New Medicines

Pexa-VecAdvanced hepatocellular carcinoma (HCC)



Development and Regulatory status

Dec 21HCC not listed in company pipeline; assume development discontinued [16].
Nov 15Transgene remains responsible for submitting regulatory approvals and commercialisation activities in the EU [10].
Nov 15 Transgene and SillaJen amend a development and commercialisation agreement signed in September 2010 for pexastimogene devacirepvec. Under the terms of amended agreement, SillaJen will be responsible for conducting the PIII PHOCUS trial in hepatocellular carcinoma [10].
Mar 15Phase 2 trials ongoing [9].


Genetically-engineered strain of oncolytic vaccinia virus
Hepatocellular carcinoma affects approximately 1 in 10,000 people in the EU; equivalent to approximately 51,000 people.
Advanced hepatocellular carcinoma (HCC)

Trial or other data

Aug 19PIII PHOCUS study has been stopped early as it is unlikely to meet its primary outcome [15].
Dec 18PIII PHOCUS (NCT02562755) study is still recruiting. Collection of primary outcome data should now complete Jul 19 [14].
Dec 17PIII PHOCUS (NCT02562755) study is continuing recruitment. Collection of primary outcome data should now complete Oct 18 [13].
Dec 16PIII PHOCUS (NCT02562755) study is still recruiting; timescales unchanged [12].
Oct 15PIII PHOCUS (NCT02562755) study begins recruitment. Collection of primary outcome data should complete in Oct 17 [11].
Apr 15Transgene reached an agreement with the US FDA upon a Special Protocol Assessment (SPA) for the pivotal PIII PHOCUS trial in the first line treatment of advanced HCC (JX594HEP024; NCT02562755). Earlier, in March 2015, Lees Pharmaceutical Holdings, SillaJen and Transgene jointly announced their plan to initiate the global trial in the fourth quarter of 2015. The primary objective of the randomised study is to determine the overall survival benefit for patients receiving first-line therapy with pexastimogene devacirepvec followed by sorafenib, compared with sorafenib alone in approximately 600 patients in Asia, Europe and North America [10].
Mar 15NCT01171651 apparently ongoing in sorafenib-naive patients with advanced hepatocellular carcinoma; primary outcome tumour response up to 48 weeks [9].
Sep 13TRAVERSE PIIb trial did not reach its primary survival endpoint [8]
Feb 13In a study published in Nature Medicine (Volume 19, Issue 2), Pexa-Vec (JX-594) showed a statistically significant dose-dependent overall survival benefit with 14.1 months median overall survival for the high-dose group compared to 6.7 months for the low-dose group (p-value = 0.02) [7]
Sep 12Data from a PII study presented at the International Liver Cancer Association Meeting. 25 Asian patients with advanced HCC, 20 of whom were refractory to sorafenib, were treated with an initial IV dose of JX-594, and the majority of patients then received sequential intra-tumuoral doses of JX-594 at week one and three. The majority of patients subsequently received treatment with sorafenib. Safety was the primary objective. The sequential treatment regimen was well tolerated with transient flu-like symptoms and transient leukopenia being the most common side effects related to JX-594. Secondary endpoints included disease control and tumor response. Following treatment with JX-594 alone at 4 weeks, 62% of patients had disease control as measured by modified RECIST. Tumour biopsies of 4 patients showed all had local infection of JX-594 in tumour tissue while normal liver tissue was not affected, providing evidence of JX-594´s tumour selectivity and the ability to administer JX-594 IV. After 6 or 12 weeks, 59% of patients had disease control as measured by modified RECIST and 75% had objective responses by Choi criteria. Evidence of antitumor activity was observed in both sorafenib-naive and sorafenib-refractory patients. The company have treated more than 160 patients with JX-594 to date and are actively enrolling a multinational PIIb study in second line treatment of HCC, a PII all-IV trial in first line HCC patients, and a PII study in colorectal cancer [6].
Sep 11Jennerex will start TRAVERSE, a global, randomized, controlled PIIb trial of JX-594 in patients with hepatocellular carcinoma who have failed sorafenib treatment in 2012 [5].
Sep 11Interim data from a PII trial of JX-594 in patients with advanced liver cancer reported at the Fifth Annual International Liver Cancer Association Conference. The study has enrolled 15 patients to date, including a subgroup of 10 who have failed previous treatment with sorafenib. Patients were treated with a combination of IV and intratumoural injections of JX-594 prior to standard sorafenib therapy. Tumour responses by Choi criteria (a measure of tumor necrosis) in both injected and non-injected tumours were observed in 8 of 11 evaluable patients and were maintained for up to 15 months. Significant tumour necrosis following JX-594 and sorafenib was observed in 6 of 7 evaluable sorafenib resistant patients (86%). The sequential treatment regimen was well-tolerated [5].
Apr 11Data were from a study of 35 patients with hepatocellular carcinoma or liver metastases given intratumoural injections of JX-594 (up to 8 treatments) were presented at the annual EASL meeting. 23 patients (66%) had significant tumour necrosis and responses by modified Choi criteria (decreased tumour density). Choi responses were also documented in non-injected tumours. 7 patients exhibited objective response by RECIST criteria, including 2 complete responses upon long-term follow-up and 20 patients (57%) had stable disease [4].
Sep 10Interim data from a pilot trial of JX-594 followed by sorafenib in liver cancer were presented today at the Annual International Liver Cancer Association Conference, Canada. The trial has enrolled 9 patients so far including a number who have failed previous treatment with sorafenib; 7 patients have been evaluated for efficacy. All patients were treated with a combination of IV and intratumoural JX-594 followed by sorafenib. Six patients achieved Choi (necrotic) responses, 5 exhibited stable disease and one a partial response as defined by RECIST criteria. In all patients, the treatment regimen was well-tolerated. Safety is the primary endpoint of the trial [3].
Sep 10Transgene has entered into an agreement with Jennerex; the two companies will mount PII and PIII worldwide studies for JX-594, first for hepatocellular carcinoma (first and second line) and then colorectal cancer. Transgene has European and Middle East commercialization rights and sees JX-594 as a potential blockbuster in Europe with an approval schedule that could allow marketing in 2015 [2].
Apr 10Positive interim data from Phase II, randomised trial. Pts randomised to JX 594 at one of two dose levels given three times intratumorally at two-week intervals. Six month survival of pts treated at low dose (10% of full dose) and full dose was 48% and 75%, respectively and 12 month survival was 18% (low dose) and 75% (full dose). The full dose JX 594 group had superior survival when compared to historical controls including pts treated with sorafenib. After 8 wks, disease was controlled in 15 (88%) pts. 50% of evaluable pts achieved a Choi (necrotic) response on dynamic contrast-enhanced MRI scan. Treatment was typically associated with transient flu-like symptoms generally lasting less than 24 hours. No pts had treatment discontinued due to toxicities. (1)