apatorsen (OGX-427) / Achieve Life Sciences - LARVOL DELTA

HSP27 Promotes Activation of Parietal Epithelial Cells and Crescent Formation in Crescentic Glomerulonephritis (KIDNEY WEEK 2024) - "Targeting of HSP27 with the antisense oligonucleotide (OGX-427) results in reduced development of crescents in the NTS model... Taken together, our data highlight a role for HSP27 in the development of crescent lesions and pave the way for innovative therapeutic approaches for CrGN patients."

Glomerulonephritis • Lupus Nephritis • Nephrology • Oncology • CD44

LBA02-09 EMBARK: A Phase 3 Randomized Study of Enzalutamide or Placebo Plus Leuprolide Acetate and Enzalutamide Monotherapy in High-risk Biochemically Recurrent Prostate Cancer. (PubMed, J Urol) - P3 | "In pts with high-risk BCR, enza + ADT and enza mono demonstrated a statistically significant and clinically meaningful improvement in MFS vs pbo + ADT. The safety profile of enza was consistent with results from previous clinical studies."

Journal • Monotherapy • P3 data • Fatigue • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Phase II, randomised, open-label study of Gemcitabine/Carboplatin first-line chemotherapy in combination with or without the antisense oligonucleotide Apatorsen (OGX-427) in advanced squamous cell lung cancers (ESMO 2017) - P2; "This trial failed to demonstrate a benefit for adding apatorsen to standard chemotherapy in newly diagnosed SCC."

Combination therapy • Late-breaking abstract • Non Small Cell Lung Cancer

Borealis-2: A randomized phase II study of OGX-427 (apatorsen) plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial cancer (mUC) (Hoosier Cancer Research Network GU12-160). (ASCO-GU 2017) - P2; "In this platinum-pretreated population of advanced UC, adding OGX-427 to D provided a statistically significant improvement in OS and is worthy of further investigation in previously treated metastatic UC pts."

Clinical • P2 data • Prostate Cancer

PACIFIC trial: A randomized phase II study of apatorsen and abiraterone in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC) who have had PSA progression while receiving abiraterone (ABI). (ASCO-GU 2017) - P2; " mCRPC patients with PSA-only progression on ABI + prednisone (P) 10-20 mg daily were randomized to continuing ABI + P (Control Arm) or ABI + P with Apatorsen 600 mg IV x 3 loading doses then 800 mg IV weekly (Study Arm). Apatorsen may have activity when added to abiraterone for mCRPC patients progressing on abiraterone. Establishing predictors of response should be a priority for future studies."

Clinical • P2 data • Biosimilar • Oncology • Prostate Cancer • Venous Thromboembolism

DDX5 mRNA-targeting Antisense Oligonucleotide as a new promising therapeutic in combating Castration-Resistant Prostate Cancer. (PubMed, Mol Ther) - "The Heat Shock Protein 27 (Hsp27) has emerged as a principal factor of the Castration-Resistant Prostate Cancer (CRPC) progression, also, an Antisense Oligonucleotide (ASO) against Hsp27 (OGX-427 or Apatorsen) has been assessed in different clinical trials...We first present the interactions of DDX5 and the Ku70/80 heterodimer and the transcription factor IIH (TFIIH), thereby uncovering DDX5 roles in different DNA repair pathways. Collectively, our study highlights critical functions of DDX5 contributing to CRPC progression and provides preclinical proof-of-concept that a combination of ASO-directed DDX5 inhibition with a DNA damage-inducing therapy can serve as a highly potential novel strategy to treat CRPC."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • DDX5

A Review on the Efficacy and Safety of Nab-Paclitaxel with Gemcitabine in Combination with Other Therapeutic Agents as New Treatment Strategies in Pancreatic Cancer. (PubMed, Life (Basel)) - "The seven therapeutic agents were ibrutinib, necuparanib, tarextumab, apatorsen, cisplatin, enzalutamide, and momelotinib. The triple regimen is emerging as the first-line option for patients with pancreatic cancer, albeit with some limitations. Thus, further studies of this regimen are recommended."

Combination therapy • Journal • Review • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A Randomized, Double-Blinded, Phase II Trial of Carboplatin and Pemetrexed with or without Apatorsen (OGX-427) in Patients with Previously Untreated Stage IV Non-Squamous-Non-Small-Cell Lung Cancer: The SPRUCE Trial. (PubMed, Oncologist) - "This randomized, double-blinded, phase II trial evaluated the efficacy of carboplatin and pemetrexed plus either apatorsen, an antisense oligonucleotide targeting heat shock protein 27 mRNA, or placebo in patients with previously untreated metastatic nonsquamous non-small cell lung cancer (NSCLC). The addition of apatorsen to carboplatin and pemetrexed was well tolerated but did not improve outcomes in patients with metastatic nonsquamous NSCLC cancer in the first-line setting."

Clinical • Journal • P2 data • Fatigue • Hematological Disorders • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Thoracic Cancer

Development and Clinical Applications of Antisense Oligonucleotide Gapmers. (PubMed, Methods Mol Biol) - "In addition, volanesorsen was conditionally approved in the EU for the treatment of adult patients with familial chylomicronemia syndrome (FCS) in 2019. Many others are being tested in clinical trials or under preclinical development. This chapter will cover the development of mipomersen and inotersen in clinical trials, along with advancement in gapmer treatments for cancer, triglyceride-elevating genetic diseases, Huntington's disease, myotonic dystrophy, and prion diseases."

Clinical • Journal • Amyloidosis • CNS Disorders • Dyslipidemia • Genetic Disorders • Huntington's Disease • Hypertriglyceridemia • Lipodystrophy • Metabolic Disorders • Movement Disorders • Muscular Dystrophy • Myotonic Dystrophy • Oncology

Battling resistance mechanisms in antihormonal prostate cancer treatment: Novel agents and combinations. (PubMed) - "The wide variety in upcoming systemic agents underlines the molecular heterogeneity of castration-resistant PCa. This article reviews antihormonal therapy in PCa and resistance mechanisms and focuses on novel and upcoming agents currently in clinical testing."

Review • Biosimilar • Oncology • Prostate Cancer

The Spruce clinical trial: Double-blind randomized phase II trial of carboplatin and pemetrexed +/- apatorsen in patients with previously untreated stage IV non-squamous non-small-cell lung cancer (ASCO 2016) - P2, N=155; NCT01829113; "Median PFS was A 6.0 months (mo) vs PL 4.9 mo; HR (2-sided 95% CI) was 0.922 (0.634, 1.340), p = 0.6687. Objective response rate: A 26% vs PL 31%. Median duration of treatment was A 15 wks vs PL 19 wks."

P2 data • Non Small Cell Lung Cancer • Oncology

OncoGenex announces update on phase 2 SPRUCE trial in previously untreated metastatic non-small cell lung cancer (Oncogenex Pharmaceuticals Press Release) - P2, N=155; SPRUCE; "OncoGenex Pharmaceuticals...announced...that data from the Phase 2 Spruce trial evaluating the combination of apatorsen with carboplatin and pemetrexed in patients with untreated metastatic non-small cell lung cancer (NSCLC) did not reach the statistical significance required to demonstrate a progression-free survival (PFS) benefit. A potential PFS benefit was observed in patients with high baseline serum Hsp27 status when treated with apatorsen. The study is ongoing and overall survival results are expected in the second half of 2016."

Anticipated P2 data • P2 data • Non Small Cell Lung Cancer • Oncology

"Great presenting @OncoGenexPharma OGX-427 + data in bladder cancer with friends and the PreZ of @ASCO @drbrucejohnson #GU17" - DrChoueiri

Clinical • Twitter

Bortezomib promotes apoptosis of multiple myeloma cells by regulating HSP27. (PubMed, Mol Med Rep) - "The changes of HSP27 after conventional vincristine, doxorubicin and dexamethasone (VAD) chemotherapy, and bortezomib plus VAD were compared...HSP27 was positively correlated with Bcl‑2 expression and negatively correlated with Bax expression in U266 cells. In conclusion, bortezomib promotes the apoptosis of MM cells, potentially by downregulating the expression of HSP27, providing a potential novel target for the clinical treatment of multiple myeloma."

Journal

Urothelial carcinoma: Apatorsen plus docetaxel does not provide significant value (YouTube) - "Petros Grivas, MD, PhD...discusses a trial comparing apatorsen plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial carcinoma (NCT01780545). Dr Grivas points out that it was an important study contributing to the literature, but that the combination tested did not provide enough efficacy."

Interview • Video

Sonpavde provides overview of new research that advances urothelial cancer treatments (Targeted Oncology) - "During an interview with Targeted Oncology, Sonpavde...highlights the extensive research around checkpoint inhibition and chemotherapy combinations and how these regimens are advancing bladder cancer treatment."

Interview

Apatorsen plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial carcinoma (Borealis-2). (PubMed, Br J Cancer) - "A/D met its predefined OS end point in patients with platinum-refractory mUC in this phase II trial. This trial is hypothesis generating requiring further study before informing practice."

Journal