Date: 2014-10-28
Type of information: Results
phase: 2
Announcement: results
Company: Apogenix (Germany)
Product: APG101 (asunercept)
Action
mechanism: fusion protein. APG101 is a first-in-class, fully human fusion protein combining the extracellular domain of the CD95 receptor and the Fc portion of IgG. The interaction between the CD95 ligand and the CD95 receptor activates an intracellular signaling pathway that stimulates the invasive growth and migration of tumor cells, such as glioblastoma cells. APG101 binds to the CD95 ligand and thus inhibits activation of the CD95 signaling pathway, resulting in reduced tumor cell growth and migration. APG101 was granted orphan drug status for the treatment of glioma (EU/3/09/709) in the EU and for the treatment of glioblastoma and myelodysplastic syndromes in the US.
Disease: glioblastoma
Therapeutic area: Cancer - Oncology
Country: Austria, Germany, Russia
Trial
details: The phase II, open label, randomized clinical trial recruited 84 patients in 25 centers throughout Germany, Austria, and Russia. Glioblastoma patients were eligible for inclusion if they had suffered from a first or second relapse and if they no longer responded to treatment with temozolomide. Patients participated in this study until tumour progression. In December 2009, Apogenix started this controlled phase II trial with APG101 for the treatment of glioblastoma. The patient recruitment was completed in September 2011. The primary endpoint of the trial was successfully reached in March 2012. Apogenix was granted orphan drug designation for APG101 in 2009 for the treatment of glioblastoma in Europe and in the US.
Latest
news: * On July 26, 2012, Apogenix has announced that the phase II clinical proof of concept trial with APG101 as treatment of recurrent glioblastoma has met and exceeded expectations in the final analysis of the data.* On October 28, 2014, Apogenix, a clinical stage biopharmaceutical company, announced that the final data of the completed phase II clinical trial with APG101 in recurrent glioblastoma has been published in the peer-reviewed journal Clinical Cancer Research. The data demonstrates that treatment with APG101, a CD95 ligand-binding fusion protein, in combination with radiotherapy is an innovative concept that has shown clinical superiority in all study endpoints compared to treatment with radiotherapy alone. Both progression-free survival at six months, the primary endpoint of the trial, and median progression-free survival were met with statistical significance. In addition, an epigenetic biomarker was identified that indicates response to treatment with APG101. The trial showed a significant increase in median overall survival in biomarker-positive patients treated with APG101, as previously reported.* On January 13, 2014, Apogenix has announced the successful completion of its phase II proof-of-concept trial with APG101 in patients with recurrent glioblastoma. All endpoints of the randomized controlled trial that compared the efficacy and safety of a combination therapy of APG101 and radiotherapy versus radiotherapy alone were achieved or exceeded. During treatment with APG101 for up to two years, no drug-related serious adverse events were observed, underlining the excellent safety profile and very good tolerability of APG101. The study's primary endpoint - progression-free survival at six months (PFS6) - was met with a statistically significant fivefold improvement in the rate of patients reaching PFS6, as previously reported. The results demonstrate that patients having a newly-identified epigenetic biomarker associated with the CD95 ligand - the target of APG101 - experienced the greatest benefit from treatment with APG101. The trial showed a statistically significant (p=0.003) prolongation of overall survival in biomarker-positive patients treated with APG101, with a median overall survival of 16.1 months compared to 6.5 months in patients treated with radiotherapy alone. This biomarker will be validated in future clinical trials and in additional indications. A total of 84 patients at 25 clinical sites in Germany, Austria, and Russia participated in this randomized controlled phase II efficacy trial in recurrent glioblastoma. At this time, there are still seven surviving patients in the treatment group and one patient in the control group who are being monitored in order to collect overall survival data. Apogenix is currently developing a companion diagnostic to identify patients who will most likely respond best to treatment with APG101. Discussions are ongoing with the EMA and FDA to agree on a development strategy toward rapid approval of APG101 for the treatment of glioblastoma.The complete data set will be published in a high-impact medical journal.
In this randomized controlled clinical study the patients were treated either with a combination of APG101 plus radiotherapy (APG101+RT group) or radiotherapy alone (RT group). The primary objective of the trial was to increase the percentage of patients reaching progression free survival for six months (PFS6 - primary endpoint) by >100%. In addition, all the important secondary endpoints evaluated so far, including safety and tolerability, indicate that APG101 is a potent new treatment option for glioblastoma, with an excellent safety profile. The quality of life (QoL) as measured by a standardized questionnaire was maintained and even improved in 67% of the patients in the APG101+RT group, but worsened in 66% of patients in the RT group. In addition, in more than 50% of the APG101 treated patients medication with corticosteroids could be reduced or even stopped compared to only 28% of patients from the RT group. During treatment with APG101 for up to two years, no drug-related serious adverse events were observed.
APG101 Study Results
APG101+ RT Group: PFS6 20.7% - PFS (median) 19.7 weeks
RT Group: PFS6 3.8% - PFS (median) 10.8 weeks
Apogenix is currently planning a phase II proof of concept trial with APG101 in Myelodysplastic syndromes (MDS). The trial is expected to begin in the first half 2013.
