Pre-registration Rigvir® clinical study summary

Clinical studies of Rigvir® began in 1968 in Riga, Latvia. More than 700 patients who had been diagnosed with late-stage melanoma, stomach and gastrointestinal tract cancer were involved in the pre-registration safety and efficacy studies [1-5].

Approximately 190 late-stage melanoma, stomach and gastrointestinal tract cancers were involved in the Rigvir® safety studies [6-9]. The most commonly observed side effects were subfebrile temperatures, pain in the tumour area, fatigue, sleepiness and dyspepsia; all were reversible and lasted for only a few days. There was no intolerance or treatment-related discontinuation of the treatment.

More than 540 melanoma patients were involved in the Rigvir® efficacy studies. These studies showed that overall survival was prolonged for patients who had been treated with Rigvir® compared with those who had been treated only with surgery *. The main Rigvir® clinical studies showed increased 3-year survival in melanoma patients [1, 10-18]. The 3-year survival for patients who had been treated only with surgery was 46-58%, while patients who had also been treated with Rigvir® had a 3-year survival rate of 57-84% and a 5-year survival rate of 44-66%. The 3- and 5-year survival rates for eye melanoma patients were 90% and 70%, respectively.

The safety studies also yielded survival data in the approximately 160 participating stomach and gastrointestinal tract cancer patients. Thus, for Stage III stomach cancer patients the 5-year survival post-surgery rate was 24-33%, compared with 47-60% for those who had also been treated with Rigvir®. Furthermore, for Stage II-IV rectum cancer patients the 5-year post-surgery survival rate was 41-68%, compared with 71-78% for those who had also been treated with Rigvir® [1, 5, 19, 20].

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

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.
  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.
  4. Alberts, P., L. Brokāne, G. Proboka, D. Venskus, I. Jaunalksne, D. Reihmane, A. Tilgase, V. Telle, L. Patetko, A. Ramata Stunda, and M. Borodušķis, Virotherapy as an independent therapy in oncology: The Latvian model. (In Latvian: Viroterapija kā patstāvīga terapija onkoloğijā: Latvijas modelis.). Latvijas Ārsts, 2016. 5: p. 60-63.
  5. Brūvere, R., O. Heisele, A. Ferdats, A. Rupais, and A. Muceniece, Echovirus-mediated biotherapy for malignant tumours: 40 years of investigation. Third Baltic Congress of Oncology, 2-4 May, Vilnius, Lithuania, 2002(Abstract 216): p. 251.
  6. Konopatskova, O.M., A.N. Tahtamish, and I.N. Pavlova, Results of the use of the immunomodulator Rigvir in skin melanoma patients (In Russian). National scientific conference on Cancer Biotherapy, Moscow, 18-20 June, 2002.
  7. Priedīte, I., R. Garklava, R. Bruvere, L. Vitolina, and A. Muceniece, Results from treatment of rectal cancer (In Russian). III Conference of Estonian, Lithuanian and Latvian oncologists, Riga, 1971: p. 325.
  8. Januskevics, V.J., B. Popena, and I. Priedite, Postoperative immunostimulation of patients with colorectal cancer., in Modulation of postoperative anti-tumor immunity (In Russian). 1988, Zinatne: Riga. p. 95-101.
  9. Kunicina, T.A., J.J. Dmitrievs, and S.L. Tihova, Monitoring of the immunity of skin melanoma patients during the treatment with an enterovirus (In Russian). Symposium “The symptoms and treatment of skin melanomas.” Saratov, 13-14 Sept., 1990.
  10. Heisele, O., The effect of a viral immunomodulator on the immune reactivity of patients with skin malignant melanoma (In Russian) Thesis. 1987: p. 1-166.
  11. Rudzītis, M., R. Garklāva, B. Popēna, and I. Desjatnikova, Increased five-year survival of skin melanoma patients undergoing surgical treatment followed by immunomodulator treatment (In Russian). All-Union Symposium “Current issues of immunotherapy of tumours”, Jūrmala, Latvia 19-21 April, 1988. 2:pp. 19-20.
  12. Grigalinovičs, H., M. Rudzītis, M. Skudra, B. Popēna, I. Desjatnikova, and R. Garklāva, Effect of a viral immunomodulator (Rigvir®) on the morphology and survival of cutaneous melanoma patients (In Russian). Proceedings of the Latvian Academy of Sciences, 1988. 497(12): p. 72-75.
  13. 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.
  14. Ferdats, A., Viruses as immunomodulators of antitumour activity (In Russian). Thesis. 1989: p. 1-355.
  15. Muceniece, A., Rigvir – development of a viral immunomodulator and cancer virotherapy clinical trials (In Latvian). The 4th Latvian Congress of Physicians, Riga, 2001: p. 126-127.
  16. Čēma, I., G. Proboka, J. Tārs, A. Skağers, E. Kornevs, A. Muceniece, A. Bīgestāns, and G. Lauskis, Melanoma of the facial skin and oral mucosa (In Latvian). The 4th Latvian Congress of Physicians, 2001: p. 52.
  17. 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.
  18. Muceniece, A. and D. Venskus, How to assess immunity – the melanoma model. (In Latvian: Kā vērtēt imunitāti – melanomas modelis). 2007.
  19. Garklāva, R., I. Priedite, and A. Muceniece, Long-term results of surgical treatment of patients with gastric and rectal cancer after immunostimulation with a nonpathogenic enterovirus., in Immunocompetence and immunotherapy of cancer patients (In Russian). 1981: Kemerovo. p. 77-91.
  20. Muceniece, A., Cancer virotherapy. 1. Retrospection and justification (In Latvian: Ļaundabīgo audzēju viroterapija. 1. daļa – retrospekcija un pamatojums). Doctus, 2005. Nov.: p. 40-44.