Talquetamab gains EC approval for use in relapsed/refractory multiple myeloma

24th August 2023

Talquetamab has been granted a conditional marketing authorisation by the European Commission as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma.

Talquetamab (brand name Talvey) is approved as a weekly or biweekly subcutaneous injection after an initial step-up phase. It can be used as monotherapy for the treatment of patients relapsed and refractory multiple myeloma who have had an inadequate response to at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody. They must also have demonstrated disease progression on the last treatment.

The treatment is a bispecific engaging antibody that binds to CD3, on the surface of T-cells, and G protein-coupled receptor class C group 5 member D (GPRC5D), a novel target highly expressed on the surface of multiple myeloma cells and hard keratinised tissues.

Multiple myeloma is a malignancy of terminally differentiated plasma cells that typically presents with bone marrow infiltration of clonal plasma cells and monoclonal protein in the serum and/or urine.

Commenting on the EC decision, Edmond Chan, senior director EMEA therapeutic area lead haematology, Janssen-Cilag Limited, said: ‘[This] brings a new off-the-shelf option, with a novel cellular target and the immediate option of biweekly dosing, to an area of high unmet clinical need.

‘The high overall response rates in patients with heavily pretreated multiple myeloma, including those with prior T-cell redirection therapy, are encouraging, and we believe talquetamab has the potential to offer physicians flexibility and versatility when determining the optimal treatment regimen for their patients.‘

The EC approval follows a similar FDA approval in the US in August 2023.

Talquetamab clinical efficacy

The talquetamab approval was based on efficacy data from the phase 1 and phase 2 MonumenTAL-1 study. In the trial, patients had received a median of five prior lines of therapy and talquetamab was given at a weekly dose of 0.4 mg/kg or biweekly 0.8 mg/kg.

For both dosage regimens, patients showed meaningful overall response rates. After a median follow-up of 12.7 months, 71.7% of response-evaluable patients treated at the 0.8 mg/kg biweekly dose achieved a response. Some 60.8% achieved a very good partial response (VGPR) or better and 38.7% achieved a complete response (CR) or better.

After a median follow-up of 18.8 months, 74.1% of response-evaluable patients treated with the 0.4 mg/kg weekly dose of talquetamab achieved a response; 59.5% a VGPR or better and 33.6% achieved a CR or better.

An estimated 76.3% and 51.5% of patients maintained a response for at least nine months at the 0.8 mg/kg biweekly and 0.4 mg/kg weekly talquetamab doses, respectively.

Maria-Victoria Mateos, consultant physician in haematology at the University Hospital of Salamanca in Spain, said: ‘As multiple myeloma progresses and patients cycle through treatments, the disease becomes
more difficult to treat and remission periods shorten. Targeting GPRC5D has been shown to deliver deep responses, and unlike many other targets for multiple myeloma, its expression is limited on immune cells providing an important new approach to targeting this heterogenous disease.‘

Taldefgrobep alfa granted orphan drug designation for spinal muscular atrophy in the EU

2nd August 2023

Taldefgrobep alfa has been given orphan medicinal product designation from the European Commission (EC) for the treatment of spinal muscular atrophy (SMA).

A novel anti-myostatin adnectin, the drug has the potential to deliver significant benefits for people with SMA by enhancing muscle function when used in combination with currently available disease modifying therapies that help preserve motor neurons.

Myostatin is a naturally occurring protein that limits skeletal muscle growth and the inhibition of the protein is a promising therapeutic strategy for SMA.

Taldefgrobep alfa’s novelty in a field of myostatin inhibitors is based on its unique, dual mechanism of action. It binds to myostatin to lower overall myostatin levels and also functions as a receptor antagonist, thereby blocking myostatin signalling in skeletal muscles.

The first treatment to be approved by the EU for SMA was nusinersen back in 2017, which was administered via an intrathecal injection. The first oral therapy, risdiplam (brand name Evrysdi) was approved in 2021.

Expressing his delight about the orphan drug designation, Irfan Qureshi, chief medical officer at Biohaven, said: ‘Children and adults living with SMA experience significant muscle weakness and functional impairments affecting their quality of daily life, and a substantial unmet medical need persists. We are excited about the potential for taldefgrobep alfa to improve the lives of patients and families affected by SMA.‘

Biohaven is currently enrolling a Phase 3 clinical trial of taldefgrobep alfa to evaluate its efficacy and safety in participants with SMA.

Taldefgrobep alfa previously received fast track and orphan drug designation in the US.

Spinal muscular atrophy prevalence

SMA is a rare, genetic neurodegenerative disorder characterised by the loss of motor neurons, atrophy of the voluntary muscles of the limbs and trunk, and progressive muscle weakness that is often fatal. Typically diagnosed in young children, the condition is caused by insufficient production of the survival of motor neuron (SMN) protein, which is essential for the survival of motor neurons, and encoded by two genes: SMN1 and SMN2. The condition affects approximately one in 10,000 live births globally, with an estimated incidence in Europe ranging from one in 3,900 to one in 16,000 live births.

Orphan drug designation is only permitted for the treatment, prevention or diagnosis of a disease that is life-threatening or chronically debilitating and where the prevalence in the EU is less than five in 10,000 and where the medicine offers significant benefit to those with the condition.