The past week has seen a mixture of positive and negative developments in Europe and the UK for chronic lymphocytic leukaemia (CLL), hepatocellular carcinoma (HCC) and non-small cell lung cancer (NSCLC).
Of particular interest, the UK's National Institute for Health and Clinical Excellence (NICE) has issued a recommendation for the use of Roche's MabThera (rituximab) in CLL. NICE's final guidance recommends rituximab in combination with fludarabine and cyclophosphamide chemotherapy (CT) as an option for previously-untreated patients with CLL. Professor John Gribben, Consultant Haematologist and Medical Oncologist, Barts and The London NHS Trust, commented: "the ability to add rituximab to chemotherapy is a major advance in the way we can treat CLL. Where previously our goal was just to improve symptoms, for the first time we now have a treatment combination that is capable of producing much higher remission rates and more durable responses."
Further, the EMEA's CHMP has issued a positive recommendation for the use of MabThera in patients with relapsed or refractory CLL. Physicians will soon be able to prescribe MabThera in combination with CT to patients in Europe who have been treated for the disease, but whose cancer has returned or have not appropriately responded to therapy.
Separately, the anticipated decision from NICE on the Final Appraisal Determination for Bayer HealthCare/Onyx Pharmaceuticals' Nexavar (sorafenib), for the treatment of advanced HCC, has been delayed to allow consideration of the patient access scheme, Bayer Schering Pharma has agreed with the Department of Health. The company hopes that NICE will take this opportunity to evaluate and fully understand the benefit of its proposed patient access scheme, and to listen to leading healthcare professionals in the field who were unanimous in their condemnation of the initial negative proposal.
Finally, the CHMP has adopted a negative opinion for the use of Erbitux (cetuximab) in combination with platinum-based CT for the treatment of patients with EGFr-expressing, advanced or metastatic NSCLC. Merck KGaA is evaluating potential appeal options requesting that the CHMP re-examines data demonstrating clinically-relevant benefits to patients. This has come as a huge blow to Merck, with its shares plummeting 12 per cent following the decision.
Alice Rossiter - Cancer Drug News Editor
Tuesday, July 28, 2009
Tuesday, July 21, 2009
Progress made in identifying genetic causes of melanoma
Researchers have identified various genes that cause melanoma and also novel epigenetic markers of the disease that may herald new treatments for patients.
Two studies, published online in Nature Genetics (10.1038/ng.410 and 10.1038/ng.411), and conducted by investigators at Queensland Institute of Medical Research in Australia, King's College London and the University of Leeds, have revealed novel genes implicated in the development of melanoma. One study found that specific changes in two genes, MTAP and PLA2G6, were found to make people more susceptible to developing nevi. In a further 4,000 people, the researchers went on to show that these genes increased the risk of developing melanoma; specifically, those who carry one of the two SNPs have a 25 per cent increased chance of developing melanoma, while for individuals carrying both variants, the risk is doubled.
The second study identified five loci with genotyped or imputed SNPs reaching very high significance. The analysis showed that the genes, MC1R and TYR, are associated with pigmentation, freckling and cutaneous sun sensitivity.
Separately, researchers from Yale University have mapped chemical modifications of DNA in the melanoma genome, finding new markers that will help to develop more effective treatment strategies to fight this disease. In this work, published online in Genome Research (10.1101/gr.091447.109), scientists found 76 promoters with altered methylation patterns in melanomas, most of these showing increased methylation compared to normal. The team focused on five genes in particular, three of which had not been implicated in melanoma until now. The scientists are hopeful that these epigenetic markers may provide a better method for determining the aggressiveness of the disease and for setting a course of treatment.
The incidence of melanoma has been increasing over the past decades. Currently, approximately 132,000 melanoma skin cancers occur globally each year and around 48,000 people worldwide die of melanoma annually. One in every three cancers diagnosed is a skin cancer and, according to Skin Cancer Foundation Statistics, one in every five Americans will develop skin cancer in their lifetime. Melanoma is diagnosed in more than 50,000 new patients in the US annually.
While the rate of incidences continues to rise, survival rate has not improved and the race is on to find the genetic and cellular changes driving melanoma and to devise new means of detection and treatment.
Alice Rossiter - Cancer Drug News Editor
Two studies, published online in Nature Genetics (10.1038/ng.410 and 10.1038/ng.411), and conducted by investigators at Queensland Institute of Medical Research in Australia, King's College London and the University of Leeds, have revealed novel genes implicated in the development of melanoma. One study found that specific changes in two genes, MTAP and PLA2G6, were found to make people more susceptible to developing nevi. In a further 4,000 people, the researchers went on to show that these genes increased the risk of developing melanoma; specifically, those who carry one of the two SNPs have a 25 per cent increased chance of developing melanoma, while for individuals carrying both variants, the risk is doubled.
The second study identified five loci with genotyped or imputed SNPs reaching very high significance. The analysis showed that the genes, MC1R and TYR, are associated with pigmentation, freckling and cutaneous sun sensitivity.
Separately, researchers from Yale University have mapped chemical modifications of DNA in the melanoma genome, finding new markers that will help to develop more effective treatment strategies to fight this disease. In this work, published online in Genome Research (10.1101/gr.091447.109), scientists found 76 promoters with altered methylation patterns in melanomas, most of these showing increased methylation compared to normal. The team focused on five genes in particular, three of which had not been implicated in melanoma until now. The scientists are hopeful that these epigenetic markers may provide a better method for determining the aggressiveness of the disease and for setting a course of treatment.
The incidence of melanoma has been increasing over the past decades. Currently, approximately 132,000 melanoma skin cancers occur globally each year and around 48,000 people worldwide die of melanoma annually. One in every three cancers diagnosed is a skin cancer and, according to Skin Cancer Foundation Statistics, one in every five Americans will develop skin cancer in their lifetime. Melanoma is diagnosed in more than 50,000 new patients in the US annually.
While the rate of incidences continues to rise, survival rate has not improved and the race is on to find the genetic and cellular changes driving melanoma and to devise new means of detection and treatment.
Alice Rossiter - Cancer Drug News Editor
Thursday, July 2, 2009
CSCs set to improve cancer treatment
Research into cancer treatment is currently focusing on cancer stem cells (CSCs), which are responsible for some instances of the disease. Indeed, a University of Rochester Medical Center researcher has resolved the controversy and promise around a dangerous subtype of CSCs, which seem capable of resisting many modern treatments. The research, published in the 26th June edition of Science (2009;324:1670-1673), proposes that this subpopulation of malignant cells may one day provide an important avenue for controlling cancer, especially if new treatments that target the CSC are developed and combined with traditional chemotherapy and/or radiation.
Research from the past ten years suggests that because CSCs may be the root of cancer, they might also provide a new opportunity for a treatment. A group of collaborators, for example, are testing a new drug compound based on the feverfew plant that demonstrates great potential in the laboratory for causing leukaemia CSCs to self destruct.
Further, it was recently reported that researchers at the University of California, Los Angeles Jonsson Comprehensive Cancer Center, on a quest to find lung cancer (LC) SCs, have developed a unique model to allow further investigation into the cells that many believe may be at the root of all LCs. Since CSCs are known to possess unique properties and a predisposition to metastasise, the study's lead author proposed to extract candidate CSCs directly from clinical specimens based on the markers they express and then validate these cells functionally. As detailed in PLoS ONE (10.1371/journal.pone.0005884), in an effort to find LC SCs, the team collected specimens from patients with malignant pleural effusions, and created a microenvironment in which the tumour cells would remain heterogeneous and enable researchers to more easily identify candidate CSCs.
Separately, a study from the University of Michigan (UM) Comprehensive Cancer Center recently indicated that a gene well known to stop or suppress cancer plays a role in CSCs. The researchers found that several pathways linked to the gene, PTEN, also affected the growth of breast cancer SCs. Further, by using a drug that interferes with that pathway, the scientists produced an up to 90 per cent decrease in the number of CSCs within a tumour. As detailed in PLoS Biology (10.1371/journal.pbio.1000121), the UM researchers deleted PTEN in tumours grown in cell cultures and mice, and found an increase in the number of SCs. They also looked at pathways associated with PTEN and reported that the pathway, PI3-K/Akt, regulated the CSC population by activating another SC pathway, Wnt, which is also implicated in multiple cancer types. Thus, new and recent developments seem to reiterate the important role of CSC research in future treatment.
Alice Rossiter
Cancer Drug News - Editor
Research from the past ten years suggests that because CSCs may be the root of cancer, they might also provide a new opportunity for a treatment. A group of collaborators, for example, are testing a new drug compound based on the feverfew plant that demonstrates great potential in the laboratory for causing leukaemia CSCs to self destruct.
Further, it was recently reported that researchers at the University of California, Los Angeles Jonsson Comprehensive Cancer Center, on a quest to find lung cancer (LC) SCs, have developed a unique model to allow further investigation into the cells that many believe may be at the root of all LCs. Since CSCs are known to possess unique properties and a predisposition to metastasise, the study's lead author proposed to extract candidate CSCs directly from clinical specimens based on the markers they express and then validate these cells functionally. As detailed in PLoS ONE (10.1371/journal.pone.0005884), in an effort to find LC SCs, the team collected specimens from patients with malignant pleural effusions, and created a microenvironment in which the tumour cells would remain heterogeneous and enable researchers to more easily identify candidate CSCs.
Separately, a study from the University of Michigan (UM) Comprehensive Cancer Center recently indicated that a gene well known to stop or suppress cancer plays a role in CSCs. The researchers found that several pathways linked to the gene, PTEN, also affected the growth of breast cancer SCs. Further, by using a drug that interferes with that pathway, the scientists produced an up to 90 per cent decrease in the number of CSCs within a tumour. As detailed in PLoS Biology (10.1371/journal.pbio.1000121), the UM researchers deleted PTEN in tumours grown in cell cultures and mice, and found an increase in the number of SCs. They also looked at pathways associated with PTEN and reported that the pathway, PI3-K/Akt, regulated the CSC population by activating another SC pathway, Wnt, which is also implicated in multiple cancer types. Thus, new and recent developments seem to reiterate the important role of CSC research in future treatment.
Alice Rossiter
Cancer Drug News - Editor
Wednesday, June 24, 2009
CRC rates on the rise
The incidence of colorectal cancer (CRC) is increasing in many countries around the world, according to a new study by the American Cancer Society. The study's authors believe the rise is due to the uptake of so-called 'western' diets and lifestyles, such as high red meat consumption and low levels of exercise. Previous studies have documented significant variations in CRC incidence rates and trends, regionally and across countries. However, no study has examined the worldwide pattern using the most recently updated incidence data from the International Agency for Research on Cancer (IARC).
Scientists reviewed data from 51 cancer registries around the world using databases created by the IARC in order to analyse rates of CRC from 1983 to 1987 through to 1998 to 2002. They found that CRC incidence rates statistically significantly increased for both men and women in 27 of the 51 cancer registries, although the increases were more prominent among men. Of particular note were Slovakia, Slovenia and the Czech Republic in the EU, and Japan, Kuwait and Israel in Asia. In Slovenia, CRC incidence increased by 70 per cent among men and 28 per cent among women, and in Miyagi, Japan, rates in men and women rose by 92 and 47 per cent, respectively.
The researchers, whose findings are published in the June edition of Cancer Epidemiology Biomarkers and Prevention (CEBP; 2009;18:1688-1694), also found that there were substantial variations in CRC incidences between different regional and ethnic groups in some countries, including Japan, Israel and Singapore. The only country where CRC rates statistically significantly declined in both sexes was the US, but the US had a very high rate of CRC to start with. In contrast, economically transitioning countries, such as eastern European nations, most parts of Asia and some South American countries, saw large rises in CRC rates. The study authors believe that this may reflect the increasing adoption of western lifestyles and behaviours in these countries.
Further, a separate study, also published in the same edition of CEBP (2009;18:1695-1698), has focused on the CRC incidence rates among young men and women in the US. The recent, accelerated decline in CRC incidence rates has largely been attributed to an increase in screening among adults aged 50 years and older. Scientists used data to report on CRC incidence trends from 1992 through 2005 among adults under the age of 50 years, for whom screening is not recommended for persons at average risk, by sex, race/ethnicity, age, stage at diagnosis and anatomic subsite.
Overall, incidence rates of CRC per 100,000 young individuals (ages 20 to 49 years) increased 1.5 and 1.6 per cent per year in men and women, respectively, from 1992 to 2005. Among non-Hispanic whites, rates increased for both men and women in each ten-year age grouping (20 to 29, 30 to 39 and 40 to 49 years) and for every stage of diagnosis. In contrast to the overall decreasing trend in CRC incidence in the US, rates are increasing among men and women under the age of 50 years. Further studies are necessary to elucidate causes for this trend, and identify potential prevention and early detection strategies.
Alice Rossiter - Cancer Drug News Editor
Scientists reviewed data from 51 cancer registries around the world using databases created by the IARC in order to analyse rates of CRC from 1983 to 1987 through to 1998 to 2002. They found that CRC incidence rates statistically significantly increased for both men and women in 27 of the 51 cancer registries, although the increases were more prominent among men. Of particular note were Slovakia, Slovenia and the Czech Republic in the EU, and Japan, Kuwait and Israel in Asia. In Slovenia, CRC incidence increased by 70 per cent among men and 28 per cent among women, and in Miyagi, Japan, rates in men and women rose by 92 and 47 per cent, respectively.
The researchers, whose findings are published in the June edition of Cancer Epidemiology Biomarkers and Prevention (CEBP; 2009;18:1688-1694), also found that there were substantial variations in CRC incidences between different regional and ethnic groups in some countries, including Japan, Israel and Singapore. The only country where CRC rates statistically significantly declined in both sexes was the US, but the US had a very high rate of CRC to start with. In contrast, economically transitioning countries, such as eastern European nations, most parts of Asia and some South American countries, saw large rises in CRC rates. The study authors believe that this may reflect the increasing adoption of western lifestyles and behaviours in these countries.
Further, a separate study, also published in the same edition of CEBP (2009;18:1695-1698), has focused on the CRC incidence rates among young men and women in the US. The recent, accelerated decline in CRC incidence rates has largely been attributed to an increase in screening among adults aged 50 years and older. Scientists used data to report on CRC incidence trends from 1992 through 2005 among adults under the age of 50 years, for whom screening is not recommended for persons at average risk, by sex, race/ethnicity, age, stage at diagnosis and anatomic subsite.
Overall, incidence rates of CRC per 100,000 young individuals (ages 20 to 49 years) increased 1.5 and 1.6 per cent per year in men and women, respectively, from 1992 to 2005. Among non-Hispanic whites, rates increased for both men and women in each ten-year age grouping (20 to 29, 30 to 39 and 40 to 49 years) and for every stage of diagnosis. In contrast to the overall decreasing trend in CRC incidence in the US, rates are increasing among men and women under the age of 50 years. Further studies are necessary to elucidate causes for this trend, and identify potential prevention and early detection strategies.
Alice Rossiter - Cancer Drug News Editor
Friday, June 19, 2009
J&J reveals two new compounds during R&D review
With an estimated 75 million cancer sufferers in the world by 2030 and the slow pace of drug development, Johnson & Johnson has recently reviewed its growth strategies and research and development pipeline in oncology with the aim of becoming a leader in cancer therapy within the next five years. The company is continuing to advance its pipeline of new compounds, while also exploring line extensions for existing drugs to fuel its long-term growth and address unmet medical needs in cancer.
Promising compounds in early development include CNTO 328, an anti-interleukin-6 monoclonal antibody, and CNTO 888, a first-in-class anti-CCL2 antibody. CNTO 328 is in development for Castleman's disease (Phase I), multiple myeloma (first-, second- and third-line MM; Phase II), hormone-refractory prostate cancer (Phase II) and supportive care. Clinical responses and disease stabilisation have been observed in MM patients treated with the compound, which has been shown to be safe, well tolerated and biologically active by inducing a rapid and profound normalisation of C-reactive peptides (CRP) in various tumours. J&J plans the filing of CNTO 328 for Castleman’s disease between 2011 and 2013. CNTO 888 is in Phase I development in prostate and ovarian cancer.
Major line extensions include Velcade (bortezomib), developed in partnership with Millennium: The Takeda Oncology Company, in mantle cell lymphoma and non-Hodgkin's lymphoma (NHL). Velcade is already approved in 89 countries, with 61 approvals for front-line MM. A Phase III trial in NHL is under way and Phase II studies, in synergy with Rituxan (rituximab), are producing positive data.
Further, Doxil (doxorubicin liposome injection) is being extended to breast cancer (BC). Already approved in the US for AIDS-related Kaposi's sarcoma, recurrent ovarian cancer (OC) and MM (in combination with Velcade), J&J has submitted an sNDA for the treatment of relapsed BC in combination with Taxotere.
Separately, J&J has filed Yondelis (trabectedin) with the FDA, which was developed in partnership with PharmaMar (Zeltia), for relapsed OC in combination with doxorubicin. Nine trials recently reported provided new data about trabectedin and according to an analysis of data from a Phase III trial, OVA-301, the combination of trabectedin with Doxil/Caelyx results in superior efficacy in patients with relapsed OC with no added decrement to overall health status.
Alice Rossiter - CDN Editor
Promising compounds in early development include CNTO 328, an anti-interleukin-6 monoclonal antibody, and CNTO 888, a first-in-class anti-CCL2 antibody. CNTO 328 is in development for Castleman's disease (Phase I), multiple myeloma (first-, second- and third-line MM; Phase II), hormone-refractory prostate cancer (Phase II) and supportive care. Clinical responses and disease stabilisation have been observed in MM patients treated with the compound, which has been shown to be safe, well tolerated and biologically active by inducing a rapid and profound normalisation of C-reactive peptides (CRP) in various tumours. J&J plans the filing of CNTO 328 for Castleman’s disease between 2011 and 2013. CNTO 888 is in Phase I development in prostate and ovarian cancer.
Major line extensions include Velcade (bortezomib), developed in partnership with Millennium: The Takeda Oncology Company, in mantle cell lymphoma and non-Hodgkin's lymphoma (NHL). Velcade is already approved in 89 countries, with 61 approvals for front-line MM. A Phase III trial in NHL is under way and Phase II studies, in synergy with Rituxan (rituximab), are producing positive data.
Further, Doxil (doxorubicin liposome injection) is being extended to breast cancer (BC). Already approved in the US for AIDS-related Kaposi's sarcoma, recurrent ovarian cancer (OC) and MM (in combination with Velcade), J&J has submitted an sNDA for the treatment of relapsed BC in combination with Taxotere.
Separately, J&J has filed Yondelis (trabectedin) with the FDA, which was developed in partnership with PharmaMar (Zeltia), for relapsed OC in combination with doxorubicin. Nine trials recently reported provided new data about trabectedin and according to an analysis of data from a Phase III trial, OVA-301, the combination of trabectedin with Doxil/Caelyx results in superior efficacy in patients with relapsed OC with no added decrement to overall health status.
Alice Rossiter - CDN Editor
Wednesday, June 10, 2009
Highlights from ASCO
The 45th Annual Meeting of the American Society of Clinical Oncology (ASCO) was held from 29th May to 2nd June, in Orlando, FL. Whilst a previous editorial published in Cancer Drug News (see Issue No. 364 - "Looking ahead to ASCO") noted that the 4,000 study abstracts for this year's meeting had drawn a mainly disappointing response, there were numerous encouraging results reported. Of particular note were positive Phase III data with Roche's Herceptin (trastuzumab) in aggressive gastric cancer (GC), Phase II results with AstraZeneca's olaparib in breast (BC) and ovarian cancer (OC), and final results from a Phase II trial of OncoGenex Pharmaceuticals' OGX-011 in prostate cancer (PCA).
Specifically, trastuzumab showed unprecedented survival in aggressive GC. Data from the international, Phase III ToGA study demonstrated that adding the drug to standard chemotherapy increases average survival by 26 per cent in patients with HER2-positive advanced and inoperable GC compared to chemotherapy alone. This combination is also particularly beneficial to GC patients whose tumours express higher levels of HER2, increasing their median survival to 16 months. Trastuzumab is already well established as the foundation of care for patients with HER2-positive BC and now, based on the ToGA results, Roche is to seek regulatory approvals for its use in HER2-positive advanced GC.
Separately, olaparib showed potential to make significant impact on outcomes of patients with BRCA-deficient BC and OC. Phase II data for the novel, oral poly (ADP-ribose) polymerase (PARP) inhibitor demonstrated that it is effective and well tolerated in women carrying the BRCA1 or BRCA2 gene mutation with BC or advanced OC. PARP inhibition is being explored as a new therapeutic approach in cancers with impaired DNA repair pathways, one example of which is cancers with BRCA deficiency. Indeed, both studies were selected for inclusion in the 'Best of ASCO' scientific programme.
Finally, it was reported that OGX-011 provides survival benefit to PCA patients. OncoGenex presented final results from a Phase II trial, with analyses indicating a survival benefit in PCA patients treated with the compound in combination with docetaxel compared to docetaxel alone. Patients treated with OGX-011 had a rate of death 51 per cent lower than those treated with docetaxel alone. Scott Cormack, President and CEO of OncoGenex, noted that a 39 per cent reduction in death, consistent with the previously-disclosed preliminary analysis, would be a significant advancement for treatment in this patient population, adding: "the multivariate analysis shows an even greater reduction in death rate than our preliminary data and increases our confidence that we are seeing a real and meaningful survival benefit for patients treated with OGX-011...these data clearly justify advancing to Phase III development, and we expect these data will be key in our partnering discussions for future clinical development and potential commercialisation."
Alice Rossiter - Cancer Drug News Editor
Specifically, trastuzumab showed unprecedented survival in aggressive GC. Data from the international, Phase III ToGA study demonstrated that adding the drug to standard chemotherapy increases average survival by 26 per cent in patients with HER2-positive advanced and inoperable GC compared to chemotherapy alone. This combination is also particularly beneficial to GC patients whose tumours express higher levels of HER2, increasing their median survival to 16 months. Trastuzumab is already well established as the foundation of care for patients with HER2-positive BC and now, based on the ToGA results, Roche is to seek regulatory approvals for its use in HER2-positive advanced GC.
Separately, olaparib showed potential to make significant impact on outcomes of patients with BRCA-deficient BC and OC. Phase II data for the novel, oral poly (ADP-ribose) polymerase (PARP) inhibitor demonstrated that it is effective and well tolerated in women carrying the BRCA1 or BRCA2 gene mutation with BC or advanced OC. PARP inhibition is being explored as a new therapeutic approach in cancers with impaired DNA repair pathways, one example of which is cancers with BRCA deficiency. Indeed, both studies were selected for inclusion in the 'Best of ASCO' scientific programme.
Finally, it was reported that OGX-011 provides survival benefit to PCA patients. OncoGenex presented final results from a Phase II trial, with analyses indicating a survival benefit in PCA patients treated with the compound in combination with docetaxel compared to docetaxel alone. Patients treated with OGX-011 had a rate of death 51 per cent lower than those treated with docetaxel alone. Scott Cormack, President and CEO of OncoGenex, noted that a 39 per cent reduction in death, consistent with the previously-disclosed preliminary analysis, would be a significant advancement for treatment in this patient population, adding: "the multivariate analysis shows an even greater reduction in death rate than our preliminary data and increases our confidence that we are seeing a real and meaningful survival benefit for patients treated with OGX-011...these data clearly justify advancing to Phase III development, and we expect these data will be key in our partnering discussions for future clinical development and potential commercialisation."
Alice Rossiter - Cancer Drug News Editor
Thursday, June 4, 2009
Early collaboration: a sign of the times?
Touted as a first-of-its-kind deal, Merck & Co and AstraZeneca have teamed up to research a novel combination anticancer regimen composed of two investigational compounds, MK-2206 and AZD6244 (ARRY-886). The collaboration, which is unusual as it involves two drugs so far from approval, will investigate the agents in a Phase I safety and tolerability trial.
Most combination regimens are investigated once the compounds have either progressed to late-stage development or are already commercially available. This new agreement breaks from that mould as the companies appear to have overcome many of the sticking points that have previously prevented this type of interaction between big pharma. The reason that few development agreements between large companies are signed is that they are extremely complicated. Issues concerning control, valuation and overlap with other projects all present hurdles. Then there is the question of working with your competitor, something that is not encouraged.
But it appears that this deal was struck not because the companies were actively seeking such collaboration, rather a chance encounter at an airport in November 2007 led to it happening. Reports suggest that two scientists, one from Merck and the other from AstraZeneca, got talking at airport security about their respective programmes and the rationale for combining them.
Merck's MK-2206 is the most advanced AKT inhibitor in development. AKT acts downstream of PI3K in the PI3K/PTEN/AKT signalling pathway. AstraZeneca's AZD6244 targets MEK, which plays an important role in a parallel signalling pathway. Laboratory evidence has suggested that the two compounds given in combination could have a much more potent affect against tumours than each agent separately. Even though AstraZencea was also working on its own AKT inhibitor and Merck was developing a drug to block MEK, the companies determined that collaborating would offer a quicker route to market.
So, how will the partnership progress? The companies have agreed to jointly fund a Phase I trial, after which they will consider further clinical development. If the two companies wish to eventually develop a fixed-dose combination then they may have to expand their relationship to possibly include multiple compounds or entire pathways. It could be that an initial goal would be to have each company move a drug through development to market with an approved label supporting use of the other agent in combination. Indeed, if this deal works, then it may pave the way for future similar collaborations.
Sadly, this will be my last issue as Editor of Cancer Drug News as I am moving on to pursue new challenges within the pharma news industry. I hope that you have found the service a valuable information source and I am sure that the new Editor, Alice Rossiter, will continue to uphold the standards of coverage that you as a reader are used to.
Matthew Dennis - Editor, Cancer Drug News
Most combination regimens are investigated once the compounds have either progressed to late-stage development or are already commercially available. This new agreement breaks from that mould as the companies appear to have overcome many of the sticking points that have previously prevented this type of interaction between big pharma. The reason that few development agreements between large companies are signed is that they are extremely complicated. Issues concerning control, valuation and overlap with other projects all present hurdles. Then there is the question of working with your competitor, something that is not encouraged.
But it appears that this deal was struck not because the companies were actively seeking such collaboration, rather a chance encounter at an airport in November 2007 led to it happening. Reports suggest that two scientists, one from Merck and the other from AstraZeneca, got talking at airport security about their respective programmes and the rationale for combining them.
Merck's MK-2206 is the most advanced AKT inhibitor in development. AKT acts downstream of PI3K in the PI3K/PTEN/AKT signalling pathway. AstraZeneca's AZD6244 targets MEK, which plays an important role in a parallel signalling pathway. Laboratory evidence has suggested that the two compounds given in combination could have a much more potent affect against tumours than each agent separately. Even though AstraZencea was also working on its own AKT inhibitor and Merck was developing a drug to block MEK, the companies determined that collaborating would offer a quicker route to market.
So, how will the partnership progress? The companies have agreed to jointly fund a Phase I trial, after which they will consider further clinical development. If the two companies wish to eventually develop a fixed-dose combination then they may have to expand their relationship to possibly include multiple compounds or entire pathways. It could be that an initial goal would be to have each company move a drug through development to market with an approved label supporting use of the other agent in combination. Indeed, if this deal works, then it may pave the way for future similar collaborations.
Sadly, this will be my last issue as Editor of Cancer Drug News as I am moving on to pursue new challenges within the pharma news industry. I hope that you have found the service a valuable information source and I am sure that the new Editor, Alice Rossiter, will continue to uphold the standards of coverage that you as a reader are used to.
Matthew Dennis - Editor, Cancer Drug News
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