Trizell Ltd. announces Phase 3 pivotal study of interferon alfa-2b gene therapy in malignant pleural mesothelioma

LONDON, March 20, 2019 /PRNewswire/ -- Trizell Ltd (Trizell) announces today that it has opened a Phase 3 Study of its novel gene therapy TR002, an adenovirus-mediated interferon alfa 2b, in patients with malignant pleural mesothelioma (MPM) who have failed first-line standard of care chemotherapy. TR002 is given to trigger the pleiotropic anti-tumour effects of interferon, a naturally occurring protein the body uses to fight cancer, and is followed by gemcitabine chemotherapy. This study will include sites in the United States, Europe, Australia, and Russia.

Malignant pleural mesothelioma is an aggressive and devastating form of cancer affecting the outer (pleural) membrane of the lungs. The disease is usually triggered by inhalation of asbestos fibres that slowly make their way from the alveoli to the outer surface of the lung in the pleural cavity. The fibres then induce a cancer which grows on the outside of the lung into the pleural space, eventually invading surrounding thoracic tissues leading to death. There is a clear association between occupational or environmental asbestos and mineral fibre exposure and MPM development.

A previous Phase 2 study of TR002 at the Abramson Cancer Center included 40 MPM patients who were newly diagnosed or failed standard chemotherapy (Pemetrexed/ Platin) showed an overall disease control rate of 87.5%. The second line treatment cohort showed an almost doubling of median survival time compared to historical study controls (17 months vs. 9 months) with approximately 25% of patients living at least 2 years and approximately 20% at least 3 years.

MPM prognosis is poor and following failure of standard of care first line treatment, median life expectancy is around 9 months, with very few cases surviving past 18 months. With a prevalence of around 200,000 cases worldwide, there are around 3000 and 5000 new cases diagnosed every year in the EU and US alone. Dust from the September 11th attacks in New York is predicted to cause a rise in the number of future cases in the US, although the extent of the future rise is currently unclear. 

"This is an exciting trial. The results that we noted in our previous study showed significant prolongation of life expectancy and particularly so for about 25 percent of these refractory patients who have gone on to live two and in some cases three years and more," said Daniel H. Sterman, MD, Director of the Multidisciplinary Pulmonary Oncology Program at NYU Langone Health. "We will work hard to get this potentially ground-breaking clinical trial completed."

The Phase 3 study is an open-label, randomized, parallel group study in up to approximately 300 patients who have failed chemotherapy. TR002 is given by catheter directly into the pleural cavity as a single dose of 3 x 10¹¹ viral particles. Gemcitabine chemotherapy commences 14 days later and continues until disease progression.

"It is very exciting to see a therapeutic approach developed at the University of Pennsylvania being moved to an international, randomized trial, as it is a career milestone for any academic researcher to see their work tested in this way," said Steven M. Albelda, MD, William Maul Measey Professor of Medicine, Perelman School of Medicine, University of Pennsylvania.

TR002 was pioneered by Drs. Albelda and Sterman, and by Dr. Evan W. Alley, MD, PhD, whose current appointment is at Cleveland Clinic Florida but who was involved in the trial during his time at Penn.  

About TR002 
TR002 (nadofaragene firadenovec) is an investigational gene therapy consisting of an adenovirus containing the gene interferon alfa-2b. It is administered by catheter into the pleural cavity, where the virus enters the cells lining the pleural cavity. Inside the cells, the virus breaks down leaving the active gene to do its work. The internal gene/DNA machinery of the cells picks up the gene and translates its DNA sequence, resulting in the cells secreting high quantities of interferon alfa-2b protein, a naturally occurring protein the body uses to fight cancer. This novel gene therapy approach turns the patient's own pleural cavity cells into multiple interferon microfactories, enhancing the body's natural defences against the cancer.

About Malignant Pleural Mesothelioma
Malignant pleural mesothelioma is usually triggered by inhalation of asbestos fibres. These slowly make their way from the alveoli to the outer surface of the lung in the pleural cavity where they induce a cancer which grows on the outside of the lung into the pleural space, eventually invading surrounding thoracic tissues leading to death. Prognosis is poor and following failure of standard of care first-line treatment, median life expectancy is around 9 months, with very few cases surviving past 18 months.

WHO estimates that 43,000 people die of MPM each year; annually in North America, Western Europe, Japan, and Australia, there are 10,000 cases each year¹. With the passage of the Clean Air Act, asbestos use was banned in the US in 1970², and the incidence of mesothelioma in the US was predicted to steadily decline. However, dust from the September 11^th attacks in New York is predicted to cause a rise in the number of future cases although the extent of the future rise is currently unclear³. In contrast, asbestos use continued in Australia until 2003 and in Europe until 2005. As a result, the incidence of mesothelioma in European countries continues to rise and is projected to peak in 2020 and may account for as many as 250,000 European deaths in the next 35 years. In 2020, it is estimated over 18,000 Australian cases will be diagnosed⁴.

About Trizell Ltd
Trizell Ltd (The Company) is a specialist gene therapy company operating in the Advanced Therapy Medicinal Products (ATMP) area. Trizell has a strong late-stage portfolio of products in clinical trials with its own R and D and state of the art commercial manufacturing facilities in Finland and the UK. The Company is part of the Trizell SA Group.

¹ Delgermaa, V., Takahashi, K., Park, E. K., Le, G. V., Hara, T., & Sorahan, T. (2011). World Health Assembly». Bulletin of the World Health Organization, 89, 716-724C.
² US Environmental Protection Agency. Evolution of the Clean Air Act. Retrieved March 6, 2019, from https://www.epa.gov/clean-air-act-overview/evolution-clean-air-act.
³ Asbestos.com. Asbestos, 9/11 and the World Trade Centre. Retrieved March 6, 2019, from https://www.asbestos.com/world-trade-center/.
⁴ Goudar, R. K. (2008). Review of pemetrexed in combination with cisplatin for the treatment of malignant pleural mesothelioma. Therapeutics and clinical risk management, 4(1), 205.

SOURCE Trizell Ltd.