Flynpovi (eflornithine/sulindac) / Panbela Therap - LARVOL DELTA

Preclinical evaluation of the efficacy of α-Difluoromethylornithine and Sulindac against SARS-CoV-2 infection. (PubMed, bioRxiv) - "The treatment regime was ineffective in suppressing SARS-CoV-2 infection in K18-hACE2 mice. Overall, animal studies demonstrated the protective age- and sex-dependent antiviral efficacy of DFMO and Sulindac against SARS-CoV-2."

Journal • Preclinical • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Infectious Disease • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Solid Tumor • ACE2

A Double Blind Placebo-Controlled Trial of Eflornithine and Sulindac to Prevent Recurrence of High Risk Adenomas and Second Primary Colorectal Cancers in Patients with Stage 0-III Colon or Rectal Cancer, Phase III - Preventing Adenomas of the Colon with Eflornithine and Sulindac (PACES) (SWOG-Fall 2024) - "Accrual Goals A total of 318 patients will be enrolled, 159 to each arm. Summary Statement For the current status of this study, please refer to the Prevention, Screening, and Surveillance chapter."

Clinical • P3 data • Cardiovascular • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Genetic Disorders • Hematological Disorders • Immunology • Inflammatory Bowel Disease • Oncology • Otorhinolaryngology • Peptic Ulcer • Solid Tumor

Panbela Announces Issuance of New Patent in the US and Canada; Patent is for Claims of a Fixed Dose Combination of Eflornithine and Sulindac (GlobeNewswire) - "Panbela Therapeutics, Inc. (OTCQB: PBLA), a clinical-stage biopharmaceutical company developing disruptive therapeutics for the treatment of patients with cancer, today announced an Issue Notification for the US continuation patent US 11,925,613 B2 and Canadian patent CA 3003149 titled 'EFLORNITHINE AND SULINDAC, A FIXED DOSE COMBINATION FORMULATION'. These patents claim a novel composition of a fixed dose combination of eflornithine and sulindac, which is called Flynpovi....The patents are valid until 2036, have issued in the US, Australia, Mexico, Taiwan, and Chile. The application is under review in additional countries."

Patent • Oncology

A Double Blind Placebo-Controlled Trial of Eflornithine and Sulindac to Prevent Recurrence of High Risk Adenomas and Second Primary Colorectal Cancers in Patients with Stage 0-III Colon or Rectal Cancer, Phase III - Preventing Adenomas of the Colon with Eflornithine and Sulindac (PACES) (SWOG-Spring 2024) - "Accrual Goals A total of 318 patients will be enrolled, 159 to each arm. Summary Statement For the current status of this study, please refer to the Prevention and Epidemiology chapter."

Clinical • P3 data • Cardiovascular • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Genetic Disorders • Hematological Disorders • Immunology • Inflammatory Bowel Disease • Oncology • Otorhinolaryngology • Peptic Ulcer • Solid Tumor

Preventive effects of chemical drugs on recurrence of colorectal adenomas: systematic review and Bayesian network meta-analysis. (PubMed, Eur J Gastroenterol Hepatol) - "DFMO + Sulindac is more effective in reducing the recurrence of CRAs but has a high risk of adverse events. Considering drug safety, tolerance, and compliance, berberine has a brighter prospect of clinical development. However, further studies are needed to verify our findings."

Journal • Retrospective data • Review • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Eflornithine for chemoprevention in the high-risk population of colorectal cancer: a systematic review and meta-analysis with trial sequential analysis. (PubMed, Front Oncol) - "Subgroup analysis demonstrates that, depending on the drug treatment regimen (DFMO+ Aspirin/DFMO+ Sulindac), the combination of DFMO and aspirin exhibits an effect comparable to a placebo in diminishing the occurrence of new adenomas in patients with a history of advanced colorectal tumors...This meta-analysis indicates that the existing randomized controlled trials are adequate to ascertain the efficacy of DFMO combination therapy in diminishing the incidence of recurrent adenomas in patients who have previously encountered advanced colorectal tumors. However, further clinical trials need to be conducted to evaluate the optimum dosage and treatment course of prophylactic implementation of DFMO combination therapy in high-risk populations."

Retrospective data • Review • Colorectal Cancer • Gastrointestinal Cancer • Genetic Disorders • Oncology • Solid Tumor

A Double-Blind Placebo-Controlled Trial of Eflornithine and Sulindac to Prevent Recurrence of High Risk Adenomas and Second Primary Colorectal Cancers in Patients with Stage 0-III Colon or Rectal Cancer, Phase III – Preventing Adenomas of the Colon with Eflornithine and Sulindac (PACES). (SWOG-Fall 2023) - "Accrual Goals A total of 318 patients will be enrolled, 159 to each arm. Summary Statement For the current status of this study, please refer to the Prevention and Epidemiology chapter."

Clinical • P3 data • Cardiovascular • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Genetic Disorders • Hematological Disorders • Immunology • Inflammatory Bowel Disease • Oncology • Otorhinolaryngology • Peptic Ulcer • Solid Tumor

A Double-Blind Placebo-Controlled Trial of Eflornithine and Sulindac to Prevent Recurrence of High Risk Adenomas and Second Primary Colorectal Cancers in Patients with Stage 0-III Colon or Rectal Cancer, Phase III – Preventing Adenomas of the Colon with Eflornithine and Sulindac (PACES). (SWOG-Fall 2023) - "Accrual Goals A total of 318 patients will be enrolled, 159 to each arm. Summary Statement For the current status of this study, please refer to the Prevention and Epidemiology chapter."

Clinical • P3 data • Cardiovascular • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Genetic Disorders • Hematological Disorders • Immunology • Inflammatory Bowel Disease • Oncology • Otorhinolaryngology • Peptic Ulcer • Solid Tumor

A Double Blind Placebo-Controlled Trial of Eflornithine and Sulindac to Prevent Recurrence of High Risk Adenomas and Second Primary Colorectal Cancers in Patients with Stage 0-III Colon or Rectal Cancer, Phase III – Preventing Adenomas of the Colon with Eflornithine and Sulindac (PACES). (SWOG-Fall 2023) - "Accrual Goals A total of 318 patients will be enrolled, 159 to each arm. Summary Statement For the current status of this study, please refer to the Prevention and Epidemiology chapter."

Clinical • P3 data • Cardiovascular • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Genetic Disorders • Hematological Disorders • Immunology • Inflammatory Bowel Disease • Oncology • Otorhinolaryngology • Peptic Ulcer • Solid Tumor

PACES: S0820, Adenoma and Second Primary Prevention Trial (clinicaltrials.gov) - P3 | N=354 | Active, not recruiting | Sponsor: SWOG Cancer Research Network | Recruiting ➔ Active, not recruiting | N=1340 ➔ 354

Enrollment change • Enrollment closed • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Chemoprevention of Colon Cancer by DFMO, Sulindac, and NO-Sulindac Administered Individually or in Combinations in F344 Rats. (PubMed, Cancers (Basel)) - "In addition, enhancement of p21, Bax, and caspases; downregulation of Ki-67, VEGF, and β-catenin; and modulation of iNOS, COX-2, and ODC activities in colonic tumors were observed. These observations show that a lower-dose of DFMO and Sulindac significantly enhanced CRC chemopreventive efficacy when compared to NO-Sulindac alone, and the combination of DFMO and NO-Sulindac was modestly efficacious as compared to DFMO alone."

Journal • Preclinical • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CDKN1A • CTNNB1

Panbela Announces PACES S0820 Phase III Trial Passes Pre-Planned Futility Analysis (GlobeNewswire) - "Panbela Therapeutics, Inc...announced the SWOG Cancer Research Network’s PACES S0820 Phase III trial passed a single planned futility analysis and will continue. The trial...is designed to evaluate the combination of eflornithine and sulindac in reducing a three-year event rate of adenomas and second primary colorectal cancers in patients previously treated for Stages 0 through III colon or rectal cancer."

Trial status • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Rectal Cancer • Solid Tumor

Panbela Announces Clinical Trial with Moffitt Cancer Center for Phase I/II Program in STK11 Mutant Non-Small Cell Lung Cancer (GlobeNewswire) - "'There is a huge unmet need for new therapies for STK11 mutant non-small cell lung cancer patients, given their low survival rates. We know that STK11 mutant tumors have reduced levels of T cells that direct immune surveillance, and they can avoid immune detection. We are excited to partner with Panbela to determine if modulating polyamines can restimulate the immune system to target these hard-to-treat tumors.' said Jhanelle Gray, M.D."

Media quote

Panbela Announces Clinical Trial with Moffitt Cancer Center for Phase I/II Program in STK11 Mutant Non-Small Cell Lung Cancer (GlobeNewswire) - "Panbela Therapeutics, Inc...announced it has entered into a clinical trial agreement with Moffitt Cancer Center for a Phase I/II program in STK11 mutant non-small cell lung cancer (NSCLC). The initial goal of the Phase I trial will be to ascertain the maximum tolerated dose of eflornithine, while evaluating efficacy and then moving into a Phase II efficacy trial. We anticipate data from the Phase I trial by the end of this year with a look to start the Phase II trial at the end of the year or early 2024."

New P2 trial • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Panbela Announces New Research Agreement with Johns Hopkins University School of Medicine (GlobeNewswire) - "Panbela Therapeutics, Inc...today announced a new research agreement with the Johns Hopkins University School of Medicine. The collaboration is intended to expand the development of Panbela’s investigative agent ivospemin (SBP-101), including activity in models of ovarian and other cancer types, further evaluations into mechanism of action, and potential combination with CPP-1X and standard of care agents."

Licensing / partnership • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

The efficacy of chemopreventive agents on the incidence of colorectal adenomas: A systematic review and network meta-analysis. (PubMed, Prev Med) - "Compared to placebo, the combination of difluoromethylornithine (DFMO) + Sulindac (RR 0.24, CrI 0.10-0.55) demonstrated a protective effect, while aspirin had a RR of 0.77 (CrI 0.60-1.00), celecoxib 800 mg had a RR of 0.56 (CrI 0.31-1.01) and metformin had a RR of 0.56 (CrI 0.22-1.39). Our results suggest that select CPAs may be efficacious in preventing the development of adenomas. Further studies are needed to identify those patients most likely to benefit and the minimum effective dosages of CPAs."

Journal • Retrospective data • Review • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

PACES: S0820, Adenoma and Second Primary Prevention Trial (clinicaltrials.gov) - P3 | N=1340 | Recruiting | Sponsor: Southwest Oncology Group | Trial completion date: Jul 2029 ➔ Feb 2032 | Trial primary completion date: Jul 2025 ➔ Feb 2027

Trial completion date • Trial primary completion date • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Combination of Sulindac and Eflornithine Delays the Need for Lower Gastrointestinal Surgery in FAP Patients: Post-Hoc Analysis of a Randomized Clinical Trial. (PubMed, Dis Colon Rectum) - "Eflornithine-sulindac combination therapy was superior to either drug alone in delaying or preventing the need for lower gastrointestinal tract surgery in patients with familial adenomatous polyposis. See Video Abstract at http://links.lww.com/DCR/B658 ."

Clinical • Journal • Retrospective data • Gastrointestinal Disorder • Genetic Disorders

Updates in chemoprevention research for hereditary gastrointestinal and polyposis syndromes. (PubMed, Curr Treat Options Gastroenterol) - "In the FAPEST trial, the combination of erlotinib+sulindac (compared to placebo) met its primary outcome of decreased duodenal polyp burden...Two randomized trials in FAP patients examining combination regimens (celecoxib+DFMO and sulindac+DFMO) failed to meet their primary endpoints...Finally, a randomized trial found curcumin (vs placebo) to have no benefit in reducing colorectal polyp count or size in patients with FAP. Progress in developing new and more effective preventive options for patients with hereditary gastrointestinal syndromes continues to be made through the efforts of investigators conducting chemoprevention research."

Journal • Colonic Polyps • Gastrointestinal Cancer • Gastrointestinal Disorder • Genetic Disorders • Oncology • Solid Tumor

"Nice study.... but polyp size >5mm is not an important clinical endpoint. I would prefer sulindac/eflornithine 😉" (@RHuneburg)

Clinical

Trial of Eflornithine Plus Sulindac in Patients With Familial Adenomatous Polyposis (FAP) (clinicaltrials.gov) - P3; N=150; Recruiting; Sponsor: Cancer Prevention Pharmaceuticals, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Colorectal Cancer • Genetic Disorders • APC

Trial of Eflornithine Plus Sulindac in Patients With Familial Adenomatous Polyposis (FAP) (clinicaltrials.gov) - P3; N=150; Recruiting; Sponsor: Cancer Prevention Pharmaceuticals, Inc.

Clinical • New P3 trial • Colorectal Cancer • Genetic Disorders • APC

Trial of Eflornithine Plus Sulindac in Patients With Familial Adenomatous Polyposis (FAP) (clinicaltrials.gov) - P3; N=150; Recruiting; Sponsor: Cancer Prevention Pharmaceuticals, Inc.; Initiation date: May 2013 ➔ Oct 2013

Clinical • Trial initiation date • Colorectal Cancer • Genetic Disorders • APC

Trial of Eflornithine Plus Sulindac in Patients With Familial Adenomatous Polyposis (FAP) (clinicaltrials.gov) - P3; N=171; Completed; Sponsor: Cancer Prevention Pharmaceuticals, Inc.; Active, not recruiting ➔ Completed; Trial completion date: Jun 2019 ➔ Mar 2019

Clinical • Trial completion • Trial completion date • Colorectal Cancer • Gastrointestinal Cancer • Genetic Disorders • Solid Tumor • APC

Trial of Eflornithine Plus Sulindac in Patients With Familial Adenomatous Polyposis (FAP) (clinicaltrials.gov) - P3; N=171; Active, not recruiting; Sponsor: Cancer Prevention Pharmaceuticals, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Colorectal Cancer • Genetic Disorders • APC