ABBV-167 / AbbVie - LARVOL DELTA

Pharmaceutical Development Challenges in a Beyond Rule of Five Prodrug: Case Study of ABBV-167, Phosphate Prodrug of Venetoclax. (PubMed, Mol Pharm) - "The prodrug's chemical structural characteristics and loose crystal packing were found to be responsible for the loss of crystallinity during its manufacturing, which in turn led to high solid-state chemical reactivity and poor shelf life stability. The ABBV-167 case exemplifies key CMC development challenges for complex chemical matter such as bRo5 phosphate prodrugs with significant ramifications during drug substance and drug product manufacturing and storage."

Journal

Debate: All Non-FLT3 Mutated AML Patients Above Age 60 with ELN Intermediate or Adverse Risk Should Be Treated with Azacitidine and Venetoclax - YES (LLM Congress 2023) - No abstract available.

Syndax Pharmaceuticals Reports Fourth Quarter 2021 Financial Results and Provides Clinical and Business Update (PRNewswire) - "...Based on discussions with the U.S. Food and Drug Administration (FDA), AUGMENT-101 may serve as the basis for regulatory filings in each of the three distinct populations. The Company expects to receive initial topline data from the trials starting in the first half of 2023, with the potential for the first NDA filing in 2023...The Company expects to initiate three additional trials in the first half of 2022 to assess...anti-leukemic efficacy of SNDX-5613 in combination with venetoclax and azacitidine..."

NDA • New trial • Acute Lymphocytic Leukemia • Leukemia • Oncology

Kura Oncology Reports Preclinical Data Highlighting Synergistic Activity of Menin Inhibitor KO-539 in Combination with Venetoclax (GlobeNewswire) - “The new preclinical data confirm that treatment with KO-539 drives dose-dependent induction of growth inhibition, differentiation and loss of viability of AML cells with KMT2A rearrangements or NPM1 mutations, while also reducing key protein levels such as MEIS1, FLT3 and BCL2 and menin itself. In addition, the new findings show that co-treatment with KO-539 and the BCL2 inhibitor venetoclax induces synergistic activity in patient-derived AML cells expressing KMT2A rearrangements or NPM1 mutations, with or without mutant FLT3 expression, and prolongs survival in an aggressive disseminated model of KMT2A-rearranged, FLT3-mutant AML.”

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Actinium Reports Encouraging Data From Phase 1 Portion Of Actimab-A, Venetoclax Combination Trial (Nasdaq) - “Actinium Pharmaceuticals, Inc. (ATNM) reported data from the phase 1 portion of its Actimab-A and venetoclax combination trial in patients with relapsed or refractory acute myeloid leukemia. Key findings from the study to date include: 67% overall response rate with 2 remissions in patients with a TP53 mutation; and no early mortality in the study to date. One patient achieving remission has been on study for over 230 days and remains in follow-up after previously failing venetoclax HMA therapy before enrolling on Actimab-A study, the company said.”

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Ongoing MDS clinical trials to look out for (YouTube) - "Daniel Pollyea, MD, MS...comments on novel treatments targeting myelodysplastic syndromes (MDS) under development including pevonedistat, a NEDD8-activating enzyme (NAE) inhibitor, and sabatolimab, an anti-TIM-3 antibody. Dr Pollyea additionally highlights venetoclax and magolimab, anti-CD47 monoclonal antibody, which are both undergoing clinical trials. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA."

Interview • Video

Expanding the repertoire for "large small molecules" : Prodrug ABBV-167 efficiently converts to venetoclax with reduced food effect in healthy volunteers. (PubMed, Mol Cancer Ther) - "Additionally, ABBV-167 demonstrated a lower food effect with respect to commercial venetoclax tablets. These data indicate that beyond-rule-of-5 molecules can be successfully delivered to humans via a solubility-enhancing prodrug moiety to afford robust exposures of the parent drug following oral dosing."

Clinical • Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Newly added product (AbbVie Press Release) - P1, Hematological Malignancies

Pipeline update