Astellas Receives Positive CHMP Opinion for XTANDI for Patients with Metastatic Hormone-Sensitive Prostate Cancer

Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa Ph.D., "Astellas") announced today the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending an additional indication for the oral once-daily therapy XTANDI TM (enzalutamide) for adult men with metastatic hormone-sensitive prostate cancer (mHSPC, also known as metastatic castration-sensitive prostate cancer or mCSPC). 1 Men diagnosed with mHSPC tend to have a poor prognosis, with a median survival of approximately 3-4 years, underscoring the need for new treatment options. 2

If approved by the European Commission (EC), enzalutamide will be the only oral treatment approved by the EC to treat three distinct types of advanced prostate cancer — non-metastatic and metastatic castration-resistant prostate cancer (CRPC) and mHSPC. ³ The CHMP decision is based on data from the pivotal Phase 3 ARCHES trial investigating enzalutamide in men with mHSPC. ⁴

"This positive opinion from the CHMP is testament to our continuing commitment to addressing unmet needs for men with advanced prostate cancer," said Andrew Krivoshik , M.D., Ph.D., Senior Vice President and Global Therapeutic Area Head, Oncology Development, Astellas. "We are excited to be another step closer to approval of enzalutamide for the treatment of men with metastatic hormone-sensitive prostate cancer in Europe ."

Data from the ARCHES trial showed that enzalutamide plus androgen deprivation therapy (ADT) significantly reduced the risk of radiographic progression or death by 61% versus placebo plus ADT in men with mHSPC (n=1,150; hazard ratio [HR]=0.39 [95% confidence interval (CI): 0.30-0.50]; P 4

The safety analysis of the ARCHES trial appears consistent with the safety profile of enzalutamide in previous clinical trials in CRPC. In ARCHES, Grade 3 or greater adverse events (AEs) (defined as severe/disabling or life-threatening) were similar for patients receiving both enzalutamide plus ADT and those who received placebo plus ADT (24.3% vs. 25.6%). ⁴

The positive opinion from the CHMP will now be reviewed by the EC, which has the authority to approve medicines for European Union member countries, as well as Iceland , Norway and Liechtenstein . ⁵

Enzalutamide is currently approved in the EU for the treatment of adult men with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) and adult men with metastatic castration-resistant prostate cancer (mCRPC) in whom chemotherapy is not yet clinically indicated, or following disease progression on or after docetaxel therapy. ³ In the U.S., enzalutamide is approved in non-metastatic and metastatic CRPC as well as metastatic castration-sensitive prostate cancer (mCSPC) also referred to as mHSPC. ⁶ In Japan, enzalutamide is indicated for the treatment of prostate cancer with distant metastasis, which includes mHSPC and CRPC. ^7,8

About metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
In men with prostate cancer, the disease is considered metastatic once the cancer has spread outside of the prostate gland to other parts of the body. Men are considered hormone- (or castration-) sensitive if their disease still responds to medical or surgical treatment to lower testosterone levels. mHSPC has a median survival of approximately 3–4 years for men starting treatment with ADT. ²

About XTANDI™ (enzalutamide)
Enzalutamide is currently indicated in the EU for: ³

• the treatment of adult men with high-risk non-metastatic castration-resistant prostate cancer (CRPC);
• the treatment of adult men with metastatic CRPC who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated; and
• the treatment of adult men with metastatic CRPC whose disease has progressed on or after docetaxel therapy.

Important Safety Information
For important Safety Information for enzalutamide please see the full Summary of Product Characteristics at: https://www.medicines.org.uk/emc/product/3203 .

About ARCHES
The company-sponsored, Phase 3, randomized, double-blind, placebo-controlled, multinational ARCHES trial (NCT02677896) enrolled 1,150 patients with mHSPC at sites in the U.S., Canada , Europe , South America , and the Asia-Pacific region. Patients in the trial were randomized to receive enzalutamide 160 mg daily or placebo and continued on a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist or had a history of bilateral orchiectomy. The primary endpoint of the trial was radiographic progression-free survival (rPFS) assessed by blinded independent central review. rPFS was defined as the time from randomization to radiographic disease progression at any time or death within 24 weeks after study drug discontinuation. Radiographic disease progression was defined by identification of two or more new bone lesions on a bone scan with confirmation (Prostate Cancer Working Group 2 criteria) and/or progression in soft tissue disease. Patients were stratified by volume of disease (low vs high) and prior docetaxel therapy for prostate cancer (no prior docetaxel, 1-5 cycles, or 6 prior cycles). ⁴

About Astellas
Astellas Pharma Inc., is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+ ^® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into value for patients. For more information, please visit our website at https://www.astellas.com/en .

About the Pfizer/Astellas Collaboration
In October 2009 , Medivation, Inc, which is now part of Pfizer (NYSE:PFE), and Astellas (TSE: 4503) entered into a global agreement to jointly develop and commercialize enzalutamide. The companies jointly commercialize enzalutamide in the United States and Astellas has responsibility for manufacturing and all additional regulatory filings globally, as well as commercializing enzalutamide outside the United States .

Astellas Cautionary Notes
In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.

Information about pharmaceutical products (including products currently in development) which is included in this press release is not intended to constitute an advertisement or medical advice.

References

¹ European Medicines Agency. Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) September 2019 . Available at: https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-22- 25-march-2021 . Last accessed March 2021 .

² Mottet N, et al. Updated Guidelines for Metastatic Hormone-sensitive Prostate Cancer: Abiraterone Acetate Combined with Castration Is Another Standard. Eur Urol. 2018;3:316-321.

³ European Medicines Authority. Summary of Product Characteristics: Xtandi 40 mg soft capsules. Available at: https://www.medicines.org.uk/emc/product/3203/smpc . Last accessed March 2021 .

⁴ Armstrong A, et al. Phase 3 study of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC): the ARCHES trial. J Clin Oncol. 2019;7:687.

⁵ European Medicines Agency. Authorization of medicines. Available at: https://www.ema.europa.eu/about-us/what-we-do/authorisation-medicines . Last accessed March 2021 .

⁶ Food and Drug Administration. Highlights of prescribing information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/203415s015lbl.pdf . Last accessed March 2021 .

⁷ Pharmaceuticals and Medical Devices Agency. Summary of Investigation Results Enzalutamide. Available at: https://www.pmda.go.jp/files/000232289.pdf . Last accessed March 2021.

⁸ Astellas Press Release. XTANDI® (enzalutamide) Approved by Japan MHLW for the Treatment of Prostate Cancer with Distant Metastasis. Available at: https://www.astellas.com/system/files/news/2020-05/20200529_en_1.pdf . Last accessed March 2021 .

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SOURCE Astellas Pharma Inc.