One of the major events scheduled for 2009 is the finalisation of Roche's acquisition of Genentech. Having been initially outlined in July 2008, when Roche proposed to acquire the outstanding publicly-held interest in Genentech for US$89.00 per share in cash, or a total payment of approximately US$43.7 billion, the deal has since stalled. After considering the offer, Genentech concluded that Roche's proposal significantly undervalued the company.
At the time, the offer represented a one-day premium of 8.8 per cent to Genentech's closing price of US$81.82 on 18th July and a one-month premium of 19.0 per cent to Genentech's closing price of US$74.76 on 20th June. However, many analysts predicted that the move undervalued the company and saw Genentech's refusal coming, pricing the company higher at between US$100.00 and US$120.00 per share. Genentech shares have recently been trading between US$81.00 and US$84.00.
With both companies refusing to move, the current situation could ultimately work in either's favour. With Roche drawing out the process, it may be possible to extract a lower price for Genentech's remaining shares. However, it looks more likely that a delay will benefit Genentech shareholders as final results from the NSABP C-08 study of Avastin (bevacizumab) plus chemotherapy in adjuvant early-stage colorectal cancer are expected in the first half of 2009. Following an interim analysis in October 2008, the independent Data Monitoring Committee overseeing the trial recommended that the study continued as planned. Investors are watching the study closely since it may open up a major new market for Avastin and the news may strengthen Genentech's position when negotiating a higher bid from Roche. Additional results are expected from studies investigating Avastin in breast cancer and Rituxan (rituximab) as a potential lupus treatment, possibly further strengthening Genentech's case.
With the current financial climate set to continue into 2009, there are sure to be more companies adopting cost saving programmes and re-aligning their activities to focus on drugs that offer near-term value. It is expected that the development of many early-stage drug candidates will be put on hold or discontinued as companies look to streamline and reduce cash expenditure. As was seen in 2008, funding will still be a big hurdle for biotech companies, with many expected to merge and consolidate or disappear altogether.
Access to new drugs looks set to remain an issue. However, in the UK, the National Institute for Health and Clinical Excellence (NICE) has just issued new guidelines, which should improve access to life-extending drugs for people dying from cancer. NICE appraisal committees will now follow the new guidelines, which were drawn up following a public consultation, when reviewing treatments that may extend the lives of patients who are terminally ill.
The guidelines cover drugs that would normally be deemed too expensive for standard NHS use and which are licensed for a terminal illness affecting a small number of patients with less than two years to live. The drugs will have to meet set criteria in order to be approved for NHS use, including being shown to extend life by at least three months compared with standard NHS treatment. Experts estimate that some 10,000 cancer patients a year in the UK could benefit from the move. However, how these guidelines are put into practice over the next 12 months will give more of an indication of real impact.
Matthew Dennis - Editor, Cancer Drug News
Wednesday, January 7, 2009
Losers of 2008
As the year begins, it provides an opportunity to reflect on the past 12 months and to highlight those companies and drugs that have not fared so well. Starting off the year badly, as a knock-on effect from 2007, was Novacea, which in April received notification from Schering-Plough of its termination of the collaboration agreement relating to the development of Asentar (DN-101). In 2007, the companies halted the Phase III ASCENT-2 trial of Asentar for the treatment of patients with androgen-independent prostate cancer (PCA), due to an imbalance of deaths between the two treatment arms. The companies then suspended enrolment in other ongoing trials involving the drug. There was a glimmer of hope for Novacea later in the year as it entered into a merger agreement with Transcept Pharmaceuticals, however Asentar was offered no such lifeline and there are no plans to resurrect it.
As with previous years, cancer vaccines promised much in 2008, but again failed to deliver. Favrille's Phase III registration trial for Specifid (mitumprotimut-T) administered following Rituxan (rituximab) in patients with follicular B-cell non-Hodgkin's lymphoma failed to show a statistically significant improvement in the primary endpoint of time-to-progression. Due to the results, Favrille is discontinuing development of the vaccine and is currently evaluating steps to conserve cash and recognise value on its assets, which include a reverse merger with MyMedicalRecords.com. Cell Genesys also suffered as the company, along with Takeda and its wholly-owned subsidiary, Millennium Pharmaceuticals, suspended further development of GVAX immunotherapy for PCA. In October, Cell Genesys terminated the Phase III VITAL-1 trial of GVAX in patients with asymptomatic, metastatic hormone-refractory PCA following an analysis, which indicated that the trial had a <30 class="blsp-spelling-error" id="SPELLING_ERROR_24">Genesys to implement a substantial restructuring plan, which will include the loss of around 80 per cent of its employees.
Other drugs to fail in Phase III included Taiho Pharmaceutical's S-1 in advanced gastric cancer, which caused sanofi-aventis to return its development and commercialisation rights to the oral anticancer agent, as well as Progen Pharmaceuticals' PI-88 in hepatocellular carcinoma, for which the company cited reduced commercial opportunities. A further surprise came when the FDA notified Introgen Therapeutics that its BLA for Advexin (contusugene ladenovec), the company's targeted p53 tumour suppressor gene therapy for the treatment of recurrent, refractory squamous cell carcinoma of the head and neck (SCCHN), was not sufficiently complete and would not be filed at this time. Introgen intends to appeal this refuse to file decision and is reviewing the various options available to it. The decision came as a surprise, as earlier in August, the EMEA accepted for review Gendux Molecular's (Introgen) MAA for Advexin for the treatment of recurrent, refractory SCCHN.
But perhaps the biggest loser of the year was Bristol-Myers Squibb, which lost out to Eli Lilly in the race to takeover ImClone Systems. However, BMS did receive approximately US$1 billion in cash following the acquisition, an amount that in the current financial climate is perhaps as valuable.
Matthew Dennis - Editor, Cancer Drug News
As with previous years, cancer vaccines promised much in 2008, but again failed to deliver. Favrille's Phase III registration trial for Specifid (mitumprotimut-T) administered following Rituxan (rituximab) in patients with follicular B-cell non-Hodgkin's lymphoma failed to show a statistically significant improvement in the primary endpoint of time-to-progression. Due to the results, Favrille is discontinuing development of the vaccine and is currently evaluating steps to conserve cash and recognise value on its assets, which include a reverse merger with MyMedicalRecords.com. Cell Genesys also suffered as the company, along with Takeda and its wholly-owned subsidiary, Millennium Pharmaceuticals, suspended further development of GVAX immunotherapy for PCA. In October, Cell Genesys terminated the Phase III VITAL-1 trial of GVAX in patients with asymptomatic, metastatic hormone-refractory PCA following an analysis, which indicated that the trial had a <30 class="blsp-spelling-error" id="SPELLING_ERROR_24">Genesys to implement a substantial restructuring plan, which will include the loss of around 80 per cent of its employees.
Other drugs to fail in Phase III included Taiho Pharmaceutical's S-1 in advanced gastric cancer, which caused sanofi-aventis to return its development and commercialisation rights to the oral anticancer agent, as well as Progen Pharmaceuticals' PI-88 in hepatocellular carcinoma, for which the company cited reduced commercial opportunities. A further surprise came when the FDA notified Introgen Therapeutics that its BLA for Advexin (contusugene ladenovec), the company's targeted p53 tumour suppressor gene therapy for the treatment of recurrent, refractory squamous cell carcinoma of the head and neck (SCCHN), was not sufficiently complete and would not be filed at this time. Introgen intends to appeal this refuse to file decision and is reviewing the various options available to it. The decision came as a surprise, as earlier in August, the EMEA accepted for review Gendux Molecular's (Introgen) MAA for Advexin for the treatment of recurrent, refractory SCCHN.
But perhaps the biggest loser of the year was Bristol-Myers Squibb, which lost out to Eli Lilly in the race to takeover ImClone Systems. However, BMS did receive approximately US$1 billion in cash following the acquisition, an amount that in the current financial climate is perhaps as valuable.
Matthew Dennis - Editor, Cancer Drug News
Thursday, December 18, 2008
Winners of 2008
As the year draws to a close, there is just time to reflect on the past 12 months and to highlight those companies and drugs that have triumphed and failed. With only seven major new drug approvals in the US and Europe, compared to 11 in 2007, it would seem that the pharmaceutical industry and regulators are suffering from the knock-on effects of the current financial climate, where prudence is now key.
The year got off to a good start, when in January the EC granted marketing approval to Abraxis BioScience's Abraxane (paclitaxel protein-bound particles for injectable suspension; albumin-bound) for the treatment of metastatic breast cancer in patients who have failed first-line treatment for metastatic disease and for whom standard, anthracycline-containing therapy is not indicated. The first US approval came in the form of Cephalon's Treanda (bendamustine) for Injection, for the treatment of patients with chronic lymphocytic leukaemia (CLL) in March. Later in the year, the FDA also approved bendamustine for the treatment of patients with indolent B-cell non-Hodgkin's lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. In October, the EC granted a full marketing authorisation, in the form of a positive Commission Decision, for EpiCept's Ceplene (histamine dihydrochloride) for the remission maintenance and prevention of relapse in adult patients with acute myeloid leukaemia in first remission.
The major winners of 2008 were definitely in the field of supportive care for cancer. In January, the EC and FDA approved Merck & Co's fosaprepitant dimeglumine (MK-0517) for Injection, an intravenous therapy for the prevention of chemotherapy (CT)-induced nausea and vomiting (CINV). Available as Emend in the US and Ivemend in the EU, the drug was approved for use in combination with other anti-emetic medicines for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately- and highly-emetogenic cancer CT. A further approval came in September, as the FDA approved ProStrakan's Sancuso (granisetron), a novel, patent-protected transdermal patch for the prevention of CINV; the product was launched in the US in November.
Another approval to support cancer patients came in April when the EC granted marketing authorisation to Cephalon's Effentora, a buccal tablet formulation of fentanyl, for the treatment of breakthrough cancer pain in adult patients who are already receiving maintenance opioid therapy for chronic pain. More good news came as both the FDA and EC approved Progenics Pharmaceuticals/Wyeth Pharmaceuticals' Relistor (methylnaltrexone injection), in April and July, respectively, for subcutaneous use for the treatment of opioid-induced constipation in patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. In what could be the final approval of the year, in December, the FDA granted marketing authorisation to Genzyme's Mozobil (plerixafor injection), a drug intended to be used in combination with G-CSF to mobilise haematopoietic stem cells to the bloodstream for collection and subsequent autologous transplantation in patients with NHL and multiple myeloma. Hopefully 2009 will be a more fruitful year.
Matthew Dennis - Editor, Cancer Drug News
The year got off to a good start, when in January the EC granted marketing approval to Abraxis BioScience's Abraxane (paclitaxel protein-bound particles for injectable suspension; albumin-bound) for the treatment of metastatic breast cancer in patients who have failed first-line treatment for metastatic disease and for whom standard, anthracycline-containing therapy is not indicated. The first US approval came in the form of Cephalon's Treanda (bendamustine) for Injection, for the treatment of patients with chronic lymphocytic leukaemia (CLL) in March. Later in the year, the FDA also approved bendamustine for the treatment of patients with indolent B-cell non-Hodgkin's lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. In October, the EC granted a full marketing authorisation, in the form of a positive Commission Decision, for EpiCept's Ceplene (histamine dihydrochloride) for the remission maintenance and prevention of relapse in adult patients with acute myeloid leukaemia in first remission.
The major winners of 2008 were definitely in the field of supportive care for cancer. In January, the EC and FDA approved Merck & Co's fosaprepitant dimeglumine (MK-0517) for Injection, an intravenous therapy for the prevention of chemotherapy (CT)-induced nausea and vomiting (CINV). Available as Emend in the US and Ivemend in the EU, the drug was approved for use in combination with other anti-emetic medicines for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately- and highly-emetogenic cancer CT. A further approval came in September, as the FDA approved ProStrakan's Sancuso (granisetron), a novel, patent-protected transdermal patch for the prevention of CINV; the product was launched in the US in November.
Another approval to support cancer patients came in April when the EC granted marketing authorisation to Cephalon's Effentora, a buccal tablet formulation of fentanyl, for the treatment of breakthrough cancer pain in adult patients who are already receiving maintenance opioid therapy for chronic pain. More good news came as both the FDA and EC approved Progenics Pharmaceuticals/Wyeth Pharmaceuticals' Relistor (methylnaltrexone injection), in April and July, respectively, for subcutaneous use for the treatment of opioid-induced constipation in patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. In what could be the final approval of the year, in December, the FDA granted marketing authorisation to Genzyme's Mozobil (plerixafor injection), a drug intended to be used in combination with G-CSF to mobilise haematopoietic stem cells to the bloodstream for collection and subsequent autologous transplantation in patients with NHL and multiple myeloma. Hopefully 2009 will be a more fruitful year.
Matthew Dennis - Editor, Cancer Drug News
Cancer to lead death toll in 2010?
Despite the fact that cancer incidence and death rates for men and women in the developed world continue to decline, cancer is projected to become the leading cause of death worldwide in the year 2010, and low- and middle-income countries will feel the impact of higher cancer incidence and death rates more sharply than industrialised countries.
To coincide with the International Agency for Research on Cancer releasing the new edition of the World Cancer Report, in the US, the nation's leading cancer organisations joined forces at an event called Conquering Cancer: A Global Effort, to focus attention on the growing global cancer burden and discuss efforts needed to address the problem. The American Cancer Society, the Lance Armstrong Foundation and Susan G. Komen for the Cure discussed how each organisation is addressing the global cancer problem and together issued a call to action for the incoming US presidential administration and Congress.
According to the report, the burden of cancer doubled globally between 1975 and 2000. It is estimated that it will double again by 2020 and nearly triple by 2030. This translates to far greater numbers of people living with and dying from the disease. The report estimates that there were some 12 million new cancer diagnoses worldwide in 2008, and more than 7 million people will die from the disease.
The projected numbers for the year 2030 are 20 to 26 million new diagnoses and 13 to 17 million deaths. The growing cancer burden includes global increases of incidence of approximately 1 per cent each year, with larger increases in China, Russia and India. Reasons for the increased rates include adoption of Western habits in less developed countries, such as tobacco use and higher-fat diets, and demographic changes, including a projected population increase of 38 per cent in less developed countries between 2008 and 2030. In addition to increases in cancer incidence and death rates, the report identifies challenges in cancer care, especially in Africa, where pain management and palliative care are very limited because any use of narcotics is prohibited by law in several countries.
The call to action steps issued by the three organisations include: 1) making vaccines that prevent cancer-causing infections more widely available to low-income nations, including efforts to make the human papillomavirus vaccine accessible and affordable; 2) committing to a comprehensive tobacco control approach in the US, which includes taking measures proven effective in reducing smoking rates and having Congress grant the FDA authority to regulate tobacco; 3) ratifying immediately the Framework Convention on Tobacco Control, the first ever global public health treaty that sets forth comprehensive measures to reduce health and economic impacts of tobacco; 4) supporting efforts of non-governmental organisations to build advocacy and resources, empower survivors and reduce suffering in low- to middle-income countries by working with governments, medical professionals and the corporate sector to enable individuals to adopt healthier behaviours; 5) promoting culturally-sensitive risk reduction and education campaigns by leveraging US efforts to help build capacity of non-governmental organisations in other countries; and 6) investing in cancer research and expanding access to prevention and early detection measures in the US, with a specific focus on increasing federal funding of medical research.
Matthew Dennis - Editor, Cancer Drug News
To coincide with the International Agency for Research on Cancer releasing the new edition of the World Cancer Report, in the US, the nation's leading cancer organisations joined forces at an event called Conquering Cancer: A Global Effort, to focus attention on the growing global cancer burden and discuss efforts needed to address the problem. The American Cancer Society, the Lance Armstrong Foundation and Susan G. Komen for the Cure discussed how each organisation is addressing the global cancer problem and together issued a call to action for the incoming US presidential administration and Congress.
According to the report, the burden of cancer doubled globally between 1975 and 2000. It is estimated that it will double again by 2020 and nearly triple by 2030. This translates to far greater numbers of people living with and dying from the disease. The report estimates that there were some 12 million new cancer diagnoses worldwide in 2008, and more than 7 million people will die from the disease.
The projected numbers for the year 2030 are 20 to 26 million new diagnoses and 13 to 17 million deaths. The growing cancer burden includes global increases of incidence of approximately 1 per cent each year, with larger increases in China, Russia and India. Reasons for the increased rates include adoption of Western habits in less developed countries, such as tobacco use and higher-fat diets, and demographic changes, including a projected population increase of 38 per cent in less developed countries between 2008 and 2030. In addition to increases in cancer incidence and death rates, the report identifies challenges in cancer care, especially in Africa, where pain management and palliative care are very limited because any use of narcotics is prohibited by law in several countries.
The call to action steps issued by the three organisations include: 1) making vaccines that prevent cancer-causing infections more widely available to low-income nations, including efforts to make the human papillomavirus vaccine accessible and affordable; 2) committing to a comprehensive tobacco control approach in the US, which includes taking measures proven effective in reducing smoking rates and having Congress grant the FDA authority to regulate tobacco; 3) ratifying immediately the Framework Convention on Tobacco Control, the first ever global public health treaty that sets forth comprehensive measures to reduce health and economic impacts of tobacco; 4) supporting efforts of non-governmental organisations to build advocacy and resources, empower survivors and reduce suffering in low- to middle-income countries by working with governments, medical professionals and the corporate sector to enable individuals to adopt healthier behaviours; 5) promoting culturally-sensitive risk reduction and education campaigns by leveraging US efforts to help build capacity of non-governmental organisations in other countries; and 6) investing in cancer research and expanding access to prevention and early detection measures in the US, with a specific focus on increasing federal funding of medical research.
Matthew Dennis - Editor, Cancer Drug News
Wednesday, December 3, 2008
More teens needed for trials
A new UK study has highlighted the small number of teenagers who are enrolled in clinical trials for cancer, despite the benefits of being involved. Inclusion in studies has been shown to improve cancer survival, because it provides access to new drugs, better quality of care through frequent monitoring and access to a wider group of specialists. The results of the work have been published in the 1st December online edition of the British Journal of Cancer (10.1038/sj.bjc.6604751).
Scientists from University College London analysed enrolment in Phase III trials from April 2005 to March 2007 involving teenagers and young adults (TYA), as well as children. All of the young patients involved in trials had been diagnosed with leukaemia, lymphoma, brain and central nervous system, bone sarcomas or male germ cell tumours. The researchers found that only 25.2 per cent of 15 to 19-year-olds and 13.1 per cent of 20 to 24-year-olds were enrolled in clinical trials, compared with 43.2 per cent of ten to 14-year-olds. Rates increased among ten to 14-year-olds and 15 to 19-year-olds during April 2006 to March 2007 compared with the previous 12 months, but fell among 20 to 24-year-olds.
The investigators noted that there were four trials available for patients with CNS tumours, yet no over-16s were enrolled in these trials. They also observed that over-15s were much less likely to take part in clinical trials in England than children and younger teenagers. The variations in open trials, trial age eligibility criteria and extent of trial activation in treatment centres in part explain this observation. However, other possible influences, such as difficulties associated with the consent of TYA require further evaluation.
Study leader Dr Lorna Fern, who co-ordinates research into TYA with cancer at the National Cancer Research Institute has said that the US and Australia had also reported a similar trend. Young people are constantly falling through the gap between paediatric and adult cancer specialists and there are not enough trials for the types of cancers that affect them. This is an important study that can be used as the base on which progress is measured in the UK. Before now, it was not known how many young people with cancer were recruited onto clinical trials. It is hoped that in the future, closer dialogue between those involved in planning and running trials for children and for adults will improve trial availability and recruitment.
Amending the age eligibility criteria is one possible solution, although it may not completely address the problem of recruiting TYA. In the EURAMOS-1 trial (an international osteosarcoma trial), a fall off in recruitment has been seen beyond the age of 15, despite an age eligibility criteria which spans the whole paediatric and TYA population. Average accrual to EURAMOS-1 in England, Scotland and Wales has demonstrated a decline in accrual from 42.7 per cent for patients aged ten to 14 years, 38.3 per cent for those aged 15 to 19, and 15.7 per cent of patients aged 20 to 24 from 2005 to 2008.
It is feared that significant improvements in outcomes from cancer for TYA will remain elusive without a coalition of forces including funders, policy makers, biologists, clinicians and patients.
Matthew Dennis - Editor, Cancer Drug News
Scientists from University College London analysed enrolment in Phase III trials from April 2005 to March 2007 involving teenagers and young adults (TYA), as well as children. All of the young patients involved in trials had been diagnosed with leukaemia, lymphoma, brain and central nervous system, bone sarcomas or male germ cell tumours. The researchers found that only 25.2 per cent of 15 to 19-year-olds and 13.1 per cent of 20 to 24-year-olds were enrolled in clinical trials, compared with 43.2 per cent of ten to 14-year-olds. Rates increased among ten to 14-year-olds and 15 to 19-year-olds during April 2006 to March 2007 compared with the previous 12 months, but fell among 20 to 24-year-olds.
The investigators noted that there were four trials available for patients with CNS tumours, yet no over-16s were enrolled in these trials. They also observed that over-15s were much less likely to take part in clinical trials in England than children and younger teenagers. The variations in open trials, trial age eligibility criteria and extent of trial activation in treatment centres in part explain this observation. However, other possible influences, such as difficulties associated with the consent of TYA require further evaluation.
Study leader Dr Lorna Fern, who co-ordinates research into TYA with cancer at the National Cancer Research Institute has said that the US and Australia had also reported a similar trend. Young people are constantly falling through the gap between paediatric and adult cancer specialists and there are not enough trials for the types of cancers that affect them. This is an important study that can be used as the base on which progress is measured in the UK. Before now, it was not known how many young people with cancer were recruited onto clinical trials. It is hoped that in the future, closer dialogue between those involved in planning and running trials for children and for adults will improve trial availability and recruitment.
Amending the age eligibility criteria is one possible solution, although it may not completely address the problem of recruiting TYA. In the EURAMOS-1 trial (an international osteosarcoma trial), a fall off in recruitment has been seen beyond the age of 15, despite an age eligibility criteria which spans the whole paediatric and TYA population. Average accrual to EURAMOS-1 in England, Scotland and Wales has demonstrated a decline in accrual from 42.7 per cent for patients aged ten to 14 years, 38.3 per cent for those aged 15 to 19, and 15.7 per cent of patients aged 20 to 24 from 2005 to 2008.
It is feared that significant improvements in outcomes from cancer for TYA will remain elusive without a coalition of forces including funders, policy makers, biologists, clinicians and patients.
Matthew Dennis - Editor, Cancer Drug News
Thursday, November 27, 2008
Last chance for Iressa?
Results from the Phase III INTEREST (IRESSA Non-small-cell lung cancer Trial Evaluating REsponse and Survival against Taxotere) study, published in the 22nd November edition of The Lancet (2008;372:1809-1818), have shown that patients with pretreated advanced non-small cell lung cancer (NSCLC) who received the oral anticancer drug, Iressa (gefitinib), had comparable survival to those treated with intravenous docetaxel. In addition, gefitinib had a more favourable tolerability profile than docetaxel and significantly more gefitinib-treated patients had an improvement in quality of life.
These results follow previous disappointing data for the drug in the ISEL (IRESSA Survival Evaluation in Lung cancer) study, where gefitinib failed to demonstrate a survival advantage versus placebo in NSCLC patients. This led to a severe restriction on the use of the drug in the US and also to AstraZeneca withdrawing its MAA in Europe. As such, gefitinib is not currently licensed in the EU, however on 2nd May, AstraZeneca submitted an MAA to the EMEA seeking approval as a treatment for locally-advanced or metastatic NSCLC patients pretreated with platinum chemotherapy (CT). The application is based on data from the INTEREST study and is the first time a targeted therapy, an EGFr tyrosine kinase inhibitor, has proven non-inferiority for overall survival (OS) relative to CT in patients with pretreated advanced NSCLC.
The INTEREST study was a randomised, open-label, parallel-group trial evaluating survival with gefitinib versus docetaxel in 1,466 patients with locally-advanced or metastatic recurrent NSCLC who had previously received platinum-based CT. Patients were randomly assigned to receive gefitinib (250mg/day; n=733) or docetaxel (75mg/m2; n=733). The primary objective was to compare OS between the groups with co-primary analyses to assess non-inferiority in the overall per-protocol population and superiority in patients with high EGFr-gene-copy number in the intention-to-treat population.
In the study, 1,433 patients were analysed per protocol (723 in the gefitinib group and 710 in the docetaxel group). Non-inferiority of gefitinib compared with docetaxel was confirmed for OS (593 vs 576 events; hazard ratio [HR]=1.02; 96% CI, 0.905 to 1.150, meeting the predefined non-inferiority criterion; median survival 7.6 vs 8.0 months). Superiority of gefitinib in patients with high EGFr-gene-copy number (85 vs 89 patients) was not proven (72 vs 71 events; HR=1.09; 95% CI, 0.78 to 1.51; p=0.62; median survival 8.4 vs 7.5 months).
Will these new data signal a resurrection for the drug? With such mixed results for gefitinib, it is hard to imagine doctors altering their prescribing habits on the basis of the INTEREST data alone, especially when there are many of other options available for treating LC patients. Tarceva (erlotinib), another EGFr inhibitor, is available, as is Avastin (bevacizumab), with more on the horizon, including Erbitux (cetuximab). One thing that could save gefitinb is the use of pharmacogenomics and a test to predict which patients would be suitable for treatment with the drug. However, this is an expensive and time-consuming undertaking, one that AstraZeneca may not see as financially rewarding or competitive as there are already EGFr inhibitors available, such as cetuximab and Vectibix (panitumumab), that are marketed alongside companion diagnostics. As such, INTEREST could be gefitinib’s final chance of success.
Matthew Dennis - Editor, Cancer Drug News
These results follow previous disappointing data for the drug in the ISEL (IRESSA Survival Evaluation in Lung cancer) study, where gefitinib failed to demonstrate a survival advantage versus placebo in NSCLC patients. This led to a severe restriction on the use of the drug in the US and also to AstraZeneca withdrawing its MAA in Europe. As such, gefitinib is not currently licensed in the EU, however on 2nd May, AstraZeneca submitted an MAA to the EMEA seeking approval as a treatment for locally-advanced or metastatic NSCLC patients pretreated with platinum chemotherapy (CT). The application is based on data from the INTEREST study and is the first time a targeted therapy, an EGFr tyrosine kinase inhibitor, has proven non-inferiority for overall survival (OS) relative to CT in patients with pretreated advanced NSCLC.
The INTEREST study was a randomised, open-label, parallel-group trial evaluating survival with gefitinib versus docetaxel in 1,466 patients with locally-advanced or metastatic recurrent NSCLC who had previously received platinum-based CT. Patients were randomly assigned to receive gefitinib (250mg/day; n=733) or docetaxel (75mg/m2; n=733). The primary objective was to compare OS between the groups with co-primary analyses to assess non-inferiority in the overall per-protocol population and superiority in patients with high EGFr-gene-copy number in the intention-to-treat population.
In the study, 1,433 patients were analysed per protocol (723 in the gefitinib group and 710 in the docetaxel group). Non-inferiority of gefitinib compared with docetaxel was confirmed for OS (593 vs 576 events; hazard ratio [HR]=1.02; 96% CI, 0.905 to 1.150, meeting the predefined non-inferiority criterion; median survival 7.6 vs 8.0 months). Superiority of gefitinib in patients with high EGFr-gene-copy number (85 vs 89 patients) was not proven (72 vs 71 events; HR=1.09; 95% CI, 0.78 to 1.51; p=0.62; median survival 8.4 vs 7.5 months).
Will these new data signal a resurrection for the drug? With such mixed results for gefitinib, it is hard to imagine doctors altering their prescribing habits on the basis of the INTEREST data alone, especially when there are many of other options available for treating LC patients. Tarceva (erlotinib), another EGFr inhibitor, is available, as is Avastin (bevacizumab), with more on the horizon, including Erbitux (cetuximab). One thing that could save gefitinb is the use of pharmacogenomics and a test to predict which patients would be suitable for treatment with the drug. However, this is an expensive and time-consuming undertaking, one that AstraZeneca may not see as financially rewarding or competitive as there are already EGFr inhibitors available, such as cetuximab and Vectibix (panitumumab), that are marketed alongside companion diagnostics. As such, INTEREST could be gefitinib’s final chance of success.
Matthew Dennis - Editor, Cancer Drug News
Thursday, November 20, 2008
Targeted drugs reduce attrition rates
The results of a new study published in the 14th November online edition of Nature Reviews Drug Discovery (10.1038/nrd2758) suggest that advances in drug development have led to an increase in the number of drugs reaching cancer patients. Scientists from Cancer Research Technology (CRT; Cancer Research UK [CRUK]) obtained data on 974 cancer drugs in clinical development, and calculated that there was a probability that 18 per cent of those entering the clinic would make it to market. Previously it was estimated that in some studies only 5 per cent of cancer drugs in the pipeline become standard treatments for the disease.
The data search was limited to agents which entered Phase I trials after January 1995 and before September 2007, of which 137 are the molecularly-targeted drug class, kinase inhibitors. The research showed that kinase inhibitors were almost three-times more likely to reach patients than other types of anticancer drug. The investigators believe that a better understanding of the basic biology of cancer has enabled the development of this type of new drug, which includes Herceptin (trastuzumab) for breast cancer and Glivec/Gleevec (imatinib) for leukaemia.
The study highlights the fact that understanding more about the basic biology of cancer is making a real difference to the success rate of new anticancer drug development. Additionally, improved drug-discovery processes and advances in medicinal chemistry have also contributed to better success rates of drugs in development. Furthermore, better understanding of a patient's genetic make-up and how they will respond to certain drugs has led to improvements in clinical trial design.As drug development continues to advance, minimising the number of drugs which fail to make it to market will remain key as the cost of discovery and development of those drugs which do not reach market is borne by those that do. The true cost of a drug reaching the market has recently been estimated to be US$0.8 billion to US$1.0 billion.
According to one of the study authors, Professor Herbie Newell, Director of Translational Research at CRUK: "We strongly believe that both industry and academia must improve the availability of data related to failed as well as successful drug development programmes. The sharing of such information can only be beneficial for clinical, scientific and commercial reasons, and will help measure our progress as well as pinpoint areas for improvement."
Historically, the oncology pipeline has been largely made up of small-molecule cytotoxic drugs, which have a low therapeutic index and can fail in clinical trials due to toxicity or efficacy reasons. The recent explosion of information coming from work into understanding the molecular basis of cancer has led to an increase of drugs targeting specific pathways, drugs that are specifically designed to treat cancer, rather than randomly killing proliferating cells. As more information becomes available and newer drugs that are better targeted move into the pipeline, the attrition rate for cancer drugs may reach levels seen with other therapy areas, such as cardiovascular disease where 20 per cent of agents in development reach the market.
Matthew Dennis - Editor, Cancer Drug News
The data search was limited to agents which entered Phase I trials after January 1995 and before September 2007, of which 137 are the molecularly-targeted drug class, kinase inhibitors. The research showed that kinase inhibitors were almost three-times more likely to reach patients than other types of anticancer drug. The investigators believe that a better understanding of the basic biology of cancer has enabled the development of this type of new drug, which includes Herceptin (trastuzumab) for breast cancer and Glivec/Gleevec (imatinib) for leukaemia.
The study highlights the fact that understanding more about the basic biology of cancer is making a real difference to the success rate of new anticancer drug development. Additionally, improved drug-discovery processes and advances in medicinal chemistry have also contributed to better success rates of drugs in development. Furthermore, better understanding of a patient's genetic make-up and how they will respond to certain drugs has led to improvements in clinical trial design.As drug development continues to advance, minimising the number of drugs which fail to make it to market will remain key as the cost of discovery and development of those drugs which do not reach market is borne by those that do. The true cost of a drug reaching the market has recently been estimated to be US$0.8 billion to US$1.0 billion.
According to one of the study authors, Professor Herbie Newell, Director of Translational Research at CRUK: "We strongly believe that both industry and academia must improve the availability of data related to failed as well as successful drug development programmes. The sharing of such information can only be beneficial for clinical, scientific and commercial reasons, and will help measure our progress as well as pinpoint areas for improvement."
Historically, the oncology pipeline has been largely made up of small-molecule cytotoxic drugs, which have a low therapeutic index and can fail in clinical trials due to toxicity or efficacy reasons. The recent explosion of information coming from work into understanding the molecular basis of cancer has led to an increase of drugs targeting specific pathways, drugs that are specifically designed to treat cancer, rather than randomly killing proliferating cells. As more information becomes available and newer drugs that are better targeted move into the pipeline, the attrition rate for cancer drugs may reach levels seen with other therapy areas, such as cardiovascular disease where 20 per cent of agents in development reach the market.
Matthew Dennis - Editor, Cancer Drug News
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