Pertuzumab
Humanized (from mouse) | |
| Target | HER2 |
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| Clinical data | |
| Trade names | Perjeta |
| Other names | 2C4 |
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Intravenous | |
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Pertuzumab, sold under the brand name Perjeta, is a
Side effects in more than half the people taking it include diarrhea, hair loss, and loss of neutrophils; more than 10% experience loss of red blood cells, hypersensitivity or allergic reaction, infusion reactions, decreased appetite, insomnia, distortions in the sense of taste, inflammation of the mouth or lips, constipation, rashes, nail disease, and muscle pain.[3] Women who are pregnant or planning on getting pregnant should not take it, it was not studied in people with certain heart conditions and should be used in caution in such people, and it should not be used with an anthracycline.[3] It is unknown if pertuzumab interacts with doxorubicin.[3]
It is the first-in-class of a kind of drug called a "
It was discovered and developed by Genentech and was first approved in 2012.[7][8]
Medical uses
Pertuzumab is administered as an intravenous infusion in combination with
As of 2016[update], pertuzumab has not been studied in people with a
Women of child-bearing age should use contraception while taking pertuzumab; it may damage the fetus in pregnant women, and it may be secreted in breast milk.[3]
Adverse effects
In clinical trials of the three-agent combination therapy in metastatic breast cancer, adverse effects occurring in more than half the people taking it included diarrhea, hair loss, and
In clinical trials of the neoadjuvant use of the combination, more than 50% of people had hair loss and loss of neutrophils.[3]
In both uses, more than 10% of people additionally experienced: loss of red blood cells, hypersensitivity or allergic reaction, infusion reactions, decreased appetite, insomnia, distortions in the sense of taste, inflammation of the mouth or lips, constipation, rashes, nail disease, and muscle pain.[3]
Pharmacology
The metabolism of pertuzumab has not been directly studied; in general antibodies are cleared principally by catabolism. The median clearance of pertuzumab was 0.235 liters/day and the median half-life was 18 days.[3]
Mechanism of action
Like many receptors, HER2 normally combines another protein in order to function (a process called
The epitope for pertuzumab is the domain of HER2 where it binds to HER3, and pertuzumab prevents the HER2/HER3 dimer from forming, which blocks signalling by the dimer.[6][10] Trastuzumab is another monoclonal antibody against HER2; its epitope is the domain where HER2 binds to another HER2 protein.[6] The two mAbs together prevent HER2 from functioning.[6]
Chemistry and manufacturing
Pertuzumab is an immunoglobulin G1 with a variable region against the human HER2 protein, a human-mouse monoclonal 2C4 heavy chain, disulfide bound with a human-mouse monoclonal 2C4 κ-chain.[11]
It is manufactured recombinantly in
History
The monoclonal antibody 2C4 appears to have first been published in 1990 by scientists from Genentech,
By 2003, Genentech understood that 2C4 prevented HER2 dimerizing with other HER receptors and had begun Phase I trials, aiming for a broad range of cancers, not just ones overexpressing HER2. It was the first known HER dimerization inhibitor.[14]
In 2005, Genentech presented poor results of Phase II trials of pertuzumab as a single agent in prostate, breast, and ovarian cancers, and said that it intended to continue developing it in combination with other drugs for ovarian cancer.[15][16]
In 2007, Genentech dropped the trade name Omnitarg.[17][18]
In March 2009, Roche acquired Genentech.[19][20]
In 2012, the results were published of the CLEOPATRA trial, a randomized placebo-controlled Phase III trial of pertuzumab in combination with trastuzumab and docetaxel in HER2-positive metastatic breast cancer.[21] Pertuzumab received US FDA approval for the treatment of HER2-positive metastatic breast cancer later that year.[8] Results of a Phase II trial in the neoadjuvant setting, NeoSphere, published in 2012,[22] and results of a Phase II cardiac safety study in the same population, Tryphaena, published in 2013.[23] The FDA approved the neoadjuvant indication in 2013.[24]
Pertuzumab was approved for medical use in the European Union in 2013.[3][5]
Society and culture
Economics
As of 2016[update], in the US each cycle of the three-drug combination given every three weeks costs around US$8,500, not including ancillary care costs.[25]
In the UK, a
References
- ^ a b https://www.guildlink.com.au/gc/ws/ro/pi.cfm?product=ropperje11013 [bare URL]
- FDA. Retrieved 22 October 2023.
- ^ a b c d e f g h i j k l m n o "Perjeta 420 mg Concentrate for Solution for Infusion - Summary of Product Characteristics (SmPC)". (emc). 2 July 2021. Retrieved 3 January 2022.
- ^ a b c d e "Perjeta- pertuzumab injection, solution, concentrate". DailyMed. Retrieved 3 January 2022.
- ^ a b "Perjeta EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 3 January 2022.
- ^ PMID 24715843.
- ^ "Drug Approval Package: Perjeta (pertuzumab) Injection NDA #125409". U.S. Food and Drug Administration (FDA). 3 August 2012. Retrieved 3 January 2022.
- ^ a b "FDA approves Perjeta for type of late-stage breast cancer". U.S. Food and Drug Administration (FDA). 8 June 2012. Archived from the original on 1 November 2012. Retrieved 3 January 2022.
- PMID 23320171.
- PMID 15093533.
- ^ "Proposed INN: List 89" (PDF). WHO Drug Information. 17 (3). 2003.
- PMID 11406546.
- ^ Fisher LM (1 October 2000). "Genentech: Survivor Strutting Its Stuff". The New York Times.
- PMID 12908564.
- ^ "Press Release: Data From Omnitarg Clinical Program Presented at American Society of Clinical Oncology Meeting". Genentech. 15 May 2005. Archived from the original on 6 April 2017. Retrieved 2 November 2016.
- ^ "Genentech's Omnitarg fails in Phase II". Pharma Times. 16 May 2005.
- ^ "Correction: Letter from the Editor". Cancer Oncology News: 3. February 2012.
- ^ "Press release: Roche in the first half of 2007". Roche. 19 July 2007.
- ^ Morse A (10 May 2006). "Chugai Shares Post Healthy Gain On Prospects for Cancer Drug". The Wall Street Journal. Retrieved 26 September 2008.
- Genetic Engineering & Biotechnology News. 21 July 2008. Archived from the originalon 3 February 2009. Retrieved 26 September 2008.
- PMID 22149875.
- PMID 25848335.
- PMID 23704196.
- ^ "FDA approves Perjeta for neoadjuvant breast cancer treatment". U.S. Food and Drug Administration (FDA) (Press release). 30 September 2013. Archived from the original on 10 October 2013. Retrieved 3 January 2022.
- PMID 26351332.
- S2CID 8470253.
- ^ "Breast cancer (HER2 positive, metastatic) - pertuzumab (with trastuzumab and docetaxel) [ID523]". NICE. 1 September 2016. Retrieved 2 November 2016.
- ^ McKee S (20 May 2016). "NICE rejects Roche's breast cancer drug Perjeta". Pharma Times.
- ^ Yip A (22 November 2016). "NICE U-Turns and Backs Approval of Roche's Perjeta for HER2-Positive Breast Cancer". Pharmalive.
Further reading
- Dean L (2015). "Pertuzumab Therapy and ERBB2 (HER2) Genotype". In Pratt VM, McLeod HL, Rubinstein WS, et al. (eds.). Medical Genetics Summaries. PMID 28520364. Bookshelf ID: NBK315949.
