Bispecific antibodies pass reimbursement hurdle

Inflection point for blood cancer treatment landscape

Reimbursemetn criteria have been set for multiple myeloma treatments 'Tecvayli'·'Elrexfio'

For DLBCL, 'Epkinly' awaits to be considered for the Cancer Disease Review Committee (CDRC)…second attempt for 'Columvi'

(from left) bispecific antibodies

Major bispecific antibody therapies targeting hematologic cancers have successively cleared the first stage of reimbursement.

 

With patients who have failed prior therapies desperately needing new options, attention is focused on whether these new drugs with innovative-mechanism will secure insurance reimbursement.

 

According to industry sources on November 3, the Health Insurance Review & Assessment Service (HIRA) recently held its 8th Cancer Disease Review Committee (CDRC).

 

At the meeting, reimbursement criteria were established for two hematologic bispecific antibodies: Janssen's 'Tecvayli (teclistamab)' and 'Pfizer's Elrexfio (elranatamab).' Multiple myeloma is a blood cancer characterized by the proliferation of abnormal plasma cells, which are created in the bone marrow, throughout the body.

 

A relatively large number of treatments have emerged for this cancer type, with new drugs being approved for up to fifth-line treatment and beyond.

 

Besides bispecific antibodies, various CAR-T new drugs like 'Kymriah (tisagenlecleucel)' and 'Yescarta (axicabtagene ciloleucel)' also target this disease.

 

Due to exiting alternative like CAR-T had led to the assessment that reimbursement for bispecific antibodies would not be easy.

 

However, limitations of CAR-T therapies include complex manufacturing processes, the time delay of over a month until administration, and the requirement for patients to maintain a certain health condition.

 

Unlike these, bispecific antibodies are off-the-shelf anti-cancer drugs that work by simultaneously recognizing cancer cells and T-cells, activating the T-cells to indirectly eliminate the cancer cells.

 

BCMA is a protein expressed on the surface of B cells, and CD3 is expressed on the surface of T-cells.

 

Elrexfio and Tecvayli have a novel mechanism that induces myeloma cell death by targeting both.

 

Elrexfio demonstrated efficacy in the MagnetisMM-3 Phase 2 study in patients who had failed three or more prior therapies.

 

In the trial, Elrexfio showed an Objective Response Rate (ORR) of 61%, and the rate of maintained response at 15 months was confirmed to be 71%.

 

The median Overall Survival (OS) for the Elrexfio group was 24.6 months, and the median Progression-Free Survival (PFS) was 17.2 months.

 

Tecvayli was administered to 165 patients in the MajesTEC-1 Phase 2 study, resulting in an ORR of 63%, with a stringent Complete Response (sCR) of 32.7%, a Complete Response (CR) of 6.7%, and a Very Good Partial Response (VGPR) of 19.4%.

 

The median time to response was 1.2 months, and the duration of response was reported to be 18.4 months.

 

Bispecific antibodies for B-cell lymphoma also await to be reviewed

bispecific antibodies

Discussions on reimbursement for bispecific antibodies are also progressing in relapsed/refractory Diffuse Large B-cell Lymphoma (DLBCL), another type of hematologic cancer.

 

Among these, AbbVie's 'Epkinly (epcoritamab)' passed the CDRC in July, after its reimbursement criteria were established.

 

DLBCL is the most common B-cell lymphoma, accounting for about 40% of non-Hodgkin lymphomas, and has an aggressive nature with rapid progression.

 

The failure rate after first-line treatment reaches about 15%, and even patients who achieve CR have a relapse rate of 25% within 18 months.

 

Although existing CAR-T therapies are reimbursed and utilized, their application to elderly patients is limited due to treatment initiation delays and neurotoxicity (ICANS).

 

Thus, the demand for new treatments still exists.

 

Epkinly was evaluated in the EPCORE NHL-1 Phase 1/2 study, involving 167 patients with CD20-positive relapsed or refractory DLBCL who had received two or more prior lines of therapy.

 

The results showed an ORR of 62%, a CR of 39%, and a median Duration of Response (DOR) of 15.5 months.

 

bispecific antibody

Attention is also focused on the re-attempt for Roche's bispecific antibody, 'Columvi (glofitamab).' Columvi was submitted to the CDRC in December last year and July this year but failed to establish reimbursement criteria.

 

Columvi was submitted concurrently with Epkinly in December last year; however, Epkinly succeeded in passing the CDRC hurdle in June on its second attempt.

 

Since Columvi has expanded its indication to second-line DLBCL treatment in the U.S.

 

and Europe, Roche may be considering a simultaneous reimbursement application for both second- and third-line settings.

 

Columvi is a treatment with a maximum duration of 12 cycles, approximately 8 months, and has a defined end of treatment.

 

In clinical trials, Columvi showed a CR of 40%, an ORR of 52%, and a median DOR of 26.9 months for patients who achieved CR.

 

It also recorded a 67% CR maintenance rate at 18 months.