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Galeterone activity in castration-resistant prostate cancer
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The global pharmaceutical market will be worth US$1·3 trillion by 2018, an increase of 30% from 2013, according to a new report by IMS Health, an information, services, and technology company. Ageing populations will spur demand, while the advent of new specialty drugs will push up prices— the report predicted that 94% of the expected growth in the European pharmaceutical market will be attributable to such drugs. “In Europe, specialty medicines have emerged as the major growth driver as most new medicines now target niche populations with high unmet needs”, noted the authors. The oncology drug market was forecast to reach roughly $100 billion by 2018, up from $65 billion last year. “We would frame the increase in the context of a very strong pipeline of innovative
drugs that have recently come to market and will continue to come to market over the next 5 years”, explained IMS Health’s Murray Aitken. These drugs will include several new immunotherapies, including the PD-1 and CDK inhibitors. Indeed, the oncology drug pipeline is in exceptional shape, comprising 31% of the total pipeline and 25% of products in late-stage development. “At the same time, we have the rising incidence of cancer and we also have an expansion of access to cancer drugs by patients all over the world”, added Aitken. His organisation’s report also outlined the international availability of the 41 novel oncology drugs launched between 2008 and 2012. Patients in the USA had access to 31 of these drugs, patients in the UK had access to 24, and patients in Spain had access to only ten. How the expanding market will affect national health-care systems
is difficult to define. IMS Health believes that rebates and discounts will reduce the forecast growth by about 25%. So net growth to 2018 is likely to hover in the $220–250 billion region. Still, for straitened European economies, sharp increases in drugs costs will be difficult to accommodate. “We need to consider new ways to make access to effective drugs affordable for the NHS”, Cancer Research UK’s Emma Greenwood told The Lancet Oncology. The UK Government has announced a review of the country’s drug development process, from research to take up in the NHS. “It is also essential for industry and government to work together to manage the rising cost of cancer care”, concluded Greenwood.
Leonello Calvetti/Science Photo Library
Oncology drug market worth predicted to increase
Published Online November 28, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)71164-7
Talha Khan Burki
Galeterone activity in castration-resistant prostate cancer At the 2014 EORTC-NCI-AACR, MaryEllen Taplin and colleagues reported the findings of their phase 2 ARMOR2 study of an androgen receptor (AR) inhibitor galeterone (2250 mg once a day, orally) in patients with castrationresistant prostate cancer. Within 12 weeks of treat ment, 42 (82%) of 51 assessable patients with non-metastatic or metastatic treatment-naive castration-resistant prostate cancer had a 30% reduction in prostate-specific antigen (PSA) and 38 (75%) had a 50% reduction. Four (27%) of 15 assessable patients with abiraterone-refractory disease had reductions in PSA, including two (13%) with a 30% reduction. Preliminary results for patients with enzalutamiderefractory disease were not reported. The average numbers of circulating tumour cells after 1 week of treatment were 4·1 per mL in 15 patients with non-metastatic treatment-naive castration-resistant prostate cancer, www.thelancet.com/oncology Vol 16 January 2015
17·9 cells per mL in 29 with metastatic treatment-naive disease, and 21·1 cells per mL in 27 with abiraterone-refractory or enzalutamide-refractory disease. Six of 11 patients with non-metastatic or metastatic treatment-naive castration-resistant prostate cancer tested had high expression of N-terminal AR and loss of C-terminal AR. Five (83%) of these six patients had a 50% reduction in PSA in response to galeterone. 74% of patients had grade 1 or 2 treatmentrelated adverse events including increased aminotransferases, anorexia, diarrhoea, fatigue, nausea, and pruritus. The results of a recent trial by Emmanuel Antonarakis and colleagues “suggest that AR-V7 (an AR splice variant) confers resistance to both enzalutamide and abiraterone”, says Guru Sonpavde (UAB Comprehensive Cancer Center, Birmingham, AL, USA). “Galeterone combines the mechanisms of action of CYP17 inhibition and AR antagonism and degradation”, he
adds. According to Sonpavde, Taplin and colleagues’ most promising result was the 50% fall in PSA in most patients with AR C-terminal loss, “suggesting that galeterone has activity in patients with AR splice variants (eg, AR-V7). Indeed preclinical data suggest that galeterone lowers AR and AR-V7 protein levels and growth of AR-V7-expressing tumours”. Hence, Sonpavde adds, galeterone might “fulfil an unmet need in patients who either have AR-V7 at baseline or develop the variant after enzalutamide or abiraterone treatment”. A randomised phase 3 registration trial (ARMOR3-SV) for comparison of enzalutamide and galeterone is planned in patients with chemotherapy-naive, enzalutamide-naive, and abiraterone-naive metastatic castration-resistant prostate cancer and AR-V7 in circulating tumour cells.
Published Online November 28, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)71165-9 For the ARMOR2 study see http:// www.ecco-org.eu/Events/EORTC_ NCI_AACR_2014/SearchableProgramme#anchorScpr For the study by Antonarakis and colleagues see N Engl J Med 2014; 371: 1028–38
Farhat Yaqub e10
The global pharmaceutical market will be worth US$1·3 trillion by 2018, an increase of 30% from 2013, according to a new report by IMS Health, an information, services, and technology company. Ageing populations will spur demand, while the advent of new specialty drugs will push up prices— the report predicted that 94% of the expected growth in the European pharmaceutical market will be attributable to such drugs. “In Europe, specialty medicines have emerged as the major growth driver as most new medicines now target niche populations with high unmet needs”, noted the authors. The oncology drug market was forecast to reach roughly $100 billion by 2018, up from $65 billion last year. “We would frame the increase in the context of a very strong pipeline of innovative
drugs that have recently come to market and will continue to come to market over the next 5 years”, explained IMS Health’s Murray Aitken. These drugs will include several new immunotherapies, including the PD-1 and CDK inhibitors. Indeed, the oncology drug pipeline is in exceptional shape, comprising 31% of the total pipeline and 25% of products in late-stage development. “At the same time, we have the rising incidence of cancer and we also have an expansion of access to cancer drugs by patients all over the world”, added Aitken. His organisation’s report also outlined the international availability of the 41 novel oncology drugs launched between 2008 and 2012. Patients in the USA had access to 31 of these drugs, patients in the UK had access to 24, and patients in Spain had access to only ten. How the expanding market will affect national health-care systems
is difficult to define. IMS Health believes that rebates and discounts will reduce the forecast growth by about 25%. So net growth to 2018 is likely to hover in the $220–250 billion region. Still, for straitened European economies, sharp increases in drugs costs will be difficult to accommodate. “We need to consider new ways to make access to effective drugs affordable for the NHS”, Cancer Research UK’s Emma Greenwood told The Lancet Oncology. The UK Government has announced a review of the country’s drug development process, from research to take up in the NHS. “It is also essential for industry and government to work together to manage the rising cost of cancer care”, concluded Greenwood.
Leonello Calvetti/Science Photo Library
Oncology drug market worth predicted to increase
Published Online November 28, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)71164-7
Talha Khan Burki
Galeterone activity in castration-resistant prostate cancer At the 2014 EORTC-NCI-AACR, MaryEllen Taplin and colleagues reported the findings of their phase 2 ARMOR2 study of an androgen receptor (AR) inhibitor galeterone (2250 mg once a day, orally) in patients with castrationresistant prostate cancer. Within 12 weeks of treat ment, 42 (82%) of 51 assessable patients with non-metastatic or metastatic treatment-naive castration-resistant prostate cancer had a 30% reduction in prostate-specific antigen (PSA) and 38 (75%) had a 50% reduction. Four (27%) of 15 assessable patients with abiraterone-refractory disease had reductions in PSA, including two (13%) with a 30% reduction. Preliminary results for patients with enzalutamiderefractory disease were not reported. The average numbers of circulating tumour cells after 1 week of treatment were 4·1 per mL in 15 patients with non-metastatic treatment-naive castration-resistant prostate cancer, www.thelancet.com/oncology Vol 16 January 2015
17·9 cells per mL in 29 with metastatic treatment-naive disease, and 21·1 cells per mL in 27 with abiraterone-refractory or enzalutamide-refractory disease. Six of 11 patients with non-metastatic or metastatic treatment-naive castration-resistant prostate cancer tested had high expression of N-terminal AR and loss of C-terminal AR. Five (83%) of these six patients had a 50% reduction in PSA in response to galeterone. 74% of patients had grade 1 or 2 treatmentrelated adverse events including increased aminotransferases, anorexia, diarrhoea, fatigue, nausea, and pruritus. The results of a recent trial by Emmanuel Antonarakis and colleagues “suggest that AR-V7 (an AR splice variant) confers resistance to both enzalutamide and abiraterone”, says Guru Sonpavde (UAB Comprehensive Cancer Center, Birmingham, AL, USA). “Galeterone combines the mechanisms of action of CYP17 inhibition and AR antagonism and degradation”, he
adds. According to Sonpavde, Taplin and colleagues’ most promising result was the 50% fall in PSA in most patients with AR C-terminal loss, “suggesting that galeterone has activity in patients with AR splice variants (eg, AR-V7). Indeed preclinical data suggest that galeterone lowers AR and AR-V7 protein levels and growth of AR-V7-expressing tumours”. Hence, Sonpavde adds, galeterone might “fulfil an unmet need in patients who either have AR-V7 at baseline or develop the variant after enzalutamide or abiraterone treatment”. A randomised phase 3 registration trial (ARMOR3-SV) for comparison of enzalutamide and galeterone is planned in patients with chemotherapy-naive, enzalutamide-naive, and abiraterone-naive metastatic castration-resistant prostate cancer and AR-V7 in circulating tumour cells.
Published Online November 28, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)71165-9 For the ARMOR2 study see http:// www.ecco-org.eu/Events/EORTC_ NCI_AACR_2014/SearchableProgramme#anchorScpr For the study by Antonarakis and colleagues see N Engl J Med 2014; 371: 1028–38
Farhat Yaqub e10