Data support progressing with Phase 3 clinical development program
Lexington, Mass. – October 27, 2016 –– For U.S. Audiences Only – Shire plc (LSE: SHP, NASDAQ: SHPG) today presented data from a Phase 2 study evaluating maribavir (SHP620), an investigational antiviral 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 currently used to treat these infections. In the study, 67% of patients treated with varying doses of maribavir (400 to 1200 mg twice daily) for up to 24 weeks had no detectable levels of the virus in their blood plasma within six weeks of starting treatment. Dysgeusia (taste disturbance) was the most commonly-reported treatment-emergent adverse event (AE) in this study. Other treatment-emergent AEs ≥20% for all doses included nausea, vomiting, CMV infection, diarrhea, fatigue, and anemia.
These data were presented during an oral abstract session at Infectious Disease Week (IDWeek) 2016 in New Orleans, La.
"Cytomegalovirus infection that is resistant or refractory to standard therapy in transplant patients is associated with significant complications and high mortality," said Genovefa Papanicolaou, M.D., Infectious Diseases Specialist at Memorial Sloan Kettering Cancer Center, and one of the clinical trial investigators. “The Phase 2 findings support further research to confirm these results among patients who have limited options to combat the infection.”
Cytomegalovirus (CMV) is a common infection that is related to the 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. While currently-available systemic anti-CMV agents are effective against the virus, their use is limited by complications, most notably bone marrow suppression which can be problematic in patients who have undergone a hematopoietic stem cell transplant, and impairment of kidney function. Emergence of resistance against commonly used drugs can also be a problem for this population and there is a need for treatments to treat CMV infection that does not respond or is resistant to these drugs.
Maribavir has shown activity against CMV strains resistant to other agents. The agent was originally being developed by ViroPharma, Incorporated, which Shire acquired in November 2013. The U.S. Food and Drug Administration (FDA) and the European Commission have granted Orphan Drug Designation to maribavir for treatment of clinically significant cytomegalovirus viremia and disease in at-risk patients, and treatment of cytomegalovirus disease in patients with impaired cell mediated immunity, respectively.
Howard B. Mayer, M.D. Head of Global Clinical Development, Shire, 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 study included 120 patients ages 12 or older with CMV infection (≥1,000 DNA copies/mL of blood plasma) resistant or refractory to (val)ganciclovir or foscarnet. Patients were randomized to one of three, twice-daily oral doses of maribavir – 400 mg, 800 mg, or 1,200 mg – for up to 24 weeks of treatment. The primary safety analysis focused on the incidence of treatment-emergent AEs. The primary efficacy endpoint was the proportion of patients with confirmed undetectable plasma CMV DNA within six weeks of treatment.
Overall, 67% (80/120) of patients met the primary efficacy endpoint (95% CI: 57, 75). The results by dosage were: 70% for 400 mg twice daily (95% CI: 53, 83), 63% for 800 mg twice daily (95% CI: 46, 77), and 67% for 1,200 mg twice daily (95% CI: 51, 81). The infection recurred in 30 patients, including 7, 11, and 12 patients in the 400 mg, 800 mg, and 1,200 mg groups, respectively.
Dysgeusia was the most common AE, occurring in 65% of all patients, including 60%, 63%, and 73% of patients in the 400 mg, 800 mg, and 1,200 mg groups, respectively. Other treatment-emergent AEs ≥20% for all doses included nausea, vomiting, CMV infection, diarrhea, fatigue, and anemia. Immunosuppressant drug level increases were reported as an AE in 10% of patients. In the study, approximately 27% of patients died due to any AE, one of which (multi-organ failure) was considered by the investigator to be possibly related to study drug.
For more information, visit https://clinicaltrials.gov/ct2/show/NCT01611974.
Shire is planning to initiate two large randomized Phase 3 studies of maribavir for the treatment of CMV infection in transplant patients later this year. The first study SHP620-303 is a randomized study comparing maribavir to investigator’s choice anti-CMV treatment among transplant patients with resistant and/or refractory CMV disease.
The second study is a randomized double blind study SHP620-302 which will compare maribavir to oral valganciclovir among patients with hematopoietic stem cell transplant and asymptomatic CMV infection.
Maribavir, a member of a class of drugs called benzimidazole ribosides, is an orally bioavailable antiviral compound being investigated in patients with cytomegalovirus infection undergoing hematopoietic stem cell transplant or solid organ transplant who are resistant or refractory to drugs currently used to treat these infections. Maribavir is thought to inhibit viral DNA assembly and egress of viral capsids from the nucleus of infected cells. It has not been shown to affect the maturation of viral DNA or affect the viral DNA polymerase.
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