, since it’s now the end of 2018, you would think that Dr Raj told a lie or at least a gross exaggeration. But after reading today that Amgen got Fast Track based on 7 out of 10 responses after a 7.5m readout, I don’t believed he lied to us. But since this is the end of 2018 and not 2017 maybe there was a little exaggeration;). From Amgen's PR yesterday
ASH Abstract #1010: Treatment with AMG 420, an anti-B-Cell Maturation Antigen (BCMA) Bispecific T-cell Engager (BiTE®) Antibody Construct, Induces Minimal Residual Disease (MRD) Negative Complete Responses in Relapsed and/or Refractory (R/R) Multiple Myeloma (MM) Patients: Results of a First-in-Human (FIH) Phase 1 Dose Escalation Study The data shared at ASH were the first presentation of all endpoints from this Phase 1 dose-escalation trial of AMG 420 in patients with relapsed and/or refractory multiple myeloma. The objectives of the study included assessment of safety, tolerability and anti-tumor activity of AMG 420 per International Myeloma Working Group 2006 Uniform Response Criteria for Multiple Myeloma. In the study, 42 patients with relapsed and/or refractory multiple myeloma who had progression after at least two prior lines of treatment (including a proteasome inhibitor and an immunomodulatory imide drug) received AMG 420 at varying doses [0.2 to 800 µg/day (d)]. AMG 420 induced clinical responses in 13 patients, including complete responses (CR) in seven patients. Four patients treated at the 400 µg/d dose achieved minimal residual disease (MRD) negative complete responses, meaning that no cancer cells were detectable in the bone marrow. The objective response rate at 400 µg/d was 70 percent (seven of 10 patients), with six patients still responding up to 7.5 months. One dose-limiting toxicity was observed up to the 400 µg/d dose (peripheral polyneuropathy, which improved to baseline after intravenous immunoglobulin and corticosteroid treatment). Of those patients with serious adverse events (AEs) (n=20, 48 percent), 17 required hospitalization and four had prolonged hospitalization. Serious AEs included infections (n=12), peripheral polyneuropathy (n=2), and one each of liver failure, cardiac failure, edema, biliary obstruction, spinal cord compression, renal failure and weight loss. Treatment-related serious AEs included polyneuropathy (n=2, both grade 3) and edema (n=1, grade 3). Cytokine release syndrome (CRS) was seen in 16 patients (grade 1, n=13; grade 2, n=2; grade 3, n=1). In this study, 800 µg/d was determined to not be tolerable, as two out of the three patients treated at this dose experienced dose-limiting toxicities. Two patients died during the course of the study from AEs not considered treatment-related. One patient died after the first cycle of treatment from acute respiratory distress due to concurrent flu and aspergillosis. The second patient died from liver failure secondary to a viral infection during the course of treatment. "These first-in-human data of a BCMA-targeting BiTE® immunotherapy showed encouraging evidence of AMG 420 activity, with no major toxicities up to the 400 µg/d dose in patients with relapsed and/or refractory multiple myeloma who received a median of four prior therapies," said Max S. Topp, M.D., professor, Hospital of Wuerzburg, Germany and AMG 420 clinical study investigator. "Despite recent treatment advances, multiple myeloma continues to be a disease characterized by cycles of relapse and recurrence requiring additional therapies to help control the disease." Additionally, AMG 420 was granted Fast Track Designation by the U.S. Food and Drug Administration (FDA). Fast track is a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious conditions.
So just thinking (musings here), when pozi receives BTD for egfrExon20in in 2nd/3rd line this month (99% probability in IMHO) from a cohort of 40 or so patients, will this loosen the spigot for BTD for her2Exon20in in 2nd/3rd line w less pts(eg 10?). Seeing Amgen get Fast Tract just on data from just 10 pts makes me start thinking that way. Ditto on first line too. Back in post 2347, I posted the general criteria for BTD and FT from a FDA presentation. It almost seems like interchangeable criteria.
Fast Track Criteria: A drug that: • Is intended to treat a serious condition AND nonclinical or clinical data demonstrate the potential to address unmet medical need
Breakthrough Therapy Program Criteria A drug that treats: • Serious condition, AND • Preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on one or more clinically significant endpoints
Priority Review Criteria: An application for a drug : • That treats a serious condition AND, if approved, would provide a significant improvement in safety or effectiveness
I should also note, regarding Amgen's drug, in all the cohorts (n=42) not just the dose receiving the FT dose, that this drug has series AEs.
Of those patients with serious adverse events (AEs) (n=20, 48 percent), 17 required hospitalization and four had prolonged hospitalization.
Almost makes pozi's AEs a walk in the park, and still Amgen's drug got Fast Track. When you have an unmet medical need you really have no other choice.
AI
