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Pexastimogene Devacirepvec (Pexa-Vec) for Hepatocellular Carcinoma – First Line NIHRIO (HSRIC) ID: 4760 NICE ID: 9538

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Pexastimogene Devacirepvec (Pexa-Vec) for Hepatocellular Carcinoma – First Line NIHRIO (HSRIC) ID: 4760 NICE ID: 9538 NIHR Innovation Observatory Evidence Briefing: September 2017 Pexastimogene devacirepvec (pexa-vec) for hepatocellular carcinoma – first line NIHRIO (HSRIC) ID: 4760 NICE ID: 9538 LAY SUMMARY Liver cancer was the 17th most diagnosed cancer in the UK in 2014. This type of cancer develops from the main liver cells, called hepatocytes. Hepatocellular carcinoma is more common in people who have long-term damage to the liver tissues (cirrhosis). It is also more likely to develop in men than in women and it becomes more common as people get older. Pexastimogene devacirepvec is under development for the first line treatment of advanced hepatocellular carcinoma. The drug is an engineered virus with a gene that promotes the body’s natural response to cancerous cells in the liver. This treatment is administered by injection directly into the cancerous cells in the liver or through the veins. It is designed to selectively target and destroy cancer cells through three different ways: direct destruction of the cancer cells, reduction of the blood supply to tumours and the stimulation of the body’s defense against cancer cells. If licensed, pexastimogene devacirepvec may offer an additional treatment option for patients. Currently, there are few treatment options for advanced hepatocellular carcinoma patients, with only one drug, sorafenib, approved for the first line treatment of advanced hepatocellular carcinoma. This briefing is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes or commissioning without additional information. This briefing presents independent research funded by the National Institute for Health Research (NIHR). The views expressed1 are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health. TARGET GROUP Advanced Hepatocellular carcinoma (HCC) – first line, not eligible for locoregional therapies. TECHNOLOGY DESCRIPTION Pexastimogene devacirepvec (Pexa-vec; JX-594) is under development for the treatment of Hepatocellular carcinoma (HCC). Pexa-vec is a thymidine kinase-deleted vaccinia virus expressing human GM-CSF (hGM-CSF) with oncolytic activity. It may selectively infect and lyse tumour cells. The deletion of the thymidine kinase gene increases the tumour selectivity of vaccinia by limiting viral replication to transformed cells. hGM-CSF expression by this agent may help recruit antigen processing cells, such as dendritic cells and macrophages, to virally infected tumour cells, initiating a systemic anti-tumoural immune response. It also selectively replicates and destroys cancer cells with epidermal growth factor receptor/ ras pathway activation.1 Existing treatment options for HCC are liver resection and lobectomy (surgery) to remove the tumour and the surrounding tissues in the liver, liver transplantation, and locoregional therapies including radio frequencey ablation (RFA) and transarterial chemotherapy embolization (TACE) to kill cancer cells.2 Sorafenib is the only drug that is currently approved for the first line treatment of advanced HCC in patients not eligible for, or after these locoregional therapies.3 In the ongoing phase III trial (PHOCUS), subjects in the experimental arm receive pexastimogene devacirepvec as 3 bi-weekly intratumoural injections of 1e9 pfu (plaque forming units) at day 1 and during weeks 2 and 4, followed by sorafenib (taken orally) starting at week 6. Subjects in the control arm receive 400 mg of sorafenib, twice daily starting on day 1.4 Pexastimogene devacirepvec is also under development for the following indications:5 Breast cancer Soft tissue sarcoma Several solid tumours Renal cell carcinoma INNOVATION and/or ADVANTAGES If licensed, pexastimogene devacirepvec may offer an additional treatment option for patients with HCC. This treatment is advantageous in that it is designed to selectively target and destroy cancer cells. Currently, there are few first line treatment options for advanced HCC patients, with only one drug, sorafenib, approved for the treatment of HCC. With a low five-year survival rate, especially for patients diagnosed at later stages of disease, and limited available therapies, new treatments are urgently needed.6 DEVELOPER Transgene SA and SillaJen Inc. 2 PATIENT GROUP BACKGROUND Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, which develops from the main liver cells, called hepatocytes.7 Most patients with HCC have liver cirrhosis, which develops following long periods of chronic liver disease. Cirrhosis is characterized by a decrease in hepatocyte proliferation, indicating an exhaustion of the regenerative capacity of the liver, and results in an increase in fibrous tissue and a destruction of liver cells, which may ultimately lead to the development of cancerous nodules. Half of all cases of HCC are associated with hepatitis B virus infection, with a further 25% associated with hepatitis C virus. Other risk factors for developing HCC include: alcoholic liver disease, non- alcoholic steatohepatitis, intake of aflatoxin-contaminated food, diabetes and obesity.8 Liver cancer is much more likely to develop in men than in women; one in 105 men and one in 195 women will be diagnosed with liver cancer during their lifetime. More than 44% of liver cancer cases in the UK each year are diagnosed in people aged 75 and over with the highest incidence rates in people aged 85-89 (data from 2012-2014).9 The symptoms of liver cancer may include: weight loss, a swollen abdomen, jaundice, loss of appetite over a period of a few weeks, being sick, feeling full or bloated after eating, even after a small meal, itching, a sudden worsening of health in somebody with known chronic hepatitis or cirrhosis, a high temperature and sweating. 10 HCC is usually diagnosed using a combination of blood tests (liver function tests, urea and electrolytes, tumour markers – particularly alpha fetoprotein), ultrasound, CT or MRI scans, biopsy (of liver tumour tissue) and laparoscopic investigation.11 Treatment and survival rates depend on the cancer stage at diagnosis. In relation to all stages of the disease, for adults diagnosed with liver cancer in England, almost 35 out of 100 people (almost 35%) will survive their cancer for 1 year or more after diagnosis; approximately 10 in 100 people (more than 10%) will survive their cancer for 5 years or more after they are diagnosed.12 The symptoms of HCC in addition to the side-effects of treatment may significantly impact the quality of life of individuals with the condition, who may experience pain, fatigue, diarrhea and loss of appetite. Nine out of ten patients reported experiencing pain over their HCC treatment course in a qualitative analysis.13 CLINICAL NEED and BURDEN OF DISEASE In 2014, liver cancer was the seventeenth most common cancer in the UK.9 Incidence rates for liver cancer are projected to rise by 38% in the UK between 2014 and 2035, to 15 cases per 100,000 people by 2035.9 There were 5,550 new cases of this type of cancer, accounting for 2% of total cancer cases in UK, during the same year.9 In 2015-16, there were 4,502 hospital admissions, 6,981 finished consultant episodes and 22,033 bed days due to malignant neoplasm: liver cell carcinoma (C22.0) in England.14 3 PATIENT PATHWAY RELEVANT GUIDANCE NICE GUIDANCE NICE Technology appraisal guidance in development. Regorafenib for previously treated unresectable hepatocellular carcinoma (ID991). Expected date of issue to be confirmed. NICE Technology appraisal guidance in development. Lenvatinib for untreated advanced unresectable hepatocellular carcinoma (ID1089). Expected date of issue to be confirmed. NICE Technology appraisal guidance in development. Hepatocellular carcinoma (advanced and metastatic) – sorafenib (first line) (review of TA189) (ID1012) – CDF rapid reconsideration process. Expected date of issue to be confirmed. NICE Technology appraisal guidance in development. Nivolumab for untreated advanced hepatocellular carcinoma (ID1248). Expected date of issue to be confirmed. NICE Technology appraisal. Sorafenib for the treatment of advanced hepatocellular carcinoma (TA189). May 2010. NICE MedTech innovation briefing. SIR-Spheres for treating inoperable hepatocellular carcinoma (MIB63). March 2016. NICE MedTech innovation briefing. TheraSphere for treating operable and inoperable hepatocellular carcinoma (MIB62). March 2016. NICE Interventional procedures guidance. Chemosaturation via percutaneous hepatic artery perfusion and hepatic vein isolation for primary and metastatic liver cancer (IPG488). May 2014. NICE Interventional procedures guidance. Selective internal radiation therapy for primary hepatocellular carcinoma (IPG460). July 2013 NICE Interventional procedures guidance. Irreversible electroporation for treating primary liver cancer (IPG444). February 2013. NICE Interventional procedures guidance. Ex-vivo hepatic resection and reimplantation for liver cancer (IPG298). April 2009. NICE Interventional procedures guidance. Microwave ablation of hepatocellular carcinoma (IPG214). March 2007. NICE Interventional procedures guidance. Laparoscopic liver resection (IPG135). July 2005. NICE Interventional procedures guidance. Radiofrequency ablation of hepatocellular carcinoma (IPG2). July 2003. NICE quality standard. Liver disease (QS152). June 2017. NHS ENGLAND and POLICY
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