Nubeqa® (darolutamide) dla pacjentow z non-mCRPC (FDA)
: 31 lip 2019, 11:36
About Nubeqa® (darolutamide)
Nubeqa® (darolutamide) is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription.1
Nubeqa is approved for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC).1
A Phase III study in metastatic hormone-sensitive prostate cancer (ARASENS) is ongoing. Information about this trial can be found at http://www.clinicaltrials.gov.
https://markets.businessinsider.com/new ... 1028400843
ASCO-GU 2019 – Bayer and Orion have their work cut out with darolutamide
February 14, 2019
When entering a prostate cancer market about to see the genericisation of Zytiga, Johnson & Johnson carved out a novel use – non-metastatic disease – for its follow-on drug Erleada.
This strategy was copied by Pfizer/Astellas’s Xtandi, and it could soon result in a third entry, darolutamide from Bayer and Orion.
However, results from darolutamide’s pivotal Aramis study, presented today at the Asco-Genitourinary Cancers symposium, show how hard it will be for the newcomers to compete. The efficacy data are virtually identical to those reported in Erleada and Xtandi’s respective Spartan and Prosper studies, meaning that the drugs’ safety profiles will be more important in determining their use.
Writing in today’s New England Journal of Medicine, where the Aramis data were simultaneously published, the trial’s investigators made much of darolutamide’s potential for lower toxicity. This, they argue, was due to the molecule’s distinct structure, which results in low blood/brain barrier penetration and low binding affinity for GABAA receptors.
On the question of efficacy, however, they accepted that: “The metastasis-free survival with darolutamide is similar to that in ... Prosper and Spartan.”
Tabel 1
Cross-trial efficacy comparisons in non-metastatic, castration-resistant prostate cancer
Among adverse events of note, the authors highlighted fatigue, asthenia (abnormal physical weakness), falls and fractures as less common in Aramis than in rival studies. Cross-trial comparisons are by definition unsound, but in the absence of head-to-head data they are all that prescribers will have to go on.
Also importantly, patients with a history of seizure were not allowed to enter the Spartan and Prosper studies – something that did not apply to Aramis, thanks to darolutamide’s lack of proconvulsive potential in animal trials.
In Aramis there were just two seizures on darolutamide and one in the control group.
Table 2
Cross-trial comparison of selected adverse events reported
A separate consideration, of course, is whether non-metastatic prostate cancer is a genuine setting for these types of drugs, or whether it is one that has been invented to get around the loss of patent protection for Zytiga, which is approved only in metastatic and hormone-sensitive settings.
Some might ask, for instance, whether patients can accurately be classified as non-metastatic or whether this is just a shortcoming of conventional imaging techniques, meaning that they might actually be metastatic and could be prescribed Zytiga according to this drug’s label.
The question is whether there is a window between patients becoming castration-resistant and developing metastases and, if so, how big this window might be. The Aramis authors argue that “delaying the development of metastases ... is a key therapeutic goal”.
It is also unclear how big a market this might amount to.
Erleada was approved a year ago, but J&J has not disclosed its sales and only says it is "pleased" with the drug’s launch progress.
Pfizer does not split out Xtandi sales by metastatic and non-metastatic disease, but on its fourth-quarter analyst call boasted: “In just six months our market share is quadruple that of Erleada.”
Darolutamide is expected to sell $819m in 2024, according to EvaluatePharma’s sellside consensus. Now that the Loxo-derived Vitrakvi has been launched darolutamide is Bayer’s biggest pipeline hope.
Even if Zytiga and its generic alternatives do not enter into the equation, Bayer and Orion will still have a hard task competing against the more established prostate cancer players, J&J and Pfizer/Astellas. Whether darolutamide can achieve forecast sales numbers will therefore depend on pricing and marketing muscle at least as much as on its safety profile.
https://www.evaluate.com/vantage/articl ... rk-cut-out
FDA Approves Bayer's Nubeqa® (darolutamide), a New Treatment for Men with Non-Metastatic Castration-Resistant Prostate Cancer
July 30, 2019
The U.S. Food and Drug Administration (FDA) today approved Nubeqa® (darolutamide), an androgen receptor inhibitor (ARi), for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC). The FDA approval is based on the Phase III ARAMIS trial evaluating Nubeqa plus androgen deprivation therapy (ADT), which demonstrated a highly significant improvement in the primary efficacy endpoint of metastasis-free survival (MFS), with a median of 40.4 months versus 18.4 months for placebo plus ADT (p<0.0001).
MFS is defined as the time from randomization to the time of first evidence of blinded independent central review (BICR)-confirmed distant metastasis or death from any cause within 33 weeks after the last evaluable scan, whichever occurred first.
Nubeqa was approved under the FDA’s Priority Review designation, which is reserved for medicines that may provide significant improvements in the safety or effectiveness of the treatment for serious conditions.
(…)
In the ARAMIS trial, both arms showed a 9 percent discontinuation rate due to adverse reactions.1
The most frequent adverse reactions requiring discontinuation in patients who received Nubeqa included cardiac failure (0.4 percent), and death (0.4 percent). Adverse reactions occurring more frequently in the Nubeqa arm (≥2 percent over placebo) were fatigue (16 percent versus 11 percent), pain in extremity (6 percent versus 3 percent) and rash (3 percent versus 1 percent).
Nubeqa was not studied in women and there is a warning and precaution for embryo-fetal toxicity.
Overall survival (OS) and time to pain progression were additional secondary efficacy endpoints.1 OS data were not yet mature at the time of final MFS analysis. The MFS result was supported by a delay in time to pain progression, defined as at least a 2-point worsening from baseline of the pain score on Brief Pain Inventory-Short Form or initiation of opioids, in patients treated with Nubeqa as compared to placebo. Pain progression was reported in 28 percent of all patients on study.
Bayer has filed for approval of Nubeqa in the European Union (EU), Japan, and with other health authorities. Nubeqa is developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company.
https://www.pcf.org/news/fda-approves-b ... 0190730fda
Bayer bags FDA nod for early prostate cancer drug darolutamide
http://www.pmlive.com/pharma_news/bayer ... de_1295937
Nubeqa® (darolutamide) is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription.1
Nubeqa is approved for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC).1
A Phase III study in metastatic hormone-sensitive prostate cancer (ARASENS) is ongoing. Information about this trial can be found at http://www.clinicaltrials.gov.
https://markets.businessinsider.com/new ... 1028400843
ASCO-GU 2019 – Bayer and Orion have their work cut out with darolutamide
February 14, 2019
When entering a prostate cancer market about to see the genericisation of Zytiga, Johnson & Johnson carved out a novel use – non-metastatic disease – for its follow-on drug Erleada.
This strategy was copied by Pfizer/Astellas’s Xtandi, and it could soon result in a third entry, darolutamide from Bayer and Orion.
However, results from darolutamide’s pivotal Aramis study, presented today at the Asco-Genitourinary Cancers symposium, show how hard it will be for the newcomers to compete. The efficacy data are virtually identical to those reported in Erleada and Xtandi’s respective Spartan and Prosper studies, meaning that the drugs’ safety profiles will be more important in determining their use.
Writing in today’s New England Journal of Medicine, where the Aramis data were simultaneously published, the trial’s investigators made much of darolutamide’s potential for lower toxicity. This, they argue, was due to the molecule’s distinct structure, which results in low blood/brain barrier penetration and low binding affinity for GABAA receptors.
On the question of efficacy, however, they accepted that: “The metastasis-free survival with darolutamide is similar to that in ... Prosper and Spartan.”
Tabel 1
Cross-trial efficacy comparisons in non-metastatic, castration-resistant prostate cancer
Among adverse events of note, the authors highlighted fatigue, asthenia (abnormal physical weakness), falls and fractures as less common in Aramis than in rival studies. Cross-trial comparisons are by definition unsound, but in the absence of head-to-head data they are all that prescribers will have to go on.
Also importantly, patients with a history of seizure were not allowed to enter the Spartan and Prosper studies – something that did not apply to Aramis, thanks to darolutamide’s lack of proconvulsive potential in animal trials.
In Aramis there were just two seizures on darolutamide and one in the control group.
Table 2
Cross-trial comparison of selected adverse events reported
A separate consideration, of course, is whether non-metastatic prostate cancer is a genuine setting for these types of drugs, or whether it is one that has been invented to get around the loss of patent protection for Zytiga, which is approved only in metastatic and hormone-sensitive settings.
Some might ask, for instance, whether patients can accurately be classified as non-metastatic or whether this is just a shortcoming of conventional imaging techniques, meaning that they might actually be metastatic and could be prescribed Zytiga according to this drug’s label.
The question is whether there is a window between patients becoming castration-resistant and developing metastases and, if so, how big this window might be. The Aramis authors argue that “delaying the development of metastases ... is a key therapeutic goal”.
It is also unclear how big a market this might amount to.
Erleada was approved a year ago, but J&J has not disclosed its sales and only says it is "pleased" with the drug’s launch progress.
Pfizer does not split out Xtandi sales by metastatic and non-metastatic disease, but on its fourth-quarter analyst call boasted: “In just six months our market share is quadruple that of Erleada.”
Darolutamide is expected to sell $819m in 2024, according to EvaluatePharma’s sellside consensus. Now that the Loxo-derived Vitrakvi has been launched darolutamide is Bayer’s biggest pipeline hope.
Even if Zytiga and its generic alternatives do not enter into the equation, Bayer and Orion will still have a hard task competing against the more established prostate cancer players, J&J and Pfizer/Astellas. Whether darolutamide can achieve forecast sales numbers will therefore depend on pricing and marketing muscle at least as much as on its safety profile.
https://www.evaluate.com/vantage/articl ... rk-cut-out
FDA Approves Bayer's Nubeqa® (darolutamide), a New Treatment for Men with Non-Metastatic Castration-Resistant Prostate Cancer
July 30, 2019
The U.S. Food and Drug Administration (FDA) today approved Nubeqa® (darolutamide), an androgen receptor inhibitor (ARi), for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC). The FDA approval is based on the Phase III ARAMIS trial evaluating Nubeqa plus androgen deprivation therapy (ADT), which demonstrated a highly significant improvement in the primary efficacy endpoint of metastasis-free survival (MFS), with a median of 40.4 months versus 18.4 months for placebo plus ADT (p<0.0001).
MFS is defined as the time from randomization to the time of first evidence of blinded independent central review (BICR)-confirmed distant metastasis or death from any cause within 33 weeks after the last evaluable scan, whichever occurred first.
Nubeqa was approved under the FDA’s Priority Review designation, which is reserved for medicines that may provide significant improvements in the safety or effectiveness of the treatment for serious conditions.
(…)
In the ARAMIS trial, both arms showed a 9 percent discontinuation rate due to adverse reactions.1
The most frequent adverse reactions requiring discontinuation in patients who received Nubeqa included cardiac failure (0.4 percent), and death (0.4 percent). Adverse reactions occurring more frequently in the Nubeqa arm (≥2 percent over placebo) were fatigue (16 percent versus 11 percent), pain in extremity (6 percent versus 3 percent) and rash (3 percent versus 1 percent).
Nubeqa was not studied in women and there is a warning and precaution for embryo-fetal toxicity.
Overall survival (OS) and time to pain progression were additional secondary efficacy endpoints.1 OS data were not yet mature at the time of final MFS analysis. The MFS result was supported by a delay in time to pain progression, defined as at least a 2-point worsening from baseline of the pain score on Brief Pain Inventory-Short Form or initiation of opioids, in patients treated with Nubeqa as compared to placebo. Pain progression was reported in 28 percent of all patients on study.
Bayer has filed for approval of Nubeqa in the European Union (EU), Japan, and with other health authorities. Nubeqa is developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company.
https://www.pcf.org/news/fda-approves-b ... 0190730fda
Bayer bags FDA nod for early prostate cancer drug darolutamide
http://www.pmlive.com/pharma_news/bayer ... de_1295937