Virotherapy

Pre-registration Rigvir® clinical study summary

The Rigvir® clinical studies were started in 1968 in Riga, Latvia. More than 700 patients that had been diagnosed with late stage melanoma, stomach and gastrointstinal tract cancer were involved in the pre-registration safety and efficacy studies [1-3].

Approximately 190 late stage melanoma, stomach and gastrointestinal tract cancer were involved in the Rigvir® safety studies. The most commonly observed side effects were sub febrile temperature, pain in the tumour area, fatigue, sleepiness, and dyspepsia; all were reversible and lasted for a couple of days. There was no intolerance or treatment related discontinuation of treatment.

More than 540 melanoma patients were involved in the Rigvir® efficacy studies. These studies showed that the overall survival was prolonged for patients that had been treated with Rigvir® compared with those that had been treated with surgery only*. The main Rigvir® clinical studies showed increased 3-year survival in melanoma patients [4, 5]. The 3-year survival for patients that had been treated with surgery only was 46-58%, while patients that had also been treated with Rigvir® had a 3-year survival of 57-84% and a 5-year survival of 44-66%. The 3- and 5-year survival for eye melanoma patients were 90% un 70%, respectively.

The safety studies yielded also survival data in the participating approximately 160 stomach and gastrointestinal tract cancer patients. Thus, for stage III stomach cancer patients the 5-year survival post-surgery was 24-33%, compared with 47-60% for those that had also been treated with Rigvir®. Furthermore, for stage II-IV rectum cancer patients the 5-year survival post-surgery was 41-68%, compared with 71-78% for those that had also been treated with Rigvir® [1-3].

* Now 5-year survival data are required for registration, while for most drugs registered at the turn of the millennium (and are still widely used) such data were not available at the time of approval. Interestingly, the Rigvir® clinical studies conducted during the 1970ies and 1980ies recorded 3- and 5-year survival.

Post-registration experience

Oncolytic virus Rigvir® extends progression-free time in stage 2 melanoma patients in a retrospective study.

This retrospective study was published in the medical journal “Latvijas Ārsts” (Latvian physician).  The progression-free period post-surgery of stage II melanoma patients was analysed. The results show that patients treated with Rigvir® had 6.7 times lower risk of progression than those who, following current guidelines, had received no therapy and were only observed. For an English summary, please see [6].

Immunotherapy with oncolytic virus Rigvir® extends survival of melanoma patients after surgical removal of the tumour in a retrospective study.

The results of a retrospective study on oncolytic virotherapy efficiency have been published in the medical journal Melanoma Research [2].

The retrospective study compares the survival of stage IB-IIC melanoma patients treated with Rigvir® and patients who, following current guidelines, had received no therapy post-surgery and were only observed. The results show that the patients treated with Rigvir® had 4.39 to 6.57 times lower mortality, that is they were 4-6 times more likely to survive.

In addition, the publication suggests that Rigvir® has an excellent safety profile. Therefore, oncolytic virotherapy is a considerable gain for many patients.

Long-term treatment with oncolytic virus Rigvir®; 3 case reports.

The medical journal APMIS (Acta Pathologica, Microbiologica et Immunologica Scandinavia) [3] has published three case reports from Latvia whose time since diagnoses exceeds life expectancy. The patients had been diagnosed with histiocytic sarcoma stage 4, small-cell lung cancer stage 3, and melanoma stage 4. The patients have received virotherapy for several years and during the treatment their health condition and quality of life have considerably improved. The patients undergoing Rigvir® treatment were diagnosed 6.6, 3.5 and 7 years before publication (summer of 2016), respectively, and their condition improved and remained stable during the treatment. These results are promising and suggests that long-term virotherapy with Rigvir® is effective in treating melanoma as well as sarcoma and small-cell lung cancer.

References

  1. Brūvere, R., O. Heisele, A. Ferdats, A. Rupais, and A. Muceniece, Echovirus-mediated biotherapy for malignant tumours: 40 years of investigation. Acta medica Lituanica, 2002. Suppl. 9: p. 97-100.
  2. Doniņa, S., I. Strēle, G. Proboka, J. Auziņš, P. Alberts, B. Jonsson, D. Venskus, and A. Muceniece, Adapted ECHO-7 virus Rigvir immunotherapy (oncolytic virotherapy) prolongs survival in melanoma patients after surgical excision of the tumour in a retrospective study. Melanoma Research, 2015. 25(5): p. 421-426. http://journals.lww.com/melanomaresearch/Fulltext/2015/10000/Adapted_ECHO_7_virus_Rigvir_immunotherapy.7.aspx
  3. Alberts, P., E. Olmane, L. Brokāne, Z. Krastiņa, M. Romanovska, K. Kupčs, S. Isajevs, G. Proboka, R. Erdmanis, J. Nazarovs, and D. Venskus, Long-term treatment with the oncolytic ECHO-7 virus Rigvir of a melanoma stage IV M1c patient, a small cell lung cancer stage IIIA patient, and a histiocytic sarcoma stage IV patient-three case reports. APMIS, 2016. 124(10): p. 896-904. http://onlinelibrary.wiley.com/doi/10.1111/apm.12576/full
  4. Muceniece, A., M. Rudzītis, R. Brūvere, I. Desjatnikova, A. Ferdats, R. Garklāva, O. Heisele, B. Popēna, and A. Volrāte, A specially selected and adapted human enterovirus as a biological response modifier with antitumor activity in the treatment of human malignant skin melanoma. Second International Conference on Melanoma, Venice, Poster Sessions, 16-19 October., 1989: p. 316.
  5. Brūvere, R., G. Feldmane, A. Ferdats, O. Heisele, and A. Muceniece, Adjuvant immunotheraphy with virus-mediated biomodulators developed in Latvia: experimental and clinical data. Abstracts of the Perspectives in Melanoma X and The Third Annual International Melanoma Research Congress 14-16 September, Noordwijk, The Netherlands. Melanoma Research, 2006. 16(Suppl 1): p. S34-ABS-0058.
  6. Alberts, P., Rigvir. Safe and effective cancer therapy. Cancer Virotherapy, 2015. 1(1): p. 6-9. https://www.cancervirotherapy.eu/#