dm+d

Unassigned

New Medicines

Camvia Cytomegalovirus infections - treatment

Information

Camvia
New molecular entity
Takeda
Takeda

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Recommended for approval (Positive opinion)
Yes
Yes
Oct 21FDA advisory committee recommends use of maribavir for treatment of refractory CMV infection and disease with genotypic resistance to ganciclovir, valganciclovir, foscarnet or cidofovir in transplant recipients. The committee also voted unanimously to recommend use of maribavir for the treatment of refractory CMV infection and disease without genotypic resistance to ganciclovir, valganciclovir, foscarnet or cidofovir in transplant recipients [17].
Jul 21Filed in EU via centralised procedure [16].
May 21The FDA has accepted a New Drug Application for maribavir for the treatment of CMV infection in those that are refractory with or without resistance (R/R), in solid organ transplant (SOT) or hematopoietic cell transplant (HCT) recipients [15].
Jan 21Takeda still on track for filing/approval in 2021/2022. [12,13]
Feb 20Takeda anticipates approvals in financial year 2021/22 [10].
Nov 19Maribavir on quarterly report with target approval date of 2021.[9]
Jan 18Maribavir receives Breakthrough Therapy status for Cytomegalovirus infections in USA.[7]
Jan 17Estimated primary completion date of NCT02931539 is May 19 [5].
Dec 16Shire have initiated a PIII trial to assess the safety and efficacy of maribavir in transplant recipients with CMV infections that are refractory or resistant to treatment with ganciclovir, valganciclovir, foscarnet or cidofovir (SHP620-303; EudraCT2015-004725-13; NCT02931539). The randomised, open-label, active-controlled trial will enrol 351 patients, aged 12 years and older. Recruitment is underway in the US and is expected to extend to Belgium, Poland, Czech Republic, France, Netherlands, Italy, Spain, Germany, Sweden, Austria and the UK [4].
Jan 16Still listed as PII in Shire pipeline [3].
Mar 15NCT01611974 ongoing, but not recruiting participants. Primary completion date estimated as Sep 14, results awaited [2].
Jun 13Granted orphan drug status in the EU for treating cytomegaloviral (CMV) disease in patients with impaired cell mediated immunity. It has orphan drug status in the US for treatment of clinically significant CMV viraemia and disease in at-risk patients [1].

Category

Benzimidazole riboside that inhibits viral DNA assembly and inhibits egress of viral capsids from the nucleus of infected cells
Cytomegalovirus disease in patients with impaired cell-mediated immunity affects ~ 2 in 10,000 people in the EU, equivalent to a total of around 102,000 people
Cytomegalovirus infections - treatment
Oral

Further information

Yes

Trial or other data

Feb 21In a PIII study (n=352) of maribavir in transplant recipients with refractory CMV at eight weeks 55.7% of patients on maribavir (twice daily) had confirmed CMV viraemia clearance, compared to 23.9% of peers on standard of care (one or a combination of ganciclovir, vlaganciclovir, foscarnet or cidofovir). All patients had infections that were refractory to the most recently administered of four anti-CMV treatments. In addition to meeting its primary endpoing, Takeda also noted improvements in viral clearance and symptom control at week 16 with maribavir and lower rates of treatment-related toxicities such as neutropenia and AKI [14].
Dec 20PIII trial SOLSTICE (NCT02931539) a randomized, open-label, active-controlled trial compared eight weeks of treatment with either maribavir or investigator assigned treatment (IAT) in transplant recipients with CMV infection. The trial met its primary endpoint, the proportion of patients who achieved confirmed CMV viremia clearance compared to IAT at the end of week 8 (results to be presented) [11]
Sep 19Maribavir beat Roche’s valganciclovir (VGC) at clearing CMV from patients’ blood in a PII open-label study which compared the drugs in patients with CMV infection after receiving an organ transplant or a stem cell transplant. Three doses of maribavir in 159 adults were compared to VGC. After three weeks of treatment, 62% of maribavir patients had no signs of CMV in their blood plasma, compared to 56% of those on VGC. After six weeks, 79% of maribavir patients had cleared the virus, compared to 67% of VGC patients [8].
Mar 17PIII trial (SHP620-302; EudraCT2015-004726-34; NCT02927067) to assess the efficacy and safety of maribavir 200mg tablet vs. valganciclovir for treatment of CMV infection in asymptomatic haematopoietic stem cell transplant recipients. The randomised, double-blind, parallel, placebo-controlled trial will enrol approximately 550 pts globally including in the US and the UK and other European countries. The study is still recruiting and has a primary completion date of August 19. [6,7]
Dec 16PIII trial (SHP620-303; EudraCT2015-004725-13; NCT02931539) initiated to assess the safety and efficacy of maribavir in transplant recipients with CMV infections that are refractory or resistant to treatment with ganciclovir, valganciclovir, foscarnet or cidofovir. The randomised, open-label, active-controlled trial will enrol 351 pts, aged >12 years. Recruitment is underway in the US and Europe and the study has a primary completion date of May 19.[6,7]
Jun 13The previous focus of clinical development of maribavir was on the prevention of CMV disease in transplant patients. In PIII studies maribavir 100mg twice daily did not meet efficacy endpoints. Limited data from cases in which open-label maribavir has been used as CMV treatment suggest that higher doses may provide clinical activity and two PII dose ranging studies studies (400mg, 800mg or 1200mg twice daily) of maribavir in transplant recipients are ongoing. The first is a valganciclovir controlled multicentre study in up to 160 European hematopoietic stem cell or solid organ transplant recipients who have demonstrated CMV viraemia but do not have CMV organ disease. The second will enroll up to 120 haematopoietic stem cell or solid organ transplant recipients who have resistant or refractory CMV viraemia with or without CMV organ disease. This study is currently being conducted in the US with plans to extend to include European sites [1].

Evidence based evaluations

Camvia Cytomegalovirus (CMV) infections - first-line pre-emptive therapy post HSCT

Information

Camvia
Licence extension / variation
Takeda
Takeda

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Yes
Yes

Category

Benzimidazole riboside that inhibits viral DNA assembly and inhibits egress of viral capsids from the nucleus of infected cells
Cytomegalovirus (CMV) infection after HSCT is one of the fatal infectious complications related to host immune recovery. CMV reactivation rate, after HSCT, has been reported to be 30–70%, and may be associated with a higher non-relapse mortality rate [1].
Cytomegalovirus (CMV) infections - first-line pre-emptive therapy post HSCT
Oral