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Committee for Medicinal Products for Human Use | CHMP Positive Opinion | June | Europe Drug Approvals | 2024 | iPharmaCenter

Lynparza and Imfinzi Combination Recommended for EU Approval by CHMP for Advanced or Recurrent Endometrial Cancer

AstraZeneca announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending the approval of Lynparza (olaparib) and Imfinzi (durvalumab) for the treatment of patients with advanced or recurrent endometrial cancer. The recommendation includes two regimens: Imfinzi plus chemotherapy followed by Lynparza and Imfinzi for patients with mismatch repair proficient (pMMR) disease, and Imfinzi plus chemotherapy followed by Imfinzi alone for those with mismatch repair deficient (dMMR) disease.

The CHMP's recommendation is grounded in data from the DUO-E Phase III trial. The trial included a prespecified exploratory subgroup analysis based on mismatch repair (MMR) status. The analysis revealed that for patients with pMMR disease, the combination of Lynparza and Imfinzi reduced the risk of disease progression or death by 43% (median progression-free survival [PFS] of 15.0 months vs. 9.7 months) compared to the control arm. For patients with dMMR disease, Imfinzi alone reduced the risk of disease progression or death by 58% (median PFS not reached vs. 7.0 months).

Endometrial cancer is the fourth most common cancer among women in Europe, with nearly 125,000 diagnoses and over 30,000 deaths in 2022. Early-stage diagnosis offers a five-year survival rate of about 80-90%, but this rate plummets to less than 20% for advanced disease. There is a substantial need for new treatment options, particularly for the 70-80% of patients with pMMR disease. This recommendation emphasizes the importance of MMR testing at diagnosis, which is already well established and accessible.

The safety profiles of the recommended regimens were manageable and consistent with the known profiles of the individual drugs.

Regulatory reviews for Imfinzi and Lynparza based on the DUO-E trial are ongoing in Japan and several other countries. In the US, Imfinzi plus chemotherapy has recently been approved for dMMR patients with primary advanced or recurrent endometrial cancer.

DUO-E Trial Details

The DUO-E trial (GOG 3041/ENGOT-EN10) is a large, randomized, double-blind, placebo-controlled, multicenter Phase III study investigating the efficacy of 1st-line Imfinzi plus platinum-based chemotherapy (carboplatin and paclitaxel), followed by either Imfinzi alone or Imfinzi plus Lynparza as maintenance therapy, compared to chemotherapy alone in newly diagnosed advanced or recurrent endometrial cancer patients.

In the trial, 699 patients were randomized to receive either Imfinzi (1120 mg) or placebo every three weeks, in addition to standard platinum-based chemotherapy. Post-chemotherapy, patients without disease progression received either Imfinzi (1500 mg) or placebo every four weeks as maintenance, along with Lynparza (300 mg BID) or placebo until disease progression.

The primary endpoint of the study was progression-free survival (PFS) for each treatment arm compared to the standard of care. Secondary endpoints included overall survival (OS), safety, and tolerability. The trial continues to assess OS for both Imfinzi monotherapy and Imfinzi plus Lynparza in the overall population.


Merck Gains Favorable EU CHMP Opinion for Winrevair in Treating Pulmonary Arterial Hypertension (PAH)

If the European Commission approves, Winrevair (sotatercept) will become the first activin signaling inhibitor therapy for PAH available in Europe, providing a new therapeutic option for certain adults with this rare and progressive condition.

This milestone underscores Merck's dedication to broadening the accessibility of Winrevair globally and its commitment to supporting PAH patients.

Merck announced today that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has endorsed the approval of Winrevair (sotatercept) for use alongside other PAH treatments. This recommendation applies to adult patients with Pulmonary Arterial Hypertension (PAH) classified as WHO Functional Class II to III, aiming to enhance exercise capacity. Winrevair had previously received the EMA's Priority Medicines (PRIME) and orphan drug designations for PAH treatment.

Administered as a single injection under the skin every three weeks, WINREVAIR can be given by patients or caregivers with proper training, guidance, and follow-up from healthcare professionals.

The CHMP's positive opinion is based on results from the Phase 3 STELLAR trial, which evaluated WINREVAIR in combination with existing PAH therapies against the therapies alone. The study revealed that Winrevair significantly improved the primary endpoint, a 6-minute walk distance, and several key secondary outcomes, including reducing the risk of death from any cause or PAH-related clinical deterioration.

The STELLAR trial (NCT04576988) was a global, double-blind, placebo-controlled, multicenter study. It involved 323 PAH patients (WHO Group 1, Functional Class II or III), who were randomly assigned to receive either Winrevair (target dose 0.7 mg/kg) (n=163) or a placebo (n=160) every three weeks in addition to stable background therapy.

The most common causes of PAH among participants were idiopathic PAH (59%), heritable PAH (18%), and PAH related to connective tissue diseases (15%). A majority of the patients were on either three (61%) or two (35%) background medications for PAH, with 40% receiving prostacyclin infusions. The average duration since PAH diagnosis was 8.8 years, and patients were classified as WHO Functional Class II (49%) or III (51%) at the study's start.


Roche's Vabysmo Receives CHMP Recommendation for Retinal Vein Occlusion Treatment

Roche has announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive recommendation for extending the marketing authorization of Vabysmo (faricimab) to include the treatment of visual impairment due to macular edema secondary to retinal vein occlusion (RVO).

This endorsement is based on data from two Phase III clinical trials, BALATON and COMINO, which involved over 1,200 participants with macular edema resulting from branch and central retinal vein occlusion (BRVO and CRVO). The studies demonstrated that Vabysmo provided early and sustained vision improvements that were comparable to those achieved with aflibercept, along with significant retinal drying. Vabysmo was well tolerated, and its safety profile was consistent with previous research.

Currently, Vabysmo is the first and only bispecific antibody treatment approved in the US and Japan for RVO and is available in more than 95 countries for treating neovascular or ‘wet’ age-related macular degeneration (nAMD) and diabetic macular edema (DME). If the European Commission approves this extension, Vabysmo will be the first treatment of its kind available for people with RVO in the European Union.

The Phase III studies, BALATON (NCT04740905) and COMINO (NCT04740931), were randomized, multicenter, global trials comparing the efficacy and safety of Vabysmo (faricimab) to aflibercept. During the initial 20 weeks, patients received six monthly injections of either Vabysmo (6.0 mg) or aflibercept (2.0 mg). From weeks 24 to 72, all patients were treated with Vabysmo (6.0 mg) using a treat-and-extend dosing schedule, which could extend up to every four months.

The BALATON study included 553 participants with branch retinal vein occlusion, while the COMINO study involved 729 participants with central or hemiretinal vein occlusion. The primary measure of success in these studies was the change in best-corrected visual acuity from the baseline at 24 weeks. Secondary measures included changes in central subfield thickness and retinal fluid drying from baseline through week 24.

Roche stated that it remains dedicated to advancing treatments to prevent vision loss.


AbbVie Gains Positive CHMP Opinion for Tepkinly for Adults with Relapsed/Refractory Follicular Lymphoma

AbbVie announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a favorable opinion recommending conditional marketing authorization for Tepkinly (epcoritamab). This T-cell engaging bispecific antibody, administered subcutaneously, would be the first and only monotherapy approved in the European Union for treating adults with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more prior therapies.

The European Commission is expected to make a decision on this indication for epcoritamab later this year. If approved, epcoritamab will also be the first bispecific antibody conditionally approved for both relapsed or refractory FL and diffuse large B-cell lymphoma (DLBCL) after multiple lines of treatment.

Follicular lymphoma is a slow-growing type of non-Hodgkin's lymphoma (NHL) originating from B-lymphocytes, and it represents 20-30% of all NHL cases. In 2023, around 13,000 FL cases were estimated in Western Europe. Current standard treatments do not cure FL.

The CHMP's recommendation is based on the Phase 1/2 EPCORE® NHL-1 study, which included 128 patients with R/R FL who had undergone at least two previous therapies. This study included patients who were resistant to both anti-CD20 monoclonal antibody therapy and an alkylating agent, those refractory to their most recent treatment, and those whose disease progressed within two years of initial systemic therapy. The safety profile of epcoritamab was consistent with previous reports from the pivotal EPCORE NHL-1 DLBCL cohort.

An additional cohort of 86 patients tested a 3-step-up dosing schedule designed to lessen the severity of cytokine release syndrome (CRS), a known adverse effect of immune-engaging cancer treatments. For the first full dose in this regimen, hospitalization was not mandatory. In this group, 49% (42 out of 86) experienced CRS, with 9% experiencing grade 2 CRS. No grade 3 or higher CRS events were reported.

EPCORE NHL-1 is an open-label, multi-center study assessing the safety and preliminary efficacy of subcutaneous epcoritamab in patients with relapsed, progressive, or refractory CD20+ mature B-cell non-Hodgkin's lymphoma (B-NHL), including FL. The trial has three parts: dose escalation, expansion, and optimization. The expansion phase enrolled additional patients to further examine the safety and efficacy of epcoritamab in three cohorts with different types of relapsed/refractory B-NHLs who have limited treatment options. The optimization phase explores alternative dosing regimens to minimize Grade 2 CRS and prevent Grade 3 or higher CRS.

The primary endpoint for the expansion part was the overall response rate (ORR) as assessed by an independent review committee (IRC). Secondary endpoints included duration of response, complete response rate, duration of complete response, progression-free survival, and time to response. The optimization part's primary endpoint was the rate of Grade 2 or higher CRS events and all-grade CRS events from the first dose through seven days after the second full dose.

Epcoritamab is an investigational IgG1-bispecific antibody developed using Genmab's proprietary DuoBody technology. This technology directs cytotoxic T cells to target specific cell types, aiming to enhance the immune response against these cells. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells, facilitating T-cell-mediated destruction of CD20+ cells.


Odronextamab Recommended for EU Approval by CHMP for Treating Relapsed/Refractory Follicular Lymphoma and Diffuse Large B-Cell Lymphoma

Regeneron announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has given a positive opinion recommending conditional marketing authorization for odronextamab. This recommendation supports using odronextamab to treat adults with relapsed or refractory (R/R) follicular lymphoma (FL) or R/R diffuse large B-cell lymphoma (DLBCL) after they have undergone two or more lines of systemic therapy.

FL and DLBCL are the most prevalent subtypes of B-cell non-Hodgkin lymphoma (B-NHL). FL, a slow-progressing form, is incurable, with most patients experiencing a relapse post-treatment. DLBCL is a more aggressive form, with up to 50% of high-risk patients seeing disease progression after initial therapy, including cases that are refractory to treatment. Annually, about 120,000 cases of FL and 163,000 cases of DLBCL are diagnosed globally. In Europe, the estimated yearly diagnoses are 15,000 for FL and 31,000 for DLBCL.

The positive CHMP opinion is based on data from the Phase 1 ELM-1 and the pivotal Phase 2 ELM-2 trials. These studies showed that odronextamab produced robust and durable response rates with a safety profile that was acceptable in adults with R/R FL or R/R DLBCL. Among the most common serious adverse reactions reported in the pooled safety population were cytokine release syndrome, pneumonia, COVID-19, and fever.

Previously, the EMA granted odronextamab Orphan Designation for both FL and DLBCL. While odronextamab is still under clinical development and has not yet received approval from any regulatory authority, the ongoing research looks promising.

Regeneron is committed to further exploring the potential of odronextamab, both as a monotherapy and in combination with other treatments across earlier lines of therapy for difficult-to-treat lymphomas. This includes the registrational ELM-1 and ELM-2 studies, the Phase 3 OLYMPIA development program (one of the largest lymphoma clinical programs assessing odronextamab in earlier lines of therapy and other B-NHLs), and early-stage trials focusing on chemotherapy-free combination treatments.


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