Significant Improvement in Overall Survival with ERLEADA®▼ (apalutamide) for Patients with Non-Metastatic Castration-Resistant Prostate Cancer

The Janssen Pharmaceutical Companies of Johnson & Johnson today announced results from the final analysis of the pivotal Phase 3 SPARTAN study demonstrating ERLEADA^®▼ (apalutamide) in combination with androgen deprivation therapy (ADT) significantly improved overall survival (OS), compared to ADT alone, in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) who were at high risk of developing metastases.¹ Results will be presented at the American Society of Clinical Oncology (ASCO) Virtual Scientific Programme (Abstract #5516) beginning on Friday 29^th May.¹

Findings from the study showed that apalutamide in combination with ADT prolonged median overall survival by 14 months and decreased the risk of death by 22 percent.¹ Median OS was significantly longer, with 73.9 months for patients receiving treatment with apalutamide in combination with ADT compared to 59.9 months with patients receiving placebo in combination with ADT [HR=0.78; p=0.0161 (to reach statistical significance, a p-value of p<0.046 needed to be observed)].¹ After the study met its primary endpoint of metastasis-free survival (MFS), the SPARTAN study was unblinded and patients on placebo were allowed to crossover to apalutamide. The OS results were achieved despite a crossover of 76 randomised placebo patients (19 percent) to apalutamide treatment.¹ After adjusting for the cross-over of patients in the placebo arm, the treatment effect of apalutamide plus ADT exceeded median OS compared to placebo plus ADT with a difference of 21 months between the two arms (73.9 months vs 52.8 months, respectively, HR=0.69, p=0.0002). Additionally, treatment with apalutamide in combination with ADT significantly delayed patients’ time to cytotoxic chemotherapy compared to placebo in combination with ADT (HR=0.63; p=0.0002).¹

“Treatment for patients with non-metastatic castration-resistant prostate cancer is primarily focused on delay of metastases and improvement of overall survival,” said Eric Small, M.D., FASCO, Professor of Medicine, and Chief Scientific Officer at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, and lead SPARTAN study investigator. “The final analysis of SPARTAN includes long-term data for each of these treatment parameters and helps to support the earlier use of apalutamide versus ADT alone.”

Together with data from the primary analysis, the SPARTAN study has met all primary, secondary and exploratory endpoints. The primary endpoint of the study was MFS; the secondary endpoints were time to metastasis, progression-free survival (PFS), time to symptomatic progression, OS and time to initiation of cytotoxic chemotherapy; and the exploratory endpoints were second progression-free survival (PFS2), PSA responses and risk of PSA progression.^1,2

“Our driving commitment to delay the onset of metastases and add years to life for prostate cancer patients has taken a significant step forward with today’s data,” said Dr Joaquín Casariego, M.D., Janssen Therapeutic Area Lead Oncology for Europe, Middle East & Africa, Janssen-Cilag S.A. “The SPARTAN trial has successfully demonstrated that apalutamide improved overall survival by an average of 14 months, reinforcing the need to treat earlier in prostate cancer for the benefit of patients and their families. At Janssen, our vision is to pioneer new approaches to treating cancer by thinking differently about diagnosis and looking towards intercepting the disease before it can even take a hold.”

Median treatment duration was nearly three times longer for patients treated with apalutamide plus ADT (33 months) compared with those treated with placebo plus ADT (12 months).¹ Grade 3/4 treatment-emergent adverse events of special interest were rash (5.2 percent), fractures (4.9 percent), falls (2.7 percent), ischemic heart disease (2.6 percent), hypothyroidism (0 percent) and seizures (0 percent). Safety and tolerability of apalutamide is consistent and as reported previously.^1,3

Initial results from the SPARTAN trial were presented at the 2018 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) and simultaneously published in The New England Journal of Medicine.^{2, 4} The study met its primary endpoint of MFS demonstrating a median MFS of more than two years (difference of 24.31 months) and a 72 percent reduction in risk of distant metastasis in patients with nmCRPC. ⁴ OS data were not mature at the time of the final MFS analysis (24 percent of the required number of events). Updated results were presented at the European Society for Medical Oncology (ESMO) Annual Congress in 2019 and were simultaneously published in Annals of Oncology .^5,6

#ENDS#

About the SPARTAN Study
SPARTAN (NCT01946204) is a Phase 3, randomised, registrational, double-blind, placebo-controlled, multicentre study that evaluated ERLEADA^® (apalutamide) in combination with ADT in men with nmCRPC with a rapidly rising PSA (PSA Doubling Time ≤10 months).^2,7 The SPARTAN study enrolled 1,207 patients who were randomised 2:1 to receive either apalutamide orally at a dose of 240 mg once daily in combination with ADT (n=806) or placebo once daily in combination with ADT (n=401).⁴

About Non-Metastatic Castration-Resistant Prostate Cancer
Non-metastatic castration-resistant prostate cancer (nmCRPC) refers to a disease stage in which the cancer no longer responds to treatments that lower testosterone but has not yet been discovered in other parts of the body using a total body bone scan and/or CT/MRI scan.⁸ Features include: lack of detectable metastatic disease using conventional radiographic imaging and rapidly rising PSA while on ADT with serum testosterone level below 50 ng/dL.^9,10 Ninety percent of patients with nmCRPC will eventually develop metastases, which can lead to pain, fractures and other symptoms.¹¹ The relative five-year survival rate for patients diagnosed with a distant-stage prostate cancer is 31 percent.¹² It is critical to delay the development of metastasis in patients with nmCRPC.

About ERLEADA ^®
ERLEADA^® (apalutamide) is an androgen receptor (AR) inhibitor indicated for use in Europe for the treatment of adult men with non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk of developing metastatic disease and in adult men for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy (ADT).⁷ In the U.S. apalutamide is indicated for the treatment of nmCRPC and mHSPC.¹³

Warnings and Precautions include ischemic heart disease, fractures, falls and seizure.^2,3 In the SPARTAN study, the most common adverse reactions (≥10 percent) were fatigue, hypertension, rash, diarrhoea, nausea, weight decreased, arthralgia, falls, hot flush, decreased appetite, fracture and peripheral edema.^1,4

About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.

Learn more at www.janssen.com/emea. Follow us at www.twitter.com/janssenEMEA for our latest news. Janssen Research & Development, LLC and Janssen-Cilag S.A. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

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Cautions Concerning Forward-Looking Statements

This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of ERLEADA^® (apalutamide) for the treatment of patients with non-metastatic castration-resistant prostate cancer. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations of the Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 29, 2019, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in the company’s most recently filed Quarterly Report on Form 10-Q, and the company’s subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

References

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¹ Small, E. et al. Final Survival Results From SPARTAN, a Phase 3 Study of Apalutamide (APA) vs Placebo (PBO) in Patients (pts) With Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC). ASCO 2020. Poster presentation (abstract #5516). Available at: https://s3.amazonaws.com/files.oncologymeetings.org/prod/s3fs-public/2020-05/AM20-GENITOURINARY-PROSTATE-TESTICULAR-AND-PENILE.pdf?null. Last accessed May 2020.
² Smith, MR. et al. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N Engl J Med. 2018 Apr 12;378(15):1408–1418.
³ Chi, Kim. et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2019; 10.1056/NEJMoa1903307.
⁴ Small, E. et al. SPARTAN, a phase 3 double-blind, randomized study of apalutamide (APA) vs placebo (PBO) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC). 2018 Genitourinary Cancers Symposium. Abstract #161.
⁵ Smith, M. et al. Apalutamide and Overall Survival in Patients with Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC): Updated Results from the Phase 3 SPARTAN Study. 2019 European Society for Medical Oncology. Abstract #843O.
⁶ Smith, M, et al. Apalutamide and Overall Survival in Patients with Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC): Updated Results from the Phase 3 SPARTAN Study. Ann Oncol. (2019) 30 (suppl_5): v325-v355. 10.1093/annonc/mdz248.
⁷ European Medicines Agency. ERLEADA. Available at: https://www.ema.europa.eu/en/documents/product-information/erleada-epar-product-information_en.pdf. Accessed May 2020.
⁸ Scher, HI. et al. Design and endpoints of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008;26:1148–1159. Accessed May 2020.
⁹ Scher, HI. et al. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016;34:1402–1418. Accessed May 2020.
¹⁰ Virgo, K. et al. Second-Line Hormonal Therapy for Men with Chemotherapy-Naïve, Castration-Resistant Prostate Cancer: American Society of Clinical Oncology Provisional Clinical Opinion. J Clin Oncol. 2017; 0732–183X/17/3599–1. Accessed May 2020.
¹¹ Saad, F., et al. The 2015 CUA0CUOG guidelines for the management of castration-resistant prostate cancer (CRPC). Can Urol Assoc J. 2015;9(3-4):90–96. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4455631/. Accessed May 2020.
¹² American Cancer Society. Cancer Facts & Figures. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf. Accessed May 2020.
¹³ ERLEADA product information Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210951s001lbl.pdf. Accessed May 2020.

May 2020
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