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The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended refusal of marketing authorization for plitidepsin (Aplidin).
PharmaMar is seeking approval for plitidepsin to treat adults with multiple myeloma (MM) who have received at least 3 prior treatments, including bortezomib and either lenalidomide or thalidomide.
Plitidepsin is intended to be used in combination with dexamethasone.
This is the second time the CHMP has recommended against authorizing plitidepsin for this indication. The first time was last December.
At that time, PharmaMar asked the CHMP to re-examine its opinion, and the CHMP obliged. The committee confirmed its negative opinion of plitidepsin last week.
The CHMP’s review
Upon its initial review, the CHMP was concerned that data from the main study of plitidepsin in MM—the phase 3 ADMYRE trial—did not demonstrate a sufficient benefit of plitidepsin plus dexamethasone, compared to dexamethasone alone, in MM patients who had received 3 to 6 prior therapies.
The CHMP noted that the data showed a modest increase in progression free-survival (PFS)—around 1 month—with plitidepsin. According to study investigators, the median PFS was 3.8 months in patients who received plitidepsin and 1.9 months in those who received dexamethasone alone. According to an independent review committee, the median PFS was 2.6 months and 1.7 months, respectively.
The CHMP also said improvement in overall survival (OS) was not sufficiently demonstrated in this trial. The median OS was 11.6 months in the plitidepsin arm and 6.4 months in the dexamethasone arm.
Finally, the CHMP noted that severe adverse events were reported more frequently in patients who received plitidepsin. The most common grade 3/4 treatment-related adverse events (in the plitidepsin and dexamethasone arms, respectively) were fatigue (10.8% vs 1.2%), myalgia (5.4% vs 0%), and nausea (3.6% vs 1.2%).
Rates of treatment discontinuation were 9% in the plitidepsin arm, 6.5% in the dexamethasone arm, and 13.5% among patients who crossed over from the dexamethasone arm to the plitidepsin arm. Patients were allowed to cross over if they progressed after at least 8 weeks of treatment.
Based on these data, the CHMP was of the opinion that the benefits of plitidepsin did not outweigh its risks, so the committee recommended refusal of marketing authorization. After re-examination, the CHMP remained of the same opinion.
The European Commission (EC) has the final say on the marketing authorization application for plitidepsin. Though it is not required to do so, the EC typically follows the CHMP’s advice. The EC makes its decision within 67 days of the CHMP’s opinion.
PharmaMar has not announced whether it plans to continue developing plitidepsin for MM patients if the EC refuses to authorize the drug, and the company did not respond to a request for comment.
About plitidepsin
Plitidepsin is an investigational anticancer agent of marine origin, originally obtained from the ascidian Aplidium albicans. The drug specifically binds to eEF1A2 and targets the non-canonical role of this protein, resulting in cancer cell death via apoptosis.
Plitidepsin is currently in clinical development for hematologic malignancies.
In a phase 1b trial (NCT02100657), researchers are evaluating plitidepsin in combination with bortezomib and dexamethasone for patients with relapsed/refractory MM.
In a phase 2 trial (NCT03117361), researchers are investigating plitidepsin in combination with bortezomib and dexamethasone for patients with MM that is refractory to both lenalidomide and bortezomib.
Plitidepsin has received orphan drug designation in the European Union and the US.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended refusal of marketing authorization for plitidepsin (Aplidin).
PharmaMar is seeking approval for plitidepsin to treat adults with multiple myeloma (MM) who have received at least 3 prior treatments, including bortezomib and either lenalidomide or thalidomide.
Plitidepsin is intended to be used in combination with dexamethasone.
This is the second time the CHMP has recommended against authorizing plitidepsin for this indication. The first time was last December.
At that time, PharmaMar asked the CHMP to re-examine its opinion, and the CHMP obliged. The committee confirmed its negative opinion of plitidepsin last week.
The CHMP’s review
Upon its initial review, the CHMP was concerned that data from the main study of plitidepsin in MM—the phase 3 ADMYRE trial—did not demonstrate a sufficient benefit of plitidepsin plus dexamethasone, compared to dexamethasone alone, in MM patients who had received 3 to 6 prior therapies.
The CHMP noted that the data showed a modest increase in progression free-survival (PFS)—around 1 month—with plitidepsin. According to study investigators, the median PFS was 3.8 months in patients who received plitidepsin and 1.9 months in those who received dexamethasone alone. According to an independent review committee, the median PFS was 2.6 months and 1.7 months, respectively.
The CHMP also said improvement in overall survival (OS) was not sufficiently demonstrated in this trial. The median OS was 11.6 months in the plitidepsin arm and 6.4 months in the dexamethasone arm.
Finally, the CHMP noted that severe adverse events were reported more frequently in patients who received plitidepsin. The most common grade 3/4 treatment-related adverse events (in the plitidepsin and dexamethasone arms, respectively) were fatigue (10.8% vs 1.2%), myalgia (5.4% vs 0%), and nausea (3.6% vs 1.2%).
Rates of treatment discontinuation were 9% in the plitidepsin arm, 6.5% in the dexamethasone arm, and 13.5% among patients who crossed over from the dexamethasone arm to the plitidepsin arm. Patients were allowed to cross over if they progressed after at least 8 weeks of treatment.
Based on these data, the CHMP was of the opinion that the benefits of plitidepsin did not outweigh its risks, so the committee recommended refusal of marketing authorization. After re-examination, the CHMP remained of the same opinion.
The European Commission (EC) has the final say on the marketing authorization application for plitidepsin. Though it is not required to do so, the EC typically follows the CHMP’s advice. The EC makes its decision within 67 days of the CHMP’s opinion.
PharmaMar has not announced whether it plans to continue developing plitidepsin for MM patients if the EC refuses to authorize the drug, and the company did not respond to a request for comment.
About plitidepsin
Plitidepsin is an investigational anticancer agent of marine origin, originally obtained from the ascidian Aplidium albicans. The drug specifically binds to eEF1A2 and targets the non-canonical role of this protein, resulting in cancer cell death via apoptosis.
Plitidepsin is currently in clinical development for hematologic malignancies.
In a phase 1b trial (NCT02100657), researchers are evaluating plitidepsin in combination with bortezomib and dexamethasone for patients with relapsed/refractory MM.
In a phase 2 trial (NCT03117361), researchers are investigating plitidepsin in combination with bortezomib and dexamethasone for patients with MM that is refractory to both lenalidomide and bortezomib.
Plitidepsin has received orphan drug designation in the European Union and the US.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended refusal of marketing authorization for plitidepsin (Aplidin).
PharmaMar is seeking approval for plitidepsin to treat adults with multiple myeloma (MM) who have received at least 3 prior treatments, including bortezomib and either lenalidomide or thalidomide.
Plitidepsin is intended to be used in combination with dexamethasone.
This is the second time the CHMP has recommended against authorizing plitidepsin for this indication. The first time was last December.
At that time, PharmaMar asked the CHMP to re-examine its opinion, and the CHMP obliged. The committee confirmed its negative opinion of plitidepsin last week.
The CHMP’s review
Upon its initial review, the CHMP was concerned that data from the main study of plitidepsin in MM—the phase 3 ADMYRE trial—did not demonstrate a sufficient benefit of plitidepsin plus dexamethasone, compared to dexamethasone alone, in MM patients who had received 3 to 6 prior therapies.
The CHMP noted that the data showed a modest increase in progression free-survival (PFS)—around 1 month—with plitidepsin. According to study investigators, the median PFS was 3.8 months in patients who received plitidepsin and 1.9 months in those who received dexamethasone alone. According to an independent review committee, the median PFS was 2.6 months and 1.7 months, respectively.
The CHMP also said improvement in overall survival (OS) was not sufficiently demonstrated in this trial. The median OS was 11.6 months in the plitidepsin arm and 6.4 months in the dexamethasone arm.
Finally, the CHMP noted that severe adverse events were reported more frequently in patients who received plitidepsin. The most common grade 3/4 treatment-related adverse events (in the plitidepsin and dexamethasone arms, respectively) were fatigue (10.8% vs 1.2%), myalgia (5.4% vs 0%), and nausea (3.6% vs 1.2%).
Rates of treatment discontinuation were 9% in the plitidepsin arm, 6.5% in the dexamethasone arm, and 13.5% among patients who crossed over from the dexamethasone arm to the plitidepsin arm. Patients were allowed to cross over if they progressed after at least 8 weeks of treatment.
Based on these data, the CHMP was of the opinion that the benefits of plitidepsin did not outweigh its risks, so the committee recommended refusal of marketing authorization. After re-examination, the CHMP remained of the same opinion.
The European Commission (EC) has the final say on the marketing authorization application for plitidepsin. Though it is not required to do so, the EC typically follows the CHMP’s advice. The EC makes its decision within 67 days of the CHMP’s opinion.
PharmaMar has not announced whether it plans to continue developing plitidepsin for MM patients if the EC refuses to authorize the drug, and the company did not respond to a request for comment.
About plitidepsin
Plitidepsin is an investigational anticancer agent of marine origin, originally obtained from the ascidian Aplidium albicans. The drug specifically binds to eEF1A2 and targets the non-canonical role of this protein, resulting in cancer cell death via apoptosis.
Plitidepsin is currently in clinical development for hematologic malignancies.
In a phase 1b trial (NCT02100657), researchers are evaluating plitidepsin in combination with bortezomib and dexamethasone for patients with relapsed/refractory MM.
In a phase 2 trial (NCT03117361), researchers are investigating plitidepsin in combination with bortezomib and dexamethasone for patients with MM that is refractory to both lenalidomide and bortezomib.
Plitidepsin has received orphan drug designation in the European Union and the US.