Clovis Oncology Announces Reimbursement for Rubraca® (rucaparib) Tablets for Women with Relapsed Ovarian Cancer in Italy

Clovis Oncology, Inc. (NASDAQ: CLVS) today announced that the Italian Medicines Agency (AIFA) has approved rucaparib for reimbursement in Italy. Rucaparib will soon be available as an option for monotherapy maintenance treatment for adults with relapsed, platinum-sensitive high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer that has responded to platinum-based chemotherapy.³

Rucaparib is indicated for eligible patients regardless of BRCA status, which means it can be prescribed for women who harbor a BRCA mutation or who are BRCA wild-type.³

“We very much welcome the arrival of the PARP inhibitor rucaparib, which offers a new treatment option after surgery and two lines of chemotherapy to all eligible women affected by relapsed ovarian cancer,” declared Nicoletta Cerana, National President of Acto Onlus, the number one Italian network of patient associations involved in the fight against ovarian cancer and gynecological tumors. “Ovarian cancer is a highly lethal neoplasm which now, thanks to the PARP inhibitors, can finally be made chronic. Patients know this and are ready to embark upon the difficult journey towards chronicity. As an association, we therefore hope that rucaparib can be prescribed as soon as possible in all Italian regions.”

Approximately 5,000 women are diagnosed with ovarian cancer in Italy every year, which equates to roughly 14 every day, and accounts for about 30 percent of all malignant tumors of the female reproductive system.^4,5 In addition, approximately 25 percent of patients harbor a BRCA1/2 mutation correlating to responsiveness to therapy, while the majority of women who are diagnosed are BRCA wild-type will have a worse prognosis and limited therapeutic options.^5,6,7 Despite advancements in treatment and care, more than 3,000 women still die each year.⁴ The 5-year survival rate for ovarian cancer in Italy is only 39 percent, falling to 31 percent at 10 years.⁵ Of those treated with surgery and first line chemotherapy, approximately 70 percent of patients will relapse within the first three years.⁸

“On a personal level, I am very pleased to be able to offer rucaparib to Italian patients as well, as this represents an important innovation,” said Nicoletta Colombo, Director of the Oncological Gynecology Program of the European Institute of Oncology in Milan and Associate Professor at the University of Milano-Bicocca. “In the ARIEL3 study, in fact, rucaparib doubled disease-free time after a second line of chemotherapy compared to placebo and with a manageable tolerability profile despite a study population very similar to clinical practice, regardless of the BRCA mutation.”

The European Union (EU) authorization is based on data from the pivotal phase 3 ARIEL3 clinical trial, which found that rucaparib significantly improved PFS in all ovarian cancer patient populations studied.¹ ARIEL3 successfully achieved its primary endpoint of extending investigator-assessed PFS versus placebo in all patients treated (intention-to-treat, or ITT), population, regardless of BRCA status (median 10.8 months vs 5.4 months).^1,2 In addition, it successfully achieved the key secondary endpoint of extending PFS by independent radiological review versus placebo in all patients treated (ITT), regardless of BRCA status (median 13.7 months vs 5.4 months).² The overall safety profile of rucaparib is based on data from 937 patients with ovarian cancer treated with rucaparib monotherapy in clinical trials.²

“In ovarian cancer, around 80 percent of cases involve women without a BRCA mutation and are characterized by a particularly poor prognosis,” explains Professor Sandro Pignata, Director of Medical Oncology of the Urogynecology Department at the National Oncological Institute Pascale Foundation cancer center in Naples, Scientific Coordinator of the Campania Region Oncology Network and President of the MITO Research Group. “The fact that rucaparib is a reimbursable drug makes it an important new treatment option, even for these patients who still too often do not receive safe and effective maintenance therapy.”

“The reimbursement of Rubraca in Italy is an important step in the ovarian cancer treatment pathway, as it has shown to be effective across a broad population of women with relapsed ovarian cancer,” said Patrick J. Mahaffy, President and CEO of Clovis Oncology. “We are working to make Rubraca available to as many eligible patients as possible across Europe, and we look forward to additional country launches in the coming months.”

About Rubraca^® (rucaparib)

Rubraca is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 that is being developed in multiple tumor types, including ovarian and metastatic castration-resistant prostate cancer (mCRPC), as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway.

Rubraca^® (rucaparib) European Union (EU) authorized use and Important Safety Information

Rubraca is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

Rubraca is indicated as monotherapy treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with ≥2prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

Efficacy of Rubraca as treatment for relapsed or progressive EOC, FTC, or PPC has not been investigated in patients who have received prior treatment with a PARP inhibitor. Therefore, use in this patient population is not recommended.

Rubraca^® (rucaparib) European Union (EU) authorized use and Important Safety Information

Rubraca is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

Rubraca is indicated as monotherapy treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with ≥2prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

Efficacy of Rubraca as treatment for relapsed or progressive EOC, FTC, or PPC has not been investigated in patients who have received prior treatment with a PARP inhibitor. Therefore, use in this patient population is not recommended.

Summary warnings and precautions:

Hematological toxicity

During treatment with Rubraca, events of myelosuppression (anemia, neutropenia, thrombocytopenia) may be observed and are typically first observed after 8–10 weeks of treatment with Rubraca. These reactions are manageable with routine medical treatment and/or dose adjustment for more severe cases. Complete blood count testing prior to starting treatment with Rubraca, and monthly thereafter, is advised. Patients should not start Rubraca treatment until they have recovered from hematological toxicities caused by previous chemotherapy (CTCAE grade ≥1).

Supportive care and institutional guidelines should be implemented for the management of low blood counts for the treatment of anemia and neutropenia. Rubraca should be interrupted or dose reduced according to Table 1 (see Posology and Method of Administration [4.2] of the Summary of Product Characteristics [SPC]) and blood counts monitored weekly until recovery. If the levels have not recovered to CTCAE grade 1 or better after 4 weeks, the patient should be referred to a hematologist for further investigations.

MDS/AML

MDS/AML, including cases with fatal outcome, have been reported in patients who received Rubraca. The duration of therapy with Rubraca in patients who developed MDS/AML varied from less than 1 month to approximately 28 months.

If MDS/AML is suspected, the patient should be referred to a hematologist for further investigations, including bone marrow analysis and blood sampling for cytogenetics. If, following investigation for prolonged hematological toxicity, MDS/AML is confirmed, Rubraca should be discontinued.

Photosensitivity

Photosensitivity has been observed in patients treated with Rubraca. Patients should avoid spending time in direct sunlight because they may burn more easily during Rubraca treatment; when outdoors, patients should wear a hat and protective clothing, and use sunscreen and lip balm with sun protection factor of 50 or greater.

Gastrointestinal toxicities

Gastrointestinal toxicities (nausea and vomiting) are frequently reported with Rubraca, and are generally low grade (CTCAE grade 1 or 2), and may be managed with dose reduction (refer to Posology and Method of Administration [4.2], Table 1 of the SPC) or interruption. Antiemetics, such as 5-HT3 antagonists, dexamethasone, aprepitant and fosaprepitant, can be used as treatment for nausea/vomiting and may also be considered for prophylactic (i.e. preventative) use prior to starting Rubraca. It is important to proactively manage these events to avoid prolonged or more severe events of nausea/vomiting which have the potential to lead to complications such as dehydration or hospitalization.

Embryofetal toxicity

Rubraca can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings from animal studies. In an animal reproduction study, administration of Rubraca to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicity at exposures below those in patients receiving the recommended human dose of 600 mg twice daily (see Preclinical Safety Data [5.3] of the SPC).

Pregnancy/contraception

Pregnant women should be informed of the potential risk to a fetus. Women of reproductive potential should be advised to use effective contraception during treatment and for 6 months following the last dose of Rubraca (see section 4.6 of the SPC). A pregnancy test before initiating treatment is recommended in women of reproductive potential.

Click here to access the current SPC. Healthcare professionals should report any suspected adverse reactions via their national reporting systems.

About Clovis Oncology

Clovis Oncology, Inc. is a biopharmaceutical company focused on acquiring, developing and commercializing innovative anti-cancer agents in the U.S., Europe and additional international markets. Clovis Oncology targets development programs at specific subsets of cancer populations, and simultaneously develops, with partners, for those indications that require them, diagnostic tools intended to direct a compound in development to the population that is most likely to benefit from its use. Clovis Oncology is headquartered in Boulder, Colorado, with additional office locations in the U.S. and Europe. Please visit www.clovisoncology.com for more information.

To the extent that statements contained in this press release are not descriptions of historical facts regarding Clovis Oncology, they are forward-looking statements reflecting the current beliefs and expectations of management. Examples of forward-looking statements contained in this press release include, among others, statements regarding our plans to launch Rubraca in additional European countries, including availability of Rubraca in Italy, and to make Rubraca available to additional eligible patients. Such forward-looking statements involve substantial risks and uncertainties that could cause our future results, performance or achievements to differ significantly from that expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the market potential of Rubraca, including the performance of our sales and marketing efforts and the success of competing drugs and therapeutic approaches, the performance of our third-party manufacturers and our distribution network, our clinical development programs for our drug candidates and those of our partners, and actions by the FDA, the EMA or other regulatory authorities regarding data required to support drug applications and whether to accept or approve drug applications that may be filed, as well as their decisions regarding drug labeling, reimbursement and pricing. Clovis Oncology does not undertake to update or revise any forward-looking statements. A further description of risks and uncertainties can be found in Clovis Oncology’s filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K and its reports on Form 10-Q and Form 8-K.

References

1. Coleman RL, et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017;390:1949–61.
2. Summary of Product Characteristics Rubraca 200, 250, 300 mg film-coated tablets. Available at: https://www.ema.europa.eu/en/documents/product-information/rubraca-epar-product-information_en.pdf. Accessed October 2019.
3. GU Serie Generale n.265 del 12-11-2019
4. World Health Organization. GLOBOCAN: estimated cancer incidence, mortality and prevalence worldwide in 2018. Available at http://gco.iarc.fr/. Accessed October 2019.
5. AIRTUM / AIOM Ovarian Cancer Guidelines. https://www.aiom.it/wp-content/uploads/2018/11/2018_LG_AIOM_Ovaio.pdf. Accessed October 2019.
6. Pennington KP et al. Clin Cancer Res 2014; 20: 764-775
7. Konstantinopoulos PA et al. Journal Clin Onco 2010; 22: 3555-3561
8. Ledermann J, et al. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013;24(suppl 6):vi24–32.

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