Shire has reported positive data results from a Phase 2 study analysing maribavir (SHP620), an investigational anti-viral agent studied in patients with cytomegalovirus (CMV) infection undergoing hematopoietic stem cell transplant or solid organ transplant who are resistant or refractory to (val) ganciclovir or foscarnet, drugs that are used to treat these infections.
Memorial Sloan Kettering Cancer Centre infectious diseases specialist Genovefa Papanicolaou said: "Cytomegalovirus infection that is resistant or refractory to standard therapy in transplant patients is associated with significant complications and high mortality.
“The Phase 2 findings support further research to confirm these results among patients who have limited options to combat the infection.”
CMV is a common infection that is related to viruses that cause chickenpox and herpes simplex. The virus stays in the body for life once a person is infected, but may stay dormant.
It frequently occurs in patients undergoing transplant procedures whose immune system is compromised.
Maribavir has shown activity against CMV strains resistant to other agents. The agent was initally being developed by ViroPharma, which Shire acquired in November 2013.
The US Food and Drug Administration (FDA) and the European Commission have granted Orphan Drug Designation to maribavir for the treatment of clinically significant cytomegalovirus viremia and disease in at-risk patients, as well as treatment of cytomegalovirus disease in patients with impaired cell mediated immunity, respectively.
Shire global clinical development head Howard B Mayer said: “Shire has a strong commitment to continuing research for small and underserved patient populations.
"We are extremely encouraged by these Phase 2 results, and will be progressing forward with our Phase 3 research program to further evaluate this agent’s efficacy and safety in these patients.”
The Phase 2 trial included 120 patients with CMV infection resistant or refractory to (val)ganciclovir or foscarnet.
Patients were randomised to one of three, twice-daily oral doses of maribavir, 400mg, 800mg, or 1,200mg for up to 24 weeks of treatment.
The primary safety analysis focused on the incidence of treatment-emergent adverse events (AEs). The primary efficacy endpoint was the proportion of patients with confirmed undetectable plasma CMV DNA within six weeks of treatment.
Overall, 67% of patients met the primary efficacy endpoint. The results by dosage were: 70% for 400mg twice daily, 63% for 800mg twice daily and 67% for 1,200mg twice daily.
The infection recurred in 30 patients, including seven, 11, and 12 patients in the 400mg, 800mg, and 1,200mg groups, respectively.
Dysgeusia was the most common AE, occurring in 65% of all patients, including 60%, 63%, and 73% of patients in the 400mg, 800mg, and 1,200mg groups, respectively.
Other treatment-emergent AEs all doses included nausea, vomiting, CMV infection, diarrhea, fatigue, and anaemia.
Immunosuppressant drug level increases were reported as an AE in 10% of patients.
Approximately 27% of patients in the trial died due to any AE, one of which (multi-organ failure) was considered by the investigator to be potentially related to the study's drug.
Image: CMV infection of lung. Photo: courtesy of Dr Edwin P. Ewing, Jr / Wikipedia.