The UK's National Institute for Health and Clinical Excellence (NICE) has issued its final appraisal document recommending the use of Pfizer's Sutent (sunitinib) as a first-line treatment for patients with metastatic renal cell carcinoma (RCC). However, sunitinib is the only one of four drugs being appraised that has been preliminarily cleared for use on the NHS, once again raising the question of drug access in the UK compared to the rest of Europe.
NICE is also currently appraising the use of Roche/Genentech's Avastin (bevacizumab), Bayer/Onyx Pharmaceuticals' Nexavar (sorafenib) and Wyeth's Torisel (temsirolimus) for the treatment of advanced and/or metastatic RCC. Following the independent advisory Committee meeting on 14th January, NICE has decided to split this appraisal in two in order to get guidance out to the NHS as quickly as possible. In the first appraisal, sunitinib is recommended as a first-line treatment option in advanced and/or metastatic RCC for patients who are suitable for immunotherapy with an ECOG performance status of 0 or 1. Sunitinib demonstrated a significant improvement in progression-free survival versus interferon alpha. The median survival of patients treated with sunitinib exceeded two years. In September 2008, NICE had issued an appraisal consultation document that advised against the use of all four medicines for the treatment of advanced and/or metastatic RCC. The latest announcement reverses NICE's previous recommendation regarding the coverage of sunitinib, making it the only one of the four medicines under review, that is so far recommended for coverage.
Sunitinib, an oral multi-kinase inhibitor, was first approved in January 2006 for advanced RCC. The drug works by blocking multiple molecular targets implicated in the growth, proliferation and spread of cancer. Pfizer has agreed a patient access scheme with the Department of Health, in which the first treatment cycle of sunitinib is free to the NHS.
In the second appraisal, bevacizumab, sorafenib and temsirolimus are not recommended as first-line treatment options for advanced and/or metastatic RCC. In addition, the two drugs also licensed for second-line treatment of advanced or metastatic RCC, sorafenib and sunitinib, are not recommended for this indication. Guidance on bevacizumab, sorafenib and temsirolimus for first-line treatment and sorafenib and sunitinib for the second-line treatment of RCC is available for public consultation via NICE until 4th March.
In a statement from Wyeth, the company commented that it believes that denying patients access to the benefits of temsirolimus in extending life-expectancy compared to standard existing therapy is a devastating and cruel blow to patients and their families. Temsirolimus, despite being found to be clinically effective, has been deemed not to be cost-effective in the current assessment.
Similarly disappointing news was announced in Scotland, as the Scottish Medicines Consortium (SMC) published its guidance on the use of GSK's Tyverb (lapatinib) and Eli Lilly's Alimta (pemetrexed), ruling that in both cases the manufacturer did not present a sufficiently robust economic case to gain acceptance. Lapatinib is approved in Europe, in combination with capecitabine, for the treatment of patients with advanced or metastatic breast cancer, while pemetrexed is indicated, in combination with cisplatin, for the first-line treatment of patients with locally-advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology. Despite clinical evidence that the two drugs can extend patients' lives by around two months and six weeks, respectively, the price that this comes at is still not seen as cost-effective.
Matthew Dennis - Editor, Cancer Drug News
Thursday, February 19, 2009
Wednesday, February 4, 2009
ATLAS meets primary endpoint
The Phase III ATLAS (AVF3671g) study investigating Tarceva (erlotinib) in combination with Avastin (bevacizumab) as maintenance therapy following initial treatment with bevacizumab plus chemotherapy (CT) in advanced non-small cell lung cancer (NSCLC) has met its primary endpoint. The trial was stopped early on the recommendation of an independent Data Safety Monitoring Board after a preplanned interim analysis showed that combining erlotinib and bevacizumab significantly extended the time patients lived without their disease advancing, as defined by progression-free survival (PFS), compared to bevacizumab plus placebo. A preliminary safety analysis showed adverse events were consistent with previous erlotinib and bevacizumab studies, as well as trials evaluating the two medicines together, and no new safety signals were observed.
The global, multi-centre, randomised, double-blind, placebo-controlled study enrolled 1,157 patients with locally-advanced, recurrent or metastatic NSCLC. In order to evaluate patients who are often excluded from bevacizumab-based trials, patients with treated brain metastases, tumours of squamous cell histology that were not centrally located in the lung and those taking blood-thinning medications were eligible for this trial. Subjects were initially treated with four cycles of bevacizumab in combination with the investigators' choice of platinum-based CT regimens (carboplatin+gemcitabine, carboplatin+paclitaxel, carboplatin+docetaxel, cisplatin+vinorelbine, cisplatin+docetaxel or cisplatin+gemcitabine). If their cancer did not progress and they did not experience significant toxicity, patients were then randomised (n=768) to receive maintenance therapy with bevacizumab+erlotinib or bevacizumab+placebo until disease progression.
The study's primary endpoint of PFS, as determined by investigators, was defined as the length of time from randomisation to disease progression or death from any cause. PFS assessment began from the start of the maintenance phase of the study after initial treatment with four cycles of bevacizumab and CT. Secondary endpoints included overall survival (OS), incidence of all adverse events and selected Grade 3 or greater adverse events and incidence of treatment discontinuation for reasons other than disease progression.
An earlier study, called BeTa Lung, which evaluated bevacizumab in combination with erlotinib in patients with advanced NSCLC whose disease had progressed following platinum-based CT, failed to meet its primary endpoint of improving OS compared to erlotinib in combination with placebo. However, there was clear evidence of clinical activity, with improvements in the secondary endpoints of PFS and response rate when bevacizumab was added to erlotinib compared to erlotinib alone. An additional trial, called SATURN, showed that erlotinib delayed disease progression when given as a single agent immediately following treatment with CT, compared to placebo. In ATLAS, patients were initially treated with bevacizumab plus CT followed by the addition of erlotinib to bevacizumab in the maintenance phase. Genentech plans to discuss these data with the FDA to determine next steps.
Avastin is currently approved as first-line treatment in combination with carboplatin and paclitaxel for patients with locally-advanced, non-squamous NSCLC, based on a 25 per cent improvement in OS compared to CT alone (hazard ratio=0.80). Tarceva is currently approved as a treatment for patients with advanced NSCLC who have progressed following treatment with at least one prior CT regimen, based on a 37 per cent improvement in OS compared to placebo (hazard ratio=0.73). OSI Pharmaceuticals markets Tarceva through partnerships with Genentech in the US and Roche throughout the rest of the world. Avastin is jointly marketed by Genentech and Roche.
Matthew Dennis - Editor, Cancer Drug News
The global, multi-centre, randomised, double-blind, placebo-controlled study enrolled 1,157 patients with locally-advanced, recurrent or metastatic NSCLC. In order to evaluate patients who are often excluded from bevacizumab-based trials, patients with treated brain metastases, tumours of squamous cell histology that were not centrally located in the lung and those taking blood-thinning medications were eligible for this trial. Subjects were initially treated with four cycles of bevacizumab in combination with the investigators' choice of platinum-based CT regimens (carboplatin+gemcitabine, carboplatin+paclitaxel, carboplatin+docetaxel, cisplatin+vinorelbine, cisplatin+docetaxel or cisplatin+gemcitabine). If their cancer did not progress and they did not experience significant toxicity, patients were then randomised (n=768) to receive maintenance therapy with bevacizumab+erlotinib or bevacizumab+placebo until disease progression.
The study's primary endpoint of PFS, as determined by investigators, was defined as the length of time from randomisation to disease progression or death from any cause. PFS assessment began from the start of the maintenance phase of the study after initial treatment with four cycles of bevacizumab and CT. Secondary endpoints included overall survival (OS), incidence of all adverse events and selected Grade 3 or greater adverse events and incidence of treatment discontinuation for reasons other than disease progression.
An earlier study, called BeTa Lung, which evaluated bevacizumab in combination with erlotinib in patients with advanced NSCLC whose disease had progressed following platinum-based CT, failed to meet its primary endpoint of improving OS compared to erlotinib in combination with placebo. However, there was clear evidence of clinical activity, with improvements in the secondary endpoints of PFS and response rate when bevacizumab was added to erlotinib compared to erlotinib alone. An additional trial, called SATURN, showed that erlotinib delayed disease progression when given as a single agent immediately following treatment with CT, compared to placebo. In ATLAS, patients were initially treated with bevacizumab plus CT followed by the addition of erlotinib to bevacizumab in the maintenance phase. Genentech plans to discuss these data with the FDA to determine next steps.
Avastin is currently approved as first-line treatment in combination with carboplatin and paclitaxel for patients with locally-advanced, non-squamous NSCLC, based on a 25 per cent improvement in OS compared to CT alone (hazard ratio=0.80). Tarceva is currently approved as a treatment for patients with advanced NSCLC who have progressed following treatment with at least one prior CT regimen, based on a 37 per cent improvement in OS compared to placebo (hazard ratio=0.73). OSI Pharmaceuticals markets Tarceva through partnerships with Genentech in the US and Roche throughout the rest of the world. Avastin is jointly marketed by Genentech and Roche.
Matthew Dennis - Editor, Cancer Drug News
Pfizer to benefit from Wyeth acquisition
A definitive merger agreement has been entered into under which Pfizer will acquire Wyeth in a cash-and-stock transaction, currently valued at US$50.19 per share, or a total of approximately US$68 billion. The Boards of Directors of both companies have approved the combination, which will create one of the most diversified companies in the global healthcare industry.
Under the terms of the transaction, each outstanding share of Wyeth common stock will be converted into the right to receive US$33.00 in cash and 0.985 of a share of Pfizer common stock, subject to the terms of the merger agreement. Based on the closing price of Pfizer stock as of 23rd January, the stock component is valued at US$17.19 per share. The transaction provides immediate value to Wyeth shareholders through the cash component, as well as continued participation in the future prospects expected to result from the combination through their ownership of approximately 16 per cent of Pfizer’s shares. The transaction will be financed through a combination of cash, debt and stock. A consortium of banks has provided commitments for a total of US$22.5 billion in debt. Pfizer and Wyeth expect the transaction to close at the end of the third quarter or during the fourth quarter 2009.
The new company will be an industry leader in human, animal and consumer health. With the combined biopharmaceuticals business, it will lead in primary and specialty care as well as in small and large molecules. Its geographic presence in most of the world’s developed and developing countries will be unrivalled. Wyeth already has a leadership position in growth areas, such as vaccines, nutritionals and biologics. But what will Pfizer be getting for its money?
In the oncology area, Wyeth currently markets the following products: Torisel (temsirolimus) for the treatment of advanced renal cell carcinoma, and also filed in the EU for mantle cell lymphoma; Neumega (oprelvekin) for the prevention of severe thrombocytopenia and the reduction of the need for platelet transfusions following myelosuppressive chemotherapy in adult patients with non-myeloid malignancies who are at high risk of severe thrombocytopenia; Mylotarg (gemtuzumab ozogamicin) for the treatment of patients with CD33+ acute myeloid leukaemia in first relapse who are 60 years of age or older and who are not considered candidates for other cytotoxic chemotherapy; and Relistor (methylnaltrexone) subcutaneous injection for the treatment of opioid-induced constipation in patients with advanced illness who are receiving palliative care. These will be combined with Pfizer's marketed products, which include Camptosar (irinotecan) for colorectal cancer; Sutent (sunitinib) for gastrointestinal stromal tumours and renal cell carcinoma; and Aromasin (exemestane) for breast cancer.
But what about future products? Wyeth's R&D pipeline includes the following oncology compounds: bosutinib, in Phase III for chronic myelogenous leukaemia and Phase II for breast cancer combination therapy; inotuzumab ozogamicin in Phase III for follicular non-Hodgkin's lymphoma (NHL) and Phase II for diffuse large B-cell lymphoma/NHL; and neratinib (HKI-272), which is in late-stage trials for breast cancer. Although Pfizer has many novel drugs in Phase I and II development, its current Phase III pipeline mainly consists of new indications for sunitinib. The main benefit to come from the acquisition of Wyeth will be Pfizer's increased exposure to areas of the oncology market that it does not currently serve, such as haematological cancers and supportive products.
Matthew Dennis - Editor, Cancer Drug News
Under the terms of the transaction, each outstanding share of Wyeth common stock will be converted into the right to receive US$33.00 in cash and 0.985 of a share of Pfizer common stock, subject to the terms of the merger agreement. Based on the closing price of Pfizer stock as of 23rd January, the stock component is valued at US$17.19 per share. The transaction provides immediate value to Wyeth shareholders through the cash component, as well as continued participation in the future prospects expected to result from the combination through their ownership of approximately 16 per cent of Pfizer’s shares. The transaction will be financed through a combination of cash, debt and stock. A consortium of banks has provided commitments for a total of US$22.5 billion in debt. Pfizer and Wyeth expect the transaction to close at the end of the third quarter or during the fourth quarter 2009.
The new company will be an industry leader in human, animal and consumer health. With the combined biopharmaceuticals business, it will lead in primary and specialty care as well as in small and large molecules. Its geographic presence in most of the world’s developed and developing countries will be unrivalled. Wyeth already has a leadership position in growth areas, such as vaccines, nutritionals and biologics. But what will Pfizer be getting for its money?
In the oncology area, Wyeth currently markets the following products: Torisel (temsirolimus) for the treatment of advanced renal cell carcinoma, and also filed in the EU for mantle cell lymphoma; Neumega (oprelvekin) for the prevention of severe thrombocytopenia and the reduction of the need for platelet transfusions following myelosuppressive chemotherapy in adult patients with non-myeloid malignancies who are at high risk of severe thrombocytopenia; Mylotarg (gemtuzumab ozogamicin) for the treatment of patients with CD33+ acute myeloid leukaemia in first relapse who are 60 years of age or older and who are not considered candidates for other cytotoxic chemotherapy; and Relistor (methylnaltrexone) subcutaneous injection for the treatment of opioid-induced constipation in patients with advanced illness who are receiving palliative care. These will be combined with Pfizer's marketed products, which include Camptosar (irinotecan) for colorectal cancer; Sutent (sunitinib) for gastrointestinal stromal tumours and renal cell carcinoma; and Aromasin (exemestane) for breast cancer.
But what about future products? Wyeth's R&D pipeline includes the following oncology compounds: bosutinib, in Phase III for chronic myelogenous leukaemia and Phase II for breast cancer combination therapy; inotuzumab ozogamicin in Phase III for follicular non-Hodgkin's lymphoma (NHL) and Phase II for diffuse large B-cell lymphoma/NHL; and neratinib (HKI-272), which is in late-stage trials for breast cancer. Although Pfizer has many novel drugs in Phase I and II development, its current Phase III pipeline mainly consists of new indications for sunitinib. The main benefit to come from the acquisition of Wyeth will be Pfizer's increased exposure to areas of the oncology market that it does not currently serve, such as haematological cancers and supportive products.
Matthew Dennis - Editor, Cancer Drug News
Tuesday, January 20, 2009
Europe: drug access still unequal
Four years on from the original study, an update to the Karolinska Report has found that European patients still face unequal access to cancer treatment, depending on where they live. These inequalities and gaps in survival are particularly noticeable when comparing Eastern Europe with Northern and Western Europe. The report by Dr Nils Wilking, a clinical oncologist at the Karolinska Institutet, and Dr Bengt Jönsson, Professor of Health Economics at the Stockholm School of Economics, which is based on findings from the 27 EU countries (excluding Cyprus and Malta), Iceland, Norway and Switzerland, updates and improves on two earlier reports by the same authors in 2005 and 2007. The most recent report was supported by an unrestricted grant from the European Federation of Pharmaceutical Industries and Associations.
The report reveals that whereas cancer incidence is increasing, cancer mortality is decreasing, indicating the positive impact of screening programmes and improvements in treatments. "New treatments have made it possible to target diseases more effectively. For cancer patients, these newer therapies mean an improved quality of life, with less time spent in hospital and the chance to return to their day-to-day activities earlier," stated Wilking.
However the report highlights wide gaps in Europe in relative survival rates. For example, in Sweden 60.3 per cent of men and 61.7 per cent of women diagnosed with cancer survive compared to only 37.7 per cent of men and 49.3 per cent of women in the Czech Republic. EUROCARE 4 data also shows that for a similar incidence, cancer patients in Sweden have greater chances of survival than those in the UK. Healthcare systems in Europe are spending more on cancer, but this expenditure remains lower than the relative burden of cancer in comparison to other diseases.
Patients in Austria, France and Switzerland have the broadest access to newer cancer treatments while Poland, the Czech Republic and the UK continue to lag behind. Jönsson emphasised: "The inequalities, highlighted in our original report in 2005, still remain. For patients and society this is a real concern, as expectations are that all patients in Europe should have equal opportunity to access these treatments, particularly when evidence shows that access to cancer treatment is linked to an improvement in outcome".
The report authors urged policy-makers to take action and proposed new policies to improve treatment access for patients in Europe:
Matthew Dennis - Editor, Cancer Drug News
The report reveals that whereas cancer incidence is increasing, cancer mortality is decreasing, indicating the positive impact of screening programmes and improvements in treatments. "New treatments have made it possible to target diseases more effectively. For cancer patients, these newer therapies mean an improved quality of life, with less time spent in hospital and the chance to return to their day-to-day activities earlier," stated Wilking.
However the report highlights wide gaps in Europe in relative survival rates. For example, in Sweden 60.3 per cent of men and 61.7 per cent of women diagnosed with cancer survive compared to only 37.7 per cent of men and 49.3 per cent of women in the Czech Republic. EUROCARE 4 data also shows that for a similar incidence, cancer patients in Sweden have greater chances of survival than those in the UK. Healthcare systems in Europe are spending more on cancer, but this expenditure remains lower than the relative burden of cancer in comparison to other diseases.
Patients in Austria, France and Switzerland have the broadest access to newer cancer treatments while Poland, the Czech Republic and the UK continue to lag behind. Jönsson emphasised: "The inequalities, highlighted in our original report in 2005, still remain. For patients and society this is a real concern, as expectations are that all patients in Europe should have equal opportunity to access these treatments, particularly when evidence shows that access to cancer treatment is linked to an improvement in outcome".
The report authors urged policy-makers to take action and proposed new policies to improve treatment access for patients in Europe:
- adapt healthcare budgets generally and hospital budgets specifically to incorporate the introduction of new cancer drugs;
- introduce separate funding for cancer drugs, with or without requirements of an additional gathering of data;
- expedite (regulatory and economic) review times for innovative cancer drugs; and
- promote a European collaborative approach to collecting available scientific information for Health Technology Assessments (HTAs).
Matthew Dennis - Editor, Cancer Drug News
Friday, January 16, 2009
Why bladder cancer is deadlier in some
Bladder cancer (BC) is much more likely to be deadly for women and African-Americans, but the reasons long believed to explain the phenomenon account for only part of the differences for such patients compared to their white and male counterparts. These findings, published in the 1st January issue of Cancer (2009;115:68-74), raise a question for doctors and patients: if age, tumour type and stage of the disease upon diagnosis do not account for the increased lethality of the disease in women and African-Americans, then what does?
It is a big question facing researchers in this area where the disease is more lethal in those patients who are less likely to get it. Men are more than three-times as likely as women to develop the disease, and white people are nearly twice as likely to get the disease as African-Americans. Yet, once the disease is present, it is far deadlier in women and African-Americans.
In the new study, scientists at the University of Rochester Medical Center have shown for the first time that the factors traditionally thought to be responsible for the differing course are responsible for only about one-third of the difference between white men and women, and up to two-thirds of the difference between African-Americans and their white counterparts.
To perform the study, researchers analysed the records of 101,249 patients who were diagnosed with BC from 1990 to 2003 as part of the SEER (Surveillance, Epidemiology, and End Results) programme. The team found that in the first year after diagnosis, women were anywhere from approximately 80 to 114 per cent more likely to die from the disease than their male counterparts. That increase was slightly lower in year two, when women were around 52 to 55 per cent more likely to die.
When it came to race, the researchers found that African-Americans were approximately 73 to 103 per cent more likely than their white counterparts to die from the disease within the first two years after diagnosis, and around 40 to 117 per cent more likely to die three or four years after diagnosis. The investigators then examined the data to try to uncover the reasons behind these differences. The team found that the factors traditionally thought to be responsible accounted for only approximately 30 per cent of the difference between the genders among white people, and around 50 to 70 per cent of the differences between the races and genders among African-Americans.
The study's authors speculate about other factors that might be responsible for the differences, though they say that further study is necessary to know for sure. Some of the other issues that might play a role include the choice of treatment, differences among tumours that were not taken into account in the study and access to healthcare. The authors believe that poorer access to healthcare is a clear cause of the higher mortality rates for African-Americans. When it comes to gender, some of the differences are likely to be caused by factors that are not currently understood, such as hormonal differences. But a factor that is known to play a key role is people's reaction when they see blood in their urine. Men are more likely than women to notice blood in their urine, to think it is abnormal, and to report it to doctors and even then, when it is reported, doctors are 65 per cent more likely to refer men than women to urologists.
Matthew Dennis - Editor, Cancer Drug News
It is a big question facing researchers in this area where the disease is more lethal in those patients who are less likely to get it. Men are more than three-times as likely as women to develop the disease, and white people are nearly twice as likely to get the disease as African-Americans. Yet, once the disease is present, it is far deadlier in women and African-Americans.
In the new study, scientists at the University of Rochester Medical Center have shown for the first time that the factors traditionally thought to be responsible for the differing course are responsible for only about one-third of the difference between white men and women, and up to two-thirds of the difference between African-Americans and their white counterparts.
To perform the study, researchers analysed the records of 101,249 patients who were diagnosed with BC from 1990 to 2003 as part of the SEER (Surveillance, Epidemiology, and End Results) programme. The team found that in the first year after diagnosis, women were anywhere from approximately 80 to 114 per cent more likely to die from the disease than their male counterparts. That increase was slightly lower in year two, when women were around 52 to 55 per cent more likely to die.
When it came to race, the researchers found that African-Americans were approximately 73 to 103 per cent more likely than their white counterparts to die from the disease within the first two years after diagnosis, and around 40 to 117 per cent more likely to die three or four years after diagnosis. The investigators then examined the data to try to uncover the reasons behind these differences. The team found that the factors traditionally thought to be responsible accounted for only approximately 30 per cent of the difference between the genders among white people, and around 50 to 70 per cent of the differences between the races and genders among African-Americans.
The study's authors speculate about other factors that might be responsible for the differences, though they say that further study is necessary to know for sure. Some of the other issues that might play a role include the choice of treatment, differences among tumours that were not taken into account in the study and access to healthcare. The authors believe that poorer access to healthcare is a clear cause of the higher mortality rates for African-Americans. When it comes to gender, some of the differences are likely to be caused by factors that are not currently understood, such as hormonal differences. But a factor that is known to play a key role is people's reaction when they see blood in their urine. Men are more likely than women to notice blood in their urine, to think it is abnormal, and to report it to doctors and even then, when it is reported, doctors are 65 per cent more likely to refer men than women to urologists.
Matthew Dennis - Editor, Cancer Drug News
Wednesday, January 7, 2009
2009: the year ahead
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
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
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
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