Talquetamab, sold under the brand name Talvey, is a

humanized monoclonal antibody Humanized antibodies are antibodies from non-human species whose protein sequences have been modified to increase their similarity to antibody variants produced naturally in humans. The process of "humanization" is usually applied to monoclonal ant ...

used for the treatment of

multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibody, antibodies. Often, no symptoms are noticed initially. As it progresses, bone ...

. It is a bispecific GPRC5D-directed CD3 T-cell engager. Talquetamab is a bispecific antibody against two targets: human CD3, a

T-cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their ce ...

surface

antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

, and human G-protein coupled receptor family C group 5 member D (GPRC5D), a tumor-associated antigen with potential antineoplastic activity. Talquetamab binds both targets, drawing the T cells close to the tumor cells, causing a cytotoxic T-lymphocyte response. It is being developed by

Janssen Pharmaceuticals Johnson & Johnson Innovative Medicine (formerly Janssen Pharmaceuticals) is a Belgian pharmaceutical company headquartered in Beerse, Belgium, and wholly owned by Johnson & Johnson. It was founded in 1953 by Paul Janssen. In 1961, Janssen Ph ...

. The most common adverse reactions include

cytokine release syndrome In immunology, cytokine release syndrome (CRS) is a form of systemic inflammatory response syndrome (SIRS) that can be triggered by a variety of factors such as infections and certain drugs. It refers to cytokine storm syndromes (CSS) and occur ...

dysgeusia Dysgeusia, also known as parageusia, is a distortion of the sense of taste. Dysgeusia is also often associated with ageusia, which is the complete lack of taste, and hypogeusia, which is a decrease in taste sensitivity. An alteration in taste or ...

, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, decreased weight, dry mouth,

pyrexia Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with body temperature exceeding the normal range caused by an increase in the body's temperature set point in the hypothalamus. There is no single agre ...

, xerosis,

dysphagia Dysphagia is difficulty in swallowing. Although classified under " symptoms and signs" in ICD-10, in some contexts it is classified as a condition in its own right. It may be a sensation that suggests difficulty in the passage of solids or l ...

, upper respiratory tract infection, and diarrhea. Talquetamab was approved for medical use in both the United States and the European Union in August 2023. The US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) considers it to be a

first-in-class medication A first-in-class medication is a prototype drug that uses a "new and unique mechanism of action" to treat a particular medical condition. While the Food and Drug Administration's Center for Drug Evaluation and Research tracks first-in-class medic ...

Medical uses

Talquetamab is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the treatment of adults with relapsed or refractory multiple myeloma who have received prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Adverse effects

The US

(FDA) label prescribing information has a

boxed warning In the United States, a boxed warning (sometimes "black box warning", colloquially) is a type of warning that appears near the beginning of the package insert for certain prescription drugs, so called because the U.S. Food and Drug Administratio ...

for life-threatening or fatal cytokine release syndrome and neurologic toxicity, including immune effector cell-associated neurotoxicity.

Structure

In 2024, the molecular structure of GPRC5D complexed with talquetamab Fab (anti GPRC5D) were characterized by using cryogenic electron microscopy. Structural analysis of the complex has revealed that talquetamab Fab lodges at a shallow pocket on the extracellular surface of GPRC5D and recognizes ECLs and TM3/5/7 of one GPRC5D protomer via six CDRs.

History

Efficacy was evaluated in MMY1001 (MonumenTAL-1) (NCT03399799, NCT04634552), a single-arm, open-label, multicenter study that included 187 participants who had previously received at least four prior systemic therapies. Participants received talquetamab-tgvs 0.4 mg/kg subcutaneously weekly, following two step-up doses in the first week of therapy, or talquetamab-tgvs 0.8 mg/kg subcutaneously biweekly (every two weeks), following three step-up doses, until disease progression or unacceptable toxicity. The main efficacy outcome measures were overall response rate and duration of response as assessed by an independent review committee using IMWG criteria. The primary efficacy population consisted of participants who had previously received at least four prior lines of therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Overall response rate in the 100 participants receiving 0.4 mg/kg weekly was 73% (95% confidence interval (CI): 63.2%, 81.4%) and median duration of response was 9.5 months (95% CI: 6.5, not estimable). Overall response rate in the 87 participants receiving 0.8 mg/kg biweekly was 73.6% (95% CI: 63%, 82.4%) and median duration of response was not estimable. An estimated 85% of responders maintained response for at least nine months. The FDA granted the application for talquetamab

priority review Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program ...

breakthrough therapy Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "b ...

, and

orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...

designations.

Society and culture

Legal status

In the United States, Janssen received

designation for talquetamab in June 2022, for the treatment of adults with relapsed or refractory multiple myeloma, who have previously received at least four prior lines of therapy, including a

proteasome inhibitor Proteasome inhibitors (INN stem ) are drugs that block the action of proteasomes. Proteasomes are large proteins complexes that are used to break down other proteins. These inhibitors are being studied for the treatment of cancer. Drugs such as ...

, an immunomodulatory agent, and an anti-

CD38 CD38 (cluster of differentiation 38), also known as cyclic ADP ribose hydrolase, is a glycoprotein found on the surface of many immune cells (white blood cells), including CD4+, CD8+, B lymphocytes and natural killer cells. CD38 also functions in ...

antibody. Janssen filed for approval from the FDA in December 2022, and from the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

in January 2023. On 20 July 2023, the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as the Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regar ...

(CHMP) of the

(EMA) adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Talvey, intended for the treatment of multiple myeloma. Talvey was reviewed under EMA's accelerated assessment program. The applicant for this medicinal product is Janssen-Cilag International N.V. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Talquetamab was approved for medical use in the European Union in August 2023.

References

External list

* * {{Authority control Monoclonal antibodies for tumors Orphan drugs