dm+d

Unassigned

New Medicines

Pepaxti (EU), Pepaxto (US) Relapsed or refractory multiple myeloma (MM) in adults - with dexamethasone after three prior regimens (inc. lenalidomide and a proteasome inhibitor)

Information

Pepaxti (EU), Pepaxto (US)
New molecular entity
Oncopeptides
Oncopeptides

Development and Regulatory status

Phase III Clinical Trials
Recommended for approval (Positive opinion)
Pre-registration (Filed)
Yes
Yes
Jun 22Recommended for EU approval by CHMP for use “ in combination with dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least three prior lines of therapies, whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one anti-CD38 monoclonal antibody, and who have demonstrated disease progression on or after the last therapy. For patients with a prior autologous stem cell transplantation, the time to progression should be at least 3 years from transplantation”. Pepaxti will be available as a 20 mg powder for concentrate for solution for infusion [15].
Jan 22A press release announces Oncopeptides has contacted the US FDA and rescinded their Oct 2021 letter requesting voluntary withdrawal of the NDA of Pepaxto (melphalan flufenamide) in the US. Further review and analyses of the Overall Survival data from the PIII OCEAN study and other relevant trials have led the company to reconsider its previous voluntary withdrawal request. Oncopeptides has discontinued the marketing of Pepaxto in the US and does not intend to market Pepaxto in the US at this time. The company has initiated a dialogue with the FDA to review the new data [14].
Dec 21NICE suspends development of its appraisal of Ygalo following discussion with the company; plans for UK availability now uncertain [12].
Oct 21The application to the EMA for a potential Conditional Marketing Authorization of melflufen (melphalan flufenamide) in the EU, based on the pivotal PII HORIZON study in relapsed refractory multiple myeloma, remains pending. The company expects to receive a CHMP opinion in Q2 2022 [13].
Oct 21Oncopeptides withdraw melphalan from US market as FDA do not consider PIII OCEAN study meets criteria of a confirmatory study [11].
Jul 21In the US, the FDA has issued a safety update on increased risk of death shown with melphalan flufenamide in the OCEAN trial. Oncopeptides AB were required to conduct OCEAN trial as a post-approval requirement under the Accelerated Approval program. Due to detrimental effect on overall survival, the FDA is requiring the manufacturer suspend enrolment in the trial and has also suspended enrolment in other ongoing trials with the drug [10].
Apr 21Filed in EU [6].
Mar 21Launched in US [9].
Feb 21Approved in US under Accelerated Approval program [8].
Jun 20Filed in US for use in adult patients whose disease is refractory to ≥1 proteasome inhibitor, 1 immunomodulatory agent and 1 anti-CD38 monoclonal antibody [5].
Nov 18Has orphan drug status in US [4].
Mar 15Granted orphan drug status in EU [3].

Category

Prodrug of melphalan and an alkylating peptide that stimulates caspase-3 and inhibits DNA synthesis
The incidence in Europe is 4.5-6.0 per 100,000/year with a mortality rate of 4.1 per 100,000/year [1].
Relapsed or refractory multiple myeloma (MM) in adults - with dexamethasone after three prior regimens (inc. lenalidomide and a proteasome inhibitor)
Intravenous infusion

Further information

Yes

Trial or other data

Sep 20PIII OCEAN is ongoing but has finished recruiting; collection of primary outcome data is due to complete Mar 21 [5].
Nov 19PIII OCEAN study is recruiting; collection of primary outcome data on course to complete in Dec [4].
Nov 18Other supportive studies for the licence application include PII OP-12-M1 (NCT01897714), PII OP-106 HORIZON (NCT02963493), OP-104 ANCHOR (NCT03481556) and PII OP-107 BRIDGE [3].
Nov 18PIII OCEAN study is still recruiting [2].
Jan 17PIII OCEAN trial to investigate the efficacy and safety of melphalan flufenamide plus dexamethasone versus pomalidomide plus dexamethasone in patients with relapsed, refractory multiple myeloma who are refractory lenalidomide starts (OP-103; NCT03151811). The trial is recruiting 450 patients in the US & EU (including UK). Collection of primary outcome data due to complete Dec 19 [2].

Evidence based evaluations

Pepaxti (EU), Pepaxto (US) Relapsed or refractory multiple myeloma (MM) in adults - with dexamethasone after two lines of therapy (inc. lenalidomide)

Information

Pepaxti (EU), Pepaxto (US)
Licence extension / variation
Oncopeptides
Oncopeptides

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Discontinued
Yes
Yes

Category

Prodrug of melphalan and an alkylating peptide that stimulates caspase-3 and inhibits DNA synthesis
The incidence in Europe is 4.5-6.0 per 100,000/year with a mortality rate of 4.1 per 100,000/year [1].
Relapsed or refractory multiple myeloma (MM) in adults - with dexamethasone after two lines of therapy (inc. lenalidomide)
Intravenous infusion

Further information

Yes