|Other names||IMC-3G3, LY-3012207|
|Drug class||PDGFR-α Inhibitors|
|Elimination half-life||11 days|
|Chemical and physical data|
|Molar mass||147241.21 g·mol−1|
Common side effects included nausea, tiredness, low white blood cells, pain, low platelets, abdominal pain, low potassium, headache, swelling, and allergic reactions. It is a monoclonal antibody which inhibits platelet-derived growth factor receptor alpha.
Olaratumab was approved for medical use in the United States and Europe in 2016. In 2019 it was withdrawn from market due to lack of benefit. It was sold for about 2,600 USD for 500 mg in the United States.
Olaratumab was used in combination with doxorubicin for the treatment of adults with advanced soft-tissue sarcoma (STS) who cannot be cured by cancer surgery or radiation therapy, and who have not been previously treated with doxorubicin.
In a randomised controlled trial of 133 people with STS, olaratumab plus doxorubicin improved the median of progression-free survival from 4.1 to 6.6 months as compared to doxorubicin alone but this was not significant, and overall survival from 14.7 to 26.5 months which was.
However, a phase 3 trial did not find any advantage in adding olaratumab to doxorubicin. Therefore, in January 2019, FDA and EMA decided to recommend not starting olaratumab for soft tissue sarcoma. In April 2019 the European Medicines Agency requested the marketing authorisation be revoked. Shortly afterwards the German Physician's Medicines Commission reported that olaratumab will be removed from the German market "in a few weeks" and asked doctors not to treat new patients outside of clinical trials. Lilly subsequently voluntarily withdrew in the United States.
In studies, the most serious side effects of the combination olaratumab/doxorubicin were neutropenia (low count of neutrophil white blood cells) with a severity of grade 3 or 4 in 55% of patients, and musculoskeletal pain grade 3 or 4 in 8% of patients. Common milder side effects were lymphopenia, headache, diarrhoea, nausea and vomiting, mucositis, and reactions at the infusion site; all typical effects of cancer therapies.
No pharmacokinetic interactions with doxorubicin were observed in studies. Being a monoclonal antibody, olaratumab is neither metabolised by cytochrome P450 liver enzymes nor transported by transmembrane pumps, and is thus not expected to interact relevantly with other drugs.
Mechanism of action
Olaratumab was originally developed by ImClone Systems, which was acquired by Eli Lilly in 2008. A Phase I clinical trial was conducted in Japanese patients in September 2010, followed by a Phase II trial in 133 patients, starting in October 2010.
In February 2015, the European Medicines Agency assigned olaratumab orphan drug status for the treatment of soft-tissue sarcoma. The European Commission granted a conditional marketing authorisation, based on the mentioned Phase II study, valid throughout the European Union on 9 November 2016.
Previously considered a promising drug, the FDA granted olaratumab fast track designation, breakthrough therapy designation and priority review status. In October 2016, the US FDA issued an accelerated approval notice for use of olaratumab with doxorubicin to treat adults with certain types of soft-tissue sarcoma, based on the same study.
A Phase III trial completed in 2019, and unfortunately showed no benefit from the addition of olaratumab to doxorubicin. As noted above, these results led to withdrawal of approval in the United States and Europe.
- "Olaratumab Monograph for Professionals". Drugs.com. Retrieved 7 November 2021.
- "Lartruvo". Archived from the original on 25 September 2020. Retrieved 7 November 2021.
- "Lartruvo Prices, Coupons & Patient Assistance Programs". Drugs.com. Retrieved 7 November 2021.
- "EPAR – Product information for Lartruvo" (PDF). European Medicines Agency. 23 November 2016. Archived (PDF) from the original on 17 March 2018. Retrieved 19 March 2021.
- "FDA grants accelerated approval to new treatment for advanced soft tissue sarcoma". US FDA. 19 October 2016. Archived from the original on 23 April 2019. Retrieved 19 March 2021.
- Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, et al. (July 2016). "Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial". Lancet. 388 (10043): 488–97. doi:10.1016/S0140-6736(16)30587-6. PMC 5647653. PMID 27291997.
- "FDA, EMA Recommend Against Starting Olaratumab for Soft Tissue Sarcoma". OncLive. Archived from the original on 22 April 2019. Retrieved 19 March 2021.
- "EMA recommends withdrawal of marketing authorisation for cancer medicine Lartruvo" (PDF). Archived (PDF) from the original on 26 November 2020. Retrieved 19 March 2021.
- "Drug Safety Mail 2019-25 by Arzneimittelkommission der Deutschen Ärzteschaft (in German)". 7 May 2019. Archived from the original on 7 May 2019. Retrieved 19 March 2021.
- "FDA Purple Book Data". U.S. Food and Drug Administration. August 2020. Archived from the original on 26 October 2020. Retrieved 23 September 2020.
- "Imclone legacy drug gains green light for Lilly in soft tissue sarcoma". BioWorld. Archived from the original on 1 January 2017. Retrieved 31 December 2016.
- Doi T, Ma Y, Dontabhaktuni A, Nippgen C, Nippgen J, Ohtsu A (July 2014). "Phase I study of olaratumab in Japanese patients with advanced solid tumors". Cancer Science. 105 (7): 862–9. doi:10.1111/cas.12444. PMC 4317910. PMID 24816152.
- Clinical trial number NCT01185964 for "A Study of IMC-3G3 in Soft Tissue Sarcoma" at ClinicalTrials.gov
- "Orphan Designation for olaratumab". European Medicines Agency. 9 April 2015. Archived from the original on 5 May 2016. Retrieved 14 March 2022.
- "EPAR summary for the public for Lartruvo" (PDF). European Medicines Agency. 23 November 2016. Archived (PDF) from the original on 17 March 2018. Retrieved 19 March 2021.
- Shirley M (January 2017). "Olaratumab: First Global Approval". Drugs. 77 (1): 107–112. doi:10.1007/s40265-016-0680-2. PMID 27995580. S2CID 3604814. Archived from the original on 26 October 2021. Retrieved 19 March 2021.
- Clinical trial number NCT02451943 for "A Study of Doxorubicin Plus Olaratumab (LY3012207) in Participants With Advanced or Metastatic Soft Tissue Sarcoma (ANNOUNCE)" at ClinicalTrials.gov