As of October 11th, Rubraca (Rucaparib) has been approved for NHS use by NICE in its final draft guidance (NICE, 2019). The drug, developed by the University of Newcastle, will benefit women with subtypes of Ovarian, Fallopian Tube and Peritoneal Cancer (Press Office, 2019). Ovarian Cancer is one of the most common cancers in the UK, with an average of 7470 new cases per year (Cancer Research UK, 2019). The drug will be available to patients who have previously responded to platinum-based chemotherapy (Press Office, 2019). Clinical trials had shown the drug to be effective in halving the rate at which tumours grow, from 5.4 months to 10.8 months (Clinicaltrials.gov, 2019). Crucially, Rucaparib is likely to reduce the frequency of chemotherapy sessions and the associated negative side effects.
The drug works by inhibiting the enzyme PARP-1, which is involved in tumour suppression by repairing damage to DNA. One such PARP-1 mediated repair pathway, known as Michrohomology-mediated end joining (MMEJ) is attributed with a high error rate when repairing double strand DNA breaks (Truong et al., 2013). In roughly 50% of Ovarian cancers, tumours show increased MMEJ activity and subsequent genome instability (Ceccaldi et al., 2015). Therefore, the inhibitory action of Rucaparib on TARP-1 targets tumour cells highly dependent on MMEJ, decreasing erroneous replication of DNA.
The approval of Rucaparib by NICE comes as a surprise just 2 months after its own refusal to recommend the treatment. On the 6th of August, NICE issued a draft guidance stating that there was insufficient clinical data on whether the treatment extended patient lifespan. To compound this reservation, NICE also felt the price of the drug did not meet NHS guidelines on what it deems cost effective (Pharmafile.com, 2019). In response to this, the manufacturer, Clovis Oncology consulted NICE and proposed a change in pricing structure. The twice a day tablet is now available as part of the Cancer Drugs Fund (NHS England, 2019) and will be monitored for its effectiveness in long term use (Pharmafile.com, 2019).
Cancer Research UK. (2019). Ovarian cancer statistics. [online] Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/ovarian-cancer [Accessed 21 Oct. 2019].
Ceccaldi, R., Liu, J., Amunugama, R., Hajdu, I., Primack, B., Petalcorin, M., O’Connor, K., Konstantinopoulos, P., Elledge, S., Boulton, S., Yusufzai, T. and D’Andrea, A. (2015). Homologous-recombination-deficient tumours are dependent on Polθ-mediated repair. Nature, 518(7538), pp.258-262.
Clinicaltrials.gov. (2019). A Study of Rucaparib as Switch Maintenance Following Platinum-Based Chemotherapy in Patients With Platinum-Sensitive, High-Grade Serous or Endometrioid Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancer - Full Text View - ClinicalTrials.gov. [online] Available at: https://clinicaltrials.gov/ct2/show/NCT01968213?term=NCT01968213&rank=1 [Accessed 21 Oct. 2019].
NICE. (2019). Another treatment option for ovarian cancer approved for the Cancer Drugs Fund. [online] Available at: https://www.nice.org.uk/news/article/another-treatment-option-for-ovarian-cancer-approved-for-the-cancer-drugs-fund [Accessed 21 Oct. 2019].
NHS England (2019). NHS England » Cancer Drugs Fund. [online] England.nhs.uk. Available at: https://www.england.nhs.uk/cancer/cdf/ [Accessed 21 Oct. 2019].
Pharmafile.com. (2019). NICE reject Clovis Oncology's ovarian cancer drug Rubraca | Pharmafile. [online] Available at: http://www.pharmafile.com/news/525807/nice-reject-clovis-oncologys-ovarian-cancer-drug-rubraca [Accessed 21 Oct. 2019].
Pharmafile.com. (2019). Clovis Oncology's Rubraca now available via the Cancer Drugs Fund for ovarian, peritoneal, fallopian tube cancer | Pharmafile. [online] Available at: http://www.pharmafile.com/news/530779/clovis-oncologys-rubraca-now-available-cancer-drugs-fund-ovarian-peritoneal-fallopian-tu [Accessed 21 Oct. 2019].
Press Office. (2019). New ovarian cancer drug now available on the NHS. [online] Available at: https://www.ncl.ac.uk/press/articles/latest/2019/10/rubracanhsapproval/ [Accessed 21 Oct. 2019].
Truong, L., Li, Y., Shi, L., Hwang, P., He, J., Wang, H., Razavian, N., Berns, M. and Wu, X. (2013). Microhomology-mediated End Joining and Homologous Recombination share the initial end resection step to repair DNA double-strand breaks in mammalian cells. Proceedings of the National Academy of Sciences, 110(19), pp.7720-7725.
Pharmaceutical Pricing Analyst