Polatuzumab vedotin

Polatuzumab vedotin (INN;[1] brand name Polivy; development codes DCDS4501A and RG7596) is an antibody-drug conjugate or ADC designed for the treatment of cancer.[2] The US Food and Drug Administration approved polatuzumab vedotin in June 2019 for treatment of diffuse large B-cell lymphoma when used in combination with bendamustine and rituximab.[3][4] The drug was developed by Genentech and Roche.

Polatuzumab vedotin
Monoclonal antibody
Type?
SourceHumanized (from mouse)
TargetCD79B
Clinical data
Trade namesPolivy
Other namesDCDS4501A, RG7596, polatuzumab vedotin-piiq
License data
Legal status
Legal status
Identifiers
CAS Number
PubChem SID
IUPHAR/BPS
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6670H10317N1745O2087S40
Molar mass149627.43 g·mol−1

Polatuzumab vedotin contains a humanized monoclonal antibody (mAb) targeting CD79b (B-cell antigen receptor complex-associated protein beta chain) conjugated to the dolastatin analog monomethyl auristatin E (MMAE) via a protease-cleavable linker (valine–citrulline; maleimidocaproylvaline-citrulline-p-aminobenzoyloxycarbonyl or MC-VC-PABC). The advantage of the citrulline-valine (VC) linker being used that it is highly stable in plasma.[5]

Mechanism of action

Upon administration, polatuzumab vedotin selectively binds to CD79b, a protein which is abundantly expressed on the surface of B-cells. Following internalization and proteolytic cleavage, MMAE binds to tubulin and inhibits its polymerization, resulting in G2/M phase arrest and tumor cell apoptosis.

Clinical trials

Polatuzumab vedotin is being investigated for use in treatment of other cancers. Scientists are conducing tests of its effectiveness against B-cell non-Hodgkin’s lymphoma [6] and for treatment of patients with relapsed or refractory follicular lymphoma.[7]

History

In June 2019, polatuzumab vedotin-piiq was approved in the United States in combination with the chemotherapy bendamustine and a rituximab product (a combination known as “BR”), to treat adult patients with diffuse large B-cell lymphoma (DLBCL) that has progressed or returned after at least two prior therapies.[3] Polatuzumab vedotin-piiq is a novel antibody-drug conjugate, and DLBCL is the most common type of non-Hodgkin lymphoma.[3]

The U.S. Food and Drug Administration (FDA) granted accelerated approval to polatuzumab vedotin-piiq in combination with BR.[3] Further clinical trials are required to verify and describe the clinical benefit of polatuzumab vedotin-piiq.[3]

The FDA approved polatuzumab vedotin-piiq based primarily on evidence from one clinical trial (NCT02257567)[8] that was conducted in the United States, Canada, Europe, and Asia.[4] Patients who participated in the trial had lymphoma that came back or did not improve after prior treatment.[4]

The FDA granted the application of polatuzumab vedotin-piiq breakthrough therapy designation, priority review designation, and orphan drug designation.[3]

The FDA granted the approval of Polivy to Genentech.[3]

References
  1. World Health Organization (2012). "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 108" (PDF). WHO Drug Information. 26 (4).
  2. Statement On A Nonproprietary Name Adopted By The USAN Council - Polatuzumab Vedotin, American Medical Association - Needs login/subscription.
  3. "FDA approves first chemoimmunotherapy regimen for patients with relapsed or refractory diffuse large B-cell lymphoma". U.S. Food and Drug Administration (FDA) (Press release). 10 June 2019. Archived from the original on 25 November 2019. Retrieved 24 November 2019. This article incorporates text from this source, which is in the public domain.
  4. "Drug Trials Snapshots: Polivy". U.S. Food and Drug Administration (FDA). 17 June 2019. Archived from the original on 25 November 2019. Retrieved 24 November 2019. This article incorporates text from this source, which is in the public domain.
  5. Polatuzumab vedotin (Drug Description)
  6. NCT01992653 (Clinical Trial / Polatuzumab Vedotin / DCDS4501A / RG-7596)
  7. NCT02257567 (Clinical Trial / Polatuzumab Vedotin / DCDS4501A / RG-7596)
  8. Clinical trial number NCT02257567 for "A Study of Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab or Obinutuzumab Plus Bendamustine in Participants With Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma" at ClinicalTrials.gov
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.