Roche’s IPATential150 study evaluating ipatasertib in combination with abiraterone and prednisone/prednisolone met one of its co-primary endpoints
·Phase III IPATential150 study evaluating ipatasertib in combination with abiraterone and prednisone/prednisolone compared to current standard-of-care (abiraterone and prednisone/prednisolone alone) plus placebo met its co-primary endpoint of radiographic progression free survival (rPFS) in patients with PTEN loss tumours
Basel, 19 June 2020 – Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the phase III IPATential150 study met its co-primary endpoint of radiographic progression-free survival (rPFS) in patients with metastatic castration-resistant prostate cancer (mCRPC) and whose tumours had PTEN loss. In this patient group, ipatasertib in combination with abiraterone and prednisone/prednisolone provided a statistically significant reduction in the risk of disease worsening or death, compared to current standard of care (abiraterone and prednisone/prednisolone) plus placebo. The other co-primary endpoint of rPFS in the overall study population (ITT) was not met. The safety profile for the combination of ipatasertib and abiraterone was consistent with previous analyses and known risks. The results of the IPATential150 study will be presented at an upcoming medical meeting.
While initial data are encouraging, overall survival benefit and additional secondary endpoints are not yet mature. The trial will continue until the next planned analysis and data will be shared with health authorities.
“Prostate cancer remains a leading cause of death in men worldwide and patients with metastatic castration-resistant prostate cancer can be difficult to treat,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “The early results of the IPATential150 study are encouraging in our ongoing mission to develop new treatment options for people with advanced prostate cancer.”
Ipatasertib is an oral, highly specific, investigational medicine designed to target and bind to all three isoforms of AKT (protein kinase B), which blocks the PI3K/AKT signalling pathway – a key driver of cancer cell growth and proliferation in prostate cancer.1,2 The PI3K/AKT pathway has also been implicated in resistance to anti-androgen therapy as androgen receptor (AR) inhibition is associated with an increase in AKT pathway activation.2,3 Functional loss of the tumour suppressor protein PTEN within the tumour, seen in approximately 40-60% of mCRPC patients, results in hyperactivation of the PI3K/AKT pathway and is associated with adverse outcomes such as increased tumour grade and stage, earlier biochemical recurrence after radical prostatectomy, metastasis, prostate-cancer-specific death, and androgen-independent progression.4,5
Roche’s clinical development programme for ipatasertib focuses on tumours that are frequently found to have activation of the PI3K/AKT pathway. In addition to prostate cancer, ipatasertib is being studied in certain types of breast cancer including triple-negative breast cancer (TNBC) and hormone-receptor positive (HR+), HER2- negative breast cancer. Results are anticipated later in 2020.
About the IPATential150 study6
IPATential150 is a double-blind, placebo-controlled, randomised phase III study assessing ipatasertib in combination with abiraterone and prednisone/prednisolone, compared to placebo plus abiraterone and prednisone/prednisolone, in adult male patients with asymptomatic or mildly symptomatic, previously untreated mCRPC.
The co-primary endpoints of the study are investigator-determined rPFS in the overall study population, as well as a subpopulation whose tumours have PTEN loss, as assessed by immunohistochemistry (Ventana assay). PFS in the study is defined as the time from date of randomisation to the first occurrence of disease progression or death from any cause, whichever occurs earlier. Secondary endpoints include overall survival, safety, time to pain progression, time to initiation of cytotoxic chemotherapy and time to function deterioration.
Ipatasertib is an oral, highly specific, investigational medicine designed to target and bind to all three isoforms of AKT, which blocks the PI3K/AKT signalling pathway and may prevent cancer cell growth and survival.1,2
Ipatasertib is being studied in tumours that are frequently found to have activation of the PI3K/AKT pathway, including breast and prostate cancers. Clinical studies are ongoing to evaluate the efficacy and safety of ipatasertib and the opportunity it may provide to address significant unmet needs for patients with these diseases.
Ipatasertib was discovered at Genentech in partnership with Array BioPharma Inc. (acquired by Pfizer Inc. on July 30, 2019).
About metastatic castration-resistant prostate cancer (mCRPC)
Prostate cancer is the second most frequent cancer and the fifth leading cause of death in men.7 Metastatic prostate cancer refers to prostate cancer that has spread beyond the prostate to other parts of the body (metastasised).8 Although most men are cured with treatment of localised disease, recurrent or newly diagnosed metastatic disease is associated with significant morbidity and mortality.9,10,11
Primary treatment of advanced prostate cancer is androgen deprivation therapy (ADT); however, up to one-third of patients will progress despite reduction in serum testosterone levels to castrate levels (<50 ng/dL), either through surgical or medical castration.12,13 Castration-resistant prostate cancer (CRPC) is defined by disease progression, as measured by prostate specific antigen (PSA) or radiographic measures, despite adequate suppression of serum testosterone levels.14,15 Despite the current availability of life-extending therapies for mCRPC, the majority of men will die of their disease: the median life expectancy in this population is less than three years.16,17
Prostate cancer growth and survival is driven by abnormal AR signalling. In CRPC, cell growth and proliferation is also commonly driven by activation of the PI3K/AKT signalling pathway.1,2 In particular, functional loss of the tumour suppressor protein PTEN within the tumour, seen in approximately 40-60% of people with mCRPC, results in hyperactivation of the PI3K/AKT pathway.4 PTEN loss is associated with adverse outcomes such as increased tumour grade and stage, earlier biochemical recurrence after radical prostatectomy, metastasis, prostate-cancer-specific death, and androgen-independent progression.5 The PI3K/AKT pathway has also been implicated in resistance to anti-androgen therapy as AR inhibition is associated with an increase in AKT pathway activation, suggesting that the tumour compensates for the loss of one pathway with another.2,3
About Roche in prostate cancer
For more than 50 years, Roche has been developing medicines with the goal of redefining treatment in oncology. Our research and development aim is to provide effective cancer therapies through the discovery and development of novel therapeutics that target the specific molecular pathways associated with cancer. Roche is expanding into additional areas of unmet need, working to find innovative solutions for diseases such as prostate cancer, the most prevalent cancer in men and fifth leading cause of cancer-related male death worldwide.5 Roche is committed to research into genitourinary cancers, including bladder and renal cancers, and to providing life extending treatment options for these patients.
Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare – a strategy that aims to fit the right treatment to each patient in the best way possible.
Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.
Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. More than thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the eleventh consecutive year, Roche has been recognised as one of the most sustainable companies in the Pharmaceuticals Industry by the Dow Jones Sustainability Indices (DJSI).
The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2019 employed about 98,000 people worldwide. In 2019, Roche invested CHF 11.7 billion in R&D and posted sales of CHF 61.5 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.
All trademarks used or mentioned in this release are protected by law.
 Yang J, et al. Targeting PI3K in cancer: mechanisms and advances in clinical trials. Mol Cancer. 2019; 18(1).
 Crumbaker M, et al. AR Signaling and the PI3K pathway in prostate cancer. Cancers (Basel). 2017; 9(4):34.
 Wang Y, et al. Cross-talk between the androgen receptor and the phosphatidylinositol 3-kinase/AKT pathway in prostate cancer. Current Cancer Drug Targets. 2007; 7(6), 591-604.
 De Bono JS, et al. Randomized phase ii study evaluating AKT blockade with ipatasertib, in combination with abiraterone, in patients with metastatic prostate cancer with and without PTEN loss. Clin Cancer Res. 2019; 25(3);928-36.
 Jamaspishvili T, et al. Clinical implications of PTEN loss in prostate cancer. Nat Rev Urol. 2018; 15(4):222-34.
 Clinical trials.gov. Ipatasertib plus abiraterone plus prednisone/prednisolone, relative to placebo plus abiraterone plus prednisone/prednisolone in adult male patients with metastatic castrate-resistant prostate cancer (IPATential150). [Internet; cited June 2020]. Available from: https://clinicaltrials.gov/ct2/show/record/NCT03072238?term=ipatential150&draw=2&rank=1
 Bray F, et al. Global cancer statistics 2018: GLOBOCAN Estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin. 2018; 68:394-424.
 Cancer.net. Treatment of metastatic castration-resistant prostate cancer. [Internet; cited June 2020]. Available from: www.cancer.net/research-and-advocacy/asco-care-and-treatment-recommendations-patients/treatment-metastatic-castration-resistant-prostate-cancer.
 Johansson JE, et al. Natural History of Early, Localized Prostate Cancer. JAMA. 2004;291(22):2713-2719.
 Lee R, et al. Treatment and prevention of bone complications from prostate cancer. Bone. 2011; 48 (1): 88-95.
 Soest R et al. The Natural History and Outcome Predictors of Metastatic Castration-resistant Prostate Cancer. European Urology Focus. 2016; 2 (5): 480-487.
 Petrovich Z, et al. Adenocarcinoma of the prostate: innovations in management. Am J Clin Oncol. 1997;20:111-9.
 Petrylak DP. Current state of castration-resistant prostate cancer. Am J Manag Care. 2013;19(18 Suppl):s358‐s365.
 Kirby M, et al. Characterising the castration-resistant prostate cancer population: a systematic review. International Journal of Clinical Practice, 2011;65(11);1180–92.
 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(12):1402–1418.
 Ryan CJ, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy N. Engl. J. Med. 2013; 368(368):138–148. doi: 10.1056/NEJMoa1209096.
 Beer TM, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N. Engl. J. Med. 2014; 371:424–433. doi: 10.1056/NEJMoa1405095.
Roche Group Media Relations
Phone: +41 61 688 8888 / e-mail: firstname.lastname@example.org
- Nicolas Dunant (Head)
- Patrick Barth
- Daniel Grotzky
- Karsten Kleine
- Nathalie Meetz
- Barbara von Schnurbein
One Liberty Plaza - 165 Broadway
NY 10006 New York
GlobeNewswire is one of the world's largest newswire distribution networks, specializing in the delivery of corporate press releases financial disclosures and multimedia content to the media, investment community, individual investors and the general public.
Subscribe to releases from GlobeNewswire
Subscribe to all the latest releases from GlobeNewswire by registering your e-mail address below. You can unsubscribe at any time.
Latest releases from GlobeNewswire
Galapagos increases share capital through subscription right exercises18.9.2020 22:01:00 CEST | Press release
Mechelen, Belgium; 18 September 2020, 22.01 CET; regulated information – Galapagos NV (Euronext & NASDAQ: GLPG) announces a share capital increase arising from subscription right exercises. Galapagos issued 86,280 new ordinary shares on 18 September 2020, for a total capital increase (including issuance premium) of €2,403,087. Pursuant to the subscription right exercise program of Galapagos’ management board, members of the management board automatically are committed to exercise a minimum number of subscription rights, subject to certain conditions. In accordance with the rules of this program, CEO Onno van de Stolpe exercised 15,000 subscription rights. Three other management board members exercised an aggregate number of 15,000 subscription rights. In accordance with Belgian transparency legislation1, Galapagos notes that its total share capital currently amounts to €353,435,739.72, the total number of securities conferring voting rights amounts to 65,340,842, which is also the tota
CONDITIONS FOR RIKSBANK REVERSED AUCTIONS SEK GOVERNMENT BONDS18.9.2020 16:20:00 CEST | Press release
Sveriges Riksbank Bid procedure details Government Bonds, 2020-09-25 Maturity dateLoanISIN codeCouponVolume, SEK million2029-11-121061 SE00112819220.75 %1,000 +/- 2502032-06-01 1056 SE00045172902.25 %1,000 +/- 250 Settlement date 2020-09-29 Bids have to be entered by 10.00 on SEP 25, 2020 Highest permitted bid volume: 1 000 million in issue SGB 1061 and 1 000 SEK million in issue SGB 1056 Lowest permitted bid volume: 50 SEK million Bids only through counterparties approved by the Riksbank RESULT OF AUCTION WILL BE PUBLISHED NO LATER THAN 10.10 (CEST)ON SEP 25, 2020. For more information, please contact: Trading desk at the Riksbank + 46 8 696 6970 General and special terms and conditions can be retrieved at http://www.riksbank.se
CONDITIONS FOR RIKSBANK REVERSED AUCTIONS SEK COVERED BONDS18.9.2020 16:20:00 CEST | Press release
Sveriges Riksbank Bid procedure details Covered Bonds, 2020-09-24 Maturity dateLoanISIN codeCouponVolume, SEK million2022-04-08 5531 SE00069912461.00 %1,000 +/- 5002022-12-21 575 SE00105465721.50 %1,000 +/- 500 2022-09-211586SE00031748384.50 %1,000 +/- 5002022-06-15191SE00075256541.00 %1,000 +/- 5002022-12-212212SE00102970851.00 %400 +/- 2502022-09-21515SE00072784292.25 %400 +/- 2502022-06-15143SE00085866551.25 %400 +/- 250 Settlement date 2020-09-28 Bids have to be entered by 10.00 on SEP 24, 2020 Highest permitted bid volume: 1,000 SEK million in issue 5531 1,000 SEK million in issue 575 1,000 SEK million in issue 1586 1,000 SEK million in issue 191 400 SEK million in issue 2212 400 SEK million in issue 515 400 SEK million in issue 143 Maximum volume 5 billion SEK in total Lowest permitted bid volume: 50 SEK million Bids only through counterparties approved by the Riksbank RESULT OF AUCTION WILL BE PUBLISHED NO LATER THAN 10.15 (CEST) ON SEP 24, 2020. For more information, please con
CONDITIONS FOR RIKSBANK REVERSED AUCTIONS SEK MUNICIPAL BONDS18.9.2020 16:20:00 CEST | Press release
Sveriges Riksbank CONDITIONS FOR RIKSBANK REVERSED AUCTIONS SEK MUNICIPAL BONDS Bid procedure on 22 September 2020, Municipalities and Regions Bonds: Floating-Rate Notes (FRN) issued in SEK by Municipalities or Regions with maturity in 2025. The following issuers are accepted for delivery: Göteborgs KommunJönköpings KommunMalmö KommunNorrköpings Kommun Skåne Läns LandstingStockholms KommunSundsvalls KommunTäby KommunUppsala KommunVästerås KommunÖrebro KommunÖstersunds Kommun Delivery may not be made in Bonds purchased by the Counterparty from the issuer less than one week prior to the date for announcing the Specific terms, i.e. the purchase may not have been made after 11 September 2020. Bids: Bids are made to tel 08-696 69 70 and confirmed in writing by a filled-in Bid form by e-mail to EOL@riksbank.se. Bid date: Tuesday 22 September 2020 Bid time: 1000-1100 hours (CEST) on the Bid date Requested volume: (corresponding nominal amount) SEK 750 +/- 750 million Highest permitted bid vol
Karolinska Development’s portfolio company OssDsign strengthens patent coverage for OssDsign Cranial PSI in key market18.9.2020 16:04:55 CEST | Press release
STOCKHOLM, SWEDEN – September 18, 2020. Karolinska Development (Nasdaq Stockholm: KDEV) announces that its portfolio company OssDsign has received a notice of allowance from the United States Patent and Trademarks Office (USPTO) concerning the implant design for the company’s product Cranial PSI, thus strengthening the patent protection for the technology in the company’s most important market in the US. The patent covers the implant, its support structure, as well as the method of making customized implants for each patient. Approvals of the patent were given in the European and Japanese markets last year and in Australia earlier in 2020. With the allowance in the US, a stronger patent protection for OssDsign Cranial PSI is thus established in all key markets. The patent family is valid until 2035 and builds upon a broad international patent portfolio. “The notice of allowance granted by the USPTO is an important final step in securing the patent protection for the technology behind O
Karolinska Developments portföljbolag OssDsign stärker patentskyddet på huvudmarknad för OssDsign Cranial PSI18.9.2020 16:04:55 CEST | Pressemelding
STOCKHOLM, SVERIGE 18 september 2020. Karolinska Development AB (Nasdaq Stockholm: KDEV) meddelar idag att portföljbolaget OssDsign har givits ett godkännande av det amerikanska patentverket (USPTO) för ett patent relaterat till designen av bolagets produkt Cranial PSI. Genom godkännandet stärks patentskyddet för sin teknologi på bolagets viktigaste marknad USA. Patentet täcker implantatet, dess förstärkande struktur, samt metoden att tillverka ett patientspecifikt implantat. Bolaget erhöll patentskydd för produkten i Europa och Japan under föregående år och i Australien under början av 2020. Med godkännandet från den amerikanska myndigheten har nu bolaget etablerat ett starkt patentskydd för Cranial PSI på samtliga nyckelmarknader. Patentfamiljen, som är giltig till 2035, förstärker OssDsigns redan omfattande internationella patentskydd. ”Godkännandet från USPTO är ett viktigt sista steg för att säkerställa ett patentskydd för teknologin bakom OssDsigns Cranial PSI på alla viktiga mar