ImClone Systems' Chairman of the Board, Carl Icahn, has stated that the Special Committee of ImClone's Board of Directors has informed Bristol-Myers Squibb that following the Special Committee's review and discussion, and based upon the advice it received from its advisors, the Special Committee has determined that the unsolicited offer that ImClone received from BMS to acquire ImClone for US$60 per share in cash is inadequate.
Icahn also disclosed that he has had several conversations with the Chief Executive Officer of a large pharmaceutical company. As a result of such conversations, the pharmaceutical company has submitted a proposal, subject to due diligence, but not subject to financing, to acquire ImClone for US$70 per share in cash. Names being bandied about for the unknown bidder include Merck KGaA, Pfizer and GlaxoSmithKline, as well as AstraZeneca and sanofi-aventis. The Special Committee has determined, subject to the execution of a confidentiality agreement, to allow this company to conduct due diligence for a two-week period, subject to extension by mutual consent. No determination has been made as to whether US$70 per share would be adequate.
In response to this disclosure, BMS sent a letter to Icahn stating its disappointment that the offer had been rejected without discussing its merits with BMS and its advisors. BMS also noted that, in contrast to the competing offer, it has made a formal written offer that has been approved by its Board of Directors, is not subject to due diligence and has been fully disclosed to ImClone's stockholders.
BMS currently holds the exclusive long-term marketing rights in the US to Erbitux (cetuximab) and related compounds, including IMC-11F8. BMS stated that it has no intention of agreeing to any modifications to these rights. Additionally, ImClone should understand that BMS’ offer is for the entire company, and any potential restructuring of ImClone could severely jeopardise its value and deprive stockholders of the benefits of the BMS offer.
BMS continues to look forward to engaging directly with ImClone and its financial and legal advisors to discuss the merits of its all-cash offer to acquire the approximately 83 per cent of the company that BMS does not already own. In reply, ImClone submitted a letter to BMS in which it stated that with regard to the assertion concerning rights to IMC-11F8 (which, if ultimately approved for sale, may have a significant competitive effect on Erbitux), ImClone disagrees that BMS' rights are clear and does not waive any rights that ImClone may have with regard thereto. If BMS wishes to make another offer that it believes ImClone would not find inadequate, it is free to do so. Upon receipt of that offer, ImClone will respond appropriately. However, BMS' Chief Financial Officer Jean-Marc Huet has stated that the company is willing to "walk away" from the deal if needed.
Exactly what belongs to whom in the BMS-ImClone partnership will be a key question of interest as ImClone's new mystery bidder conducts its due diligence over the next few weeks. It seems likely that Merck KGaA may be the interested party because it partners with ImClone in selling Erbitux in some countries outside North America and has touted the drug's prospects of being approved for other types of cancer. Perhaps the bidding will now start in earnest?
Matthew Dennis - Editor, Cancer Drug News
Tuesday, September 16, 2008
Telomerase finally gives up its structure
In a landmark study, researchers from the Wistar Institute have deciphered the structure of the active region of telomerase, an enzyme that plays a major role in the development of nearly all cancers. It is hoped that this achievement will open the door to the creation of new, broadly-effective cancer drugs, as well as anti-ageing therapies. The results of the work have been published in the 31st August online edition of Nature (10.1038/nature07283).
Scientists have been searching for over ten years to develop drugs that shut down telomerase, which is considered the best target for the development of new cancer treatments, but they have been hampered in large part by a lack of knowledge of the enzyme's structure. The new findings should help investigators in their efforts to design effective telomerase inhibitors. According to lead study author, Dr Emmanuel Skordalakes, assistant professor in Wistar's Gene Expression and Regulation Program: "Telomerase is an ideal target for chemotherapy because it is active in almost all human tumours, but inactive in most normal cells. That means a drug that deactivates telomerase would likely work against all cancers, with few side effects."
In humans, telomerase adds multiple repeats of a short DNA sequence to the ends of chromosomes, known as telomeres, thus preventing damage and the loss of genetic information during cell division. When telomerase is dormant, telomeres shorten each time a cell divides, eventually leading to genetic instability and cell death. The enzyme is active in cells that multiply frequently, such as embryonic stem cells, but is switched off almost entirely in normal adult cells. Cancer cells, however, often regain the ability to activate telomerase, which has been implicated in 90 per cent of human tumours. The enzyme permits cells to replicate indefinitely and achieve the cellular immortality that is the hallmark of cancer.
Telomerase is a complex structure made up of multiple protein domains and a stretch of RNA, which contains the template the enzyme uses to synthesise telomeres. In 2007, the researchers solved the structure of a key segment of the molecule, the TRBD domain, where RNA binding occurs. However, the complexity of telomerase has proved a roadblock to determining the enzyme's overall architecture, as has the ability to obtain sufficient quantities of the enzyme.
By screening a wide variety of organisms, including protozoa and insects, the scientists discovered that a gene from the red flour beetle could produce telomerase in copious amounts, and a stable form. The researchers used X-ray crystallography, to determine the 3D structure of the enzyme's active region, the catalytic component called telomerase reverse transcriptase protein (TERT). The work revealed surprising features, including the fact that the molecule's three domains are organised into a doughnut shape, an unexpected configuration. Knowledge of the structure allowed the researchers to create a model of the enzyme's function. Looking forward, the scientists plan to further study TERT and search for new telomerase inhibitors that could become cancer therapies, as well as looking at modifying existing drugs. Now telomerase has finally given up its structure, the hard work really starts.
Matthew Dennis - Editor, Cancer Drug News
Scientists have been searching for over ten years to develop drugs that shut down telomerase, which is considered the best target for the development of new cancer treatments, but they have been hampered in large part by a lack of knowledge of the enzyme's structure. The new findings should help investigators in their efforts to design effective telomerase inhibitors. According to lead study author, Dr Emmanuel Skordalakes, assistant professor in Wistar's Gene Expression and Regulation Program: "Telomerase is an ideal target for chemotherapy because it is active in almost all human tumours, but inactive in most normal cells. That means a drug that deactivates telomerase would likely work against all cancers, with few side effects."
In humans, telomerase adds multiple repeats of a short DNA sequence to the ends of chromosomes, known as telomeres, thus preventing damage and the loss of genetic information during cell division. When telomerase is dormant, telomeres shorten each time a cell divides, eventually leading to genetic instability and cell death. The enzyme is active in cells that multiply frequently, such as embryonic stem cells, but is switched off almost entirely in normal adult cells. Cancer cells, however, often regain the ability to activate telomerase, which has been implicated in 90 per cent of human tumours. The enzyme permits cells to replicate indefinitely and achieve the cellular immortality that is the hallmark of cancer.
Telomerase is a complex structure made up of multiple protein domains and a stretch of RNA, which contains the template the enzyme uses to synthesise telomeres. In 2007, the researchers solved the structure of a key segment of the molecule, the TRBD domain, where RNA binding occurs. However, the complexity of telomerase has proved a roadblock to determining the enzyme's overall architecture, as has the ability to obtain sufficient quantities of the enzyme.
By screening a wide variety of organisms, including protozoa and insects, the scientists discovered that a gene from the red flour beetle could produce telomerase in copious amounts, and a stable form. The researchers used X-ray crystallography, to determine the 3D structure of the enzyme's active region, the catalytic component called telomerase reverse transcriptase protein (TERT). The work revealed surprising features, including the fact that the molecule's three domains are organised into a doughnut shape, an unexpected configuration. Knowledge of the structure allowed the researchers to create a model of the enzyme's function. Looking forward, the scientists plan to further study TERT and search for new telomerase inhibitors that could become cancer therapies, as well as looking at modifying existing drugs. Now telomerase has finally given up its structure, the hard work really starts.
Matthew Dennis - Editor, Cancer Drug News
Price may prohibit HPV vaccination in developing world
As vaccinations against human papillomavirus (HPV) begin for girls in another western country, this time in Scotland, questions remain about how best to utilise this technology in other world regions. As discussed at the World Cancer Congress, which was held from 27th to 31st August, in Geneva, Switzerland, the development of highly-effective vaccines against HPV and promising new screening tests provide an unprecedented opportunity to tackle the disease in poor countries, where pap smear screening has largely failed because it is too expensive and too complicated to implement.
At present, approximately 80 per cent of cervical cancer (CC) deaths occur in developing countries, and estimates predict that if current trends continue, these regions will face a 75 per cent increase in the number of cases in the next two decades. Presented at the Congress was the first broad analysis of the cost-effectiveness of introducing HPV vaccination and new screening methods into the hardest hit regions of the world, which include Asia-Pacific, Latin America and the Caribbean. The benefits varied, depending on the size and make-up of the population and the burden of CC in each country.
It was determined that in the Asia-Pacific region, which accounts for more than half of the world's CC cases, vaccination would be cost-effective, even in the poorest countries, if the cost per vaccinated girl was between US$10 and US$25. For Latin America and the Caribbean, the cost per vaccinated girl, including delivery and logistics costs, would have to be less than US$25 to be cost-effective for all countries. In the most developed populations in the region, vaccination would be cost-saving if the cost per vaccinated girl is between US$25 and US$60, and cost-effective at higher prices.
According to Professor Francesc Xavier Bosch of the Catalan Institute of Oncology: "Efforts are needed now to adapt the current price of the vaccines so they meet what individual countries can afford; the solution may be tiered pricing according to gross national income per capita and according to the scale of country effort. Currently the vaccine's price in the private sector is approximately US$120 per dose, or US$360 per vaccinated girl. Many countries will need subsidies for some time."
The price of the vaccine and the support for massive vaccination campaigns is one of the biggest barriers for the moment, but several other challenges lay ahead. Those include generating the political support for an intervention whose pay-off is two or more decades away, cultural acceptability of the vaccine and monitoring the circulating virus. Uncertainties that may affect the success of vaccination programmes include the duration of protection and whether booster shots might be needed, and whether the vaccines will be as effective in girls whose immune systems are suppressed by either malnutrition or other chronic infections, such as HIV or malaria.
For the near future, in developing countries, both vaccination and screening will be needed. However, in the beginning, many countries may have to continue to focus on screening alone until the vaccine becomes more affordable.
Matthew Dennis - Editor, Cancer Drug News
At present, approximately 80 per cent of cervical cancer (CC) deaths occur in developing countries, and estimates predict that if current trends continue, these regions will face a 75 per cent increase in the number of cases in the next two decades. Presented at the Congress was the first broad analysis of the cost-effectiveness of introducing HPV vaccination and new screening methods into the hardest hit regions of the world, which include Asia-Pacific, Latin America and the Caribbean. The benefits varied, depending on the size and make-up of the population and the burden of CC in each country.
It was determined that in the Asia-Pacific region, which accounts for more than half of the world's CC cases, vaccination would be cost-effective, even in the poorest countries, if the cost per vaccinated girl was between US$10 and US$25. For Latin America and the Caribbean, the cost per vaccinated girl, including delivery and logistics costs, would have to be less than US$25 to be cost-effective for all countries. In the most developed populations in the region, vaccination would be cost-saving if the cost per vaccinated girl is between US$25 and US$60, and cost-effective at higher prices.
According to Professor Francesc Xavier Bosch of the Catalan Institute of Oncology: "Efforts are needed now to adapt the current price of the vaccines so they meet what individual countries can afford; the solution may be tiered pricing according to gross national income per capita and according to the scale of country effort. Currently the vaccine's price in the private sector is approximately US$120 per dose, or US$360 per vaccinated girl. Many countries will need subsidies for some time."
The price of the vaccine and the support for massive vaccination campaigns is one of the biggest barriers for the moment, but several other challenges lay ahead. Those include generating the political support for an intervention whose pay-off is two or more decades away, cultural acceptability of the vaccine and monitoring the circulating virus. Uncertainties that may affect the success of vaccination programmes include the duration of protection and whether booster shots might be needed, and whether the vaccines will be as effective in girls whose immune systems are suppressed by either malnutrition or other chronic infections, such as HIV or malaria.
For the near future, in developing countries, both vaccination and screening will be needed. However, in the beginning, many countries may have to continue to focus on screening alone until the vaccine becomes more affordable.
Matthew Dennis - Editor, Cancer Drug News
Wednesday, August 13, 2008
Draft NICE guidance denies RCC drugs
The UK's National Institute for Health and Clinical Excellence (NICE) has issued preliminary recommendations for the treatment of renal cell carcinoma (RCC), concluding that Roche/Genentech's Avastin (bevacizumab), Bayer/Onyx Pharmaceuticals' Nexavar (sorafenib), Pfizer's Sutent (sunitinib) and Wyeth Pharmaceuticals' Torisel (temsirolimus) are not recommended as treatment options for advanced and/or metastatic disease. Although the drugs were shown to be clinically effective and extend life for RCC patients, they were deemed to not be a cost-effective use of NHS resources. NICE is expected to issue final guidance in January 2009.
Following the decision, Cancer Research UK (CRUK) has called for NICE to alter the way that it appraises the value of drugs for rare diseases, such as metastatic RCC, where clinical benefit is proven but evidence is limited due to the small number of available patients. Professor Peter Johnson, CRUK's chief clinician, stated: "We are disappointed at NICE's view that although these drugs are clinically effective, their high price means that they are not considered to be value for money for the NHS. These drugs have shown a small but definite improvement in an illness where there are few alternative treatments. If this decision stands it will be very frustrating for cancer patients and their clinicians."
The charity put forward that possible solutions include looking at the way that pharmaceutical companies are charging the NHS for drugs, and whether appropriate allowances are being made by NICE to compensate for the lack of large-scale trials in these areas. However, it turns out that proposals were submitted by two of the manufacturers relating to drug acquisition costs. But these were not considered by the Department of Health as they had not been agreed before the appraisal.
The preliminary guidance raises questions as to how NICE evaluates cancer drugs, particularly for cancers that only affect a relatively small number of people. The gold-standard method of testing whether a treatment works and is safe is through the use of clinical trials. The larger the number of patients enrolled in a study, and the longer it lasts, the more sure researchers can be about its results. This works for diseases that affect large numbers of people, such as breast and lung cancer, but only around 2,000 people every year are diagnosed with metastatic RCC. Further, only one in ten people diagnosed with this stage of the disease is alive five years later. This means that for relatively rare diseases like this, it can take a long time to conduct large enough studies to gather the evidence needed to gain approval from regulatory agencies.
Even if these studies do demonstrate benefit, as those for the four drugs did, there is still the cost-effectiveness hurdle to overcome. When NICE analysed the data from the trials with its models, it found that the drugs were expensive (around £20,000 to £35,000 per patient per year) compared to the benefit they brought patients. However, concerns have also been raised about these models, which are designed to examine giving drugs to large numbers of people. Are they equally valid for looking at relatively uncommon diseases, such as metastatic RCC? Hopefully NICE will be able to answer these questions when its final guidance is published.
Matthew Dennis - Editor, Cancer Drug News
Following the decision, Cancer Research UK (CRUK) has called for NICE to alter the way that it appraises the value of drugs for rare diseases, such as metastatic RCC, where clinical benefit is proven but evidence is limited due to the small number of available patients. Professor Peter Johnson, CRUK's chief clinician, stated: "We are disappointed at NICE's view that although these drugs are clinically effective, their high price means that they are not considered to be value for money for the NHS. These drugs have shown a small but definite improvement in an illness where there are few alternative treatments. If this decision stands it will be very frustrating for cancer patients and their clinicians."
The charity put forward that possible solutions include looking at the way that pharmaceutical companies are charging the NHS for drugs, and whether appropriate allowances are being made by NICE to compensate for the lack of large-scale trials in these areas. However, it turns out that proposals were submitted by two of the manufacturers relating to drug acquisition costs. But these were not considered by the Department of Health as they had not been agreed before the appraisal.
The preliminary guidance raises questions as to how NICE evaluates cancer drugs, particularly for cancers that only affect a relatively small number of people. The gold-standard method of testing whether a treatment works and is safe is through the use of clinical trials. The larger the number of patients enrolled in a study, and the longer it lasts, the more sure researchers can be about its results. This works for diseases that affect large numbers of people, such as breast and lung cancer, but only around 2,000 people every year are diagnosed with metastatic RCC. Further, only one in ten people diagnosed with this stage of the disease is alive five years later. This means that for relatively rare diseases like this, it can take a long time to conduct large enough studies to gather the evidence needed to gain approval from regulatory agencies.
Even if these studies do demonstrate benefit, as those for the four drugs did, there is still the cost-effectiveness hurdle to overcome. When NICE analysed the data from the trials with its models, it found that the drugs were expensive (around £20,000 to £35,000 per patient per year) compared to the benefit they brought patients. However, concerns have also been raised about these models, which are designed to examine giving drugs to large numbers of people. Are they equally valid for looking at relatively uncommon diseases, such as metastatic RCC? Hopefully NICE will be able to answer these questions when its final guidance is published.
Matthew Dennis - Editor, Cancer Drug News
BMS moves to buy ImClone
Bristol-Myers Squibb has proposed to enter into an agreement to acquire ImClone Systems for US$60.00 per share in cash, or a total payment of approximately US$4.5 billion. BMS currently owns approximately 17 per cent of all outstanding shares of ImClone. BMS' all-cash offer, which is not conditioned on the receipt of financing or on the conduct of due diligence, represents a premium of approximately 30 per cent over ImClone's closing stock price on 30th July, a premium of approximately40 per cent over the average closing price of ImClone's stock during the most recent one-month period and a premium in excess of 40 per cent for the average closing stock prices of ImClone stock during each of the most recent three- and 12-month periods.
James M Cornelius, BMS' Chairman and Chief Executive Officer, stated that the transaction represents an evolutionary development in the companies' seven-year-long relationship. BMS is the natural partner for ImClone as it possesses the knowledge base and resources to advance the company's growth over the long-term, not only with respect toErbitux (cetuximab), which the companies jointly commercialise, but also in terms of developing ImClone's pipeline assets.
ImClone's Board of Directors has formed a committee to study the acquisition offer and to retain advisors to assist it in determining the appropriate course of action. However, the Board's preliminary view is that the offer substantially undervalues the company. ImClone pointed out that its Board has been discussing the possibility of separating the company into its Erbitux and its pipeline businesses in order to maximise the value of the company.
Chairman of ImClone's Board, Carl C Icahn, has stated that he was disturbed that one of the directors on the ImClone Board who is the BMS designee was privy to the information discussed at previous meetings concerning the potential separation of ImClone into two separate components and how this restructuring might enhance stockholder value. Accordingly, the Board is reviewing whether BMS had access to confidential information concerning ImClone and its pipeline. Additionally, Icahn pointed out that ImClone has a pipeline antibody, IMC-11F8, under development which, if ultimately approved for sale, might have a significant competitive effect on Erbitux and that BMS may have no rights to market that product under its agreements with the company.
If BMS gained control of all the Erbitux revenues it would fill a long-term hole caused by the loss of patent protection, starting in 2012 and 2013,surrounding the company's heart disease drug, Plavix (clopidogrel),and antihypertensive, Avapro (irbesartan). Erbitux is indicated for use in the treatment of patients with metastatic colorectal cancer and in the treatment of squamous cell carcinoma of the head and neck. Under the agreement between BMS and ImClone, which expires in September2018, ImClone receives a distribution fee based on a flat rate of 39 per cent of Erbitux net sales in North America. This agreement was amended in July 2007 to provide for additional development funding for certain indications.
Merck KGaA is also a partner in the co-development and co-commercialisation of Erbitux in Japan and other markets outside of the US. As such, it could perhaps emerge as the most likely competitor for ImClone. It would make sense for Merck to protect its investment in the drug, since it was the company's own clinical trial that finally persuaded the FDA to approve Erbitux, and a new Merck trial has shown it to be efective in fighting lung cancer as well.
Matthew Dennis - Editor, Cancer Drug News
James M Cornelius, BMS' Chairman and Chief Executive Officer, stated that the transaction represents an evolutionary development in the companies' seven-year-long relationship. BMS is the natural partner for ImClone as it possesses the knowledge base and resources to advance the company's growth over the long-term, not only with respect toErbitux (cetuximab), which the companies jointly commercialise, but also in terms of developing ImClone's pipeline assets.
ImClone's Board of Directors has formed a committee to study the acquisition offer and to retain advisors to assist it in determining the appropriate course of action. However, the Board's preliminary view is that the offer substantially undervalues the company. ImClone pointed out that its Board has been discussing the possibility of separating the company into its Erbitux and its pipeline businesses in order to maximise the value of the company.
Chairman of ImClone's Board, Carl C Icahn, has stated that he was disturbed that one of the directors on the ImClone Board who is the BMS designee was privy to the information discussed at previous meetings concerning the potential separation of ImClone into two separate components and how this restructuring might enhance stockholder value. Accordingly, the Board is reviewing whether BMS had access to confidential information concerning ImClone and its pipeline. Additionally, Icahn pointed out that ImClone has a pipeline antibody, IMC-11F8, under development which, if ultimately approved for sale, might have a significant competitive effect on Erbitux and that BMS may have no rights to market that product under its agreements with the company.
If BMS gained control of all the Erbitux revenues it would fill a long-term hole caused by the loss of patent protection, starting in 2012 and 2013,surrounding the company's heart disease drug, Plavix (clopidogrel),and antihypertensive, Avapro (irbesartan). Erbitux is indicated for use in the treatment of patients with metastatic colorectal cancer and in the treatment of squamous cell carcinoma of the head and neck. Under the agreement between BMS and ImClone, which expires in September2018, ImClone receives a distribution fee based on a flat rate of 39 per cent of Erbitux net sales in North America. This agreement was amended in July 2007 to provide for additional development funding for certain indications.
Merck KGaA is also a partner in the co-development and co-commercialisation of Erbitux in Japan and other markets outside of the US. As such, it could perhaps emerge as the most likely competitor for ImClone. It would make sense for Merck to protect its investment in the drug, since it was the company's own clinical trial that finally persuaded the FDA to approve Erbitux, and a new Merck trial has shown it to be efective in fighting lung cancer as well.
Matthew Dennis - Editor, Cancer Drug News
Review confirms Gardasil's safety; predicted sales hit
Based on the review of available information, the FDA and the Centers for Disease Control and Prevention (CDC) have reaffirmed that Gardasil (quadrivalent human papillomavirus [HPV] types 6, 11, 16, 18 recombinant vaccine) continues to be safe and effective, and its benefits continue to outweigh its risks.
To date, the manufacturer, Merck & Co has distributed over 16 million doses of Gardasil in the US and as of 30th June, there have been 9,749 reports of adverse events following vaccination. Of these, 94 per cent were classified as reports of non-serious events, and 6 per cent as serious events. The non-serious events include syncope, pain at the injection site, headache, nausea and fever.
However, concerns have been raised about reports of deaths occurring in individuals after receiving Gardasil. As of 30th June, 20 deaths had been reported, although there was not a common pattern that would suggest they were caused by the vaccine. According to the review, in cases where autopsy, death certificate and medical records were available, the cause of death was explained by factors other than the vaccine.
Guillain-Barré syndrome (GBS) has also been reported in individuals following vaccination with Gardasil. The FDA and CDC have reviewed the reports and, to date, there is no evidence that Gardasil has increased the rate of GBS above that expected in the population. Thromboembolic disorders have also been reported in people who have received Gardasil. Most of these individuals had risk factors for blood clots, such as use of oral contraceptives, which are known to increase the risk of clotting. Thromboembolic disorders as well as other medical events are being studied through the Vaccine Safety Datalink Project in previously-planned, controlled studies. Merck has also committed to conduct a large post-marketing study to further assess the vaccine's safety.
The vaccine is one of Merck's flagship products but its sales have been under pressure. The company has recently predicted 2008 Gardasil sales of between US$1.4 billion and US$1.6 billion, down from prior estimates of US$1.9 billion to US$2.1 billion. The lower forecast is due, in part, to Merck's failure earlier in the year to receive US approval to market the vaccine to older women aged 27 to 45 years, as well as to extend its indication to include HPV types not included in the vaccine.
Gardasil is approved in the US for use in girls and women aged nine through 26 years to prevents infection with the types of HPV that cause most cases of cervical cancer and genital warts. The CDC's Advisory Committee on Immunization Practices recommended routine three-dose vaccination of girls aged 11 and 12 years. The vaccine is also recommended for girls and women aged 13 through 26 years who have not yet been vaccinated or who have not received all three doses.
Gardasil is marketed by sanofi pasteur MSD (sanofi-aventis’ joint venture [JV] with Merck) in EU countries covered by the JV and several other European countries. In the remaining European countries, located in Central and Eastern Europe, the vaccine is marketed by Merck Sharp & Dohme under the tradename, Silgard.
Matthew Dennis - Editor, Cancer Drug News
To date, the manufacturer, Merck & Co has distributed over 16 million doses of Gardasil in the US and as of 30th June, there have been 9,749 reports of adverse events following vaccination. Of these, 94 per cent were classified as reports of non-serious events, and 6 per cent as serious events. The non-serious events include syncope, pain at the injection site, headache, nausea and fever.
However, concerns have been raised about reports of deaths occurring in individuals after receiving Gardasil. As of 30th June, 20 deaths had been reported, although there was not a common pattern that would suggest they were caused by the vaccine. According to the review, in cases where autopsy, death certificate and medical records were available, the cause of death was explained by factors other than the vaccine.
Guillain-Barré syndrome (GBS) has also been reported in individuals following vaccination with Gardasil. The FDA and CDC have reviewed the reports and, to date, there is no evidence that Gardasil has increased the rate of GBS above that expected in the population. Thromboembolic disorders have also been reported in people who have received Gardasil. Most of these individuals had risk factors for blood clots, such as use of oral contraceptives, which are known to increase the risk of clotting. Thromboembolic disorders as well as other medical events are being studied through the Vaccine Safety Datalink Project in previously-planned, controlled studies. Merck has also committed to conduct a large post-marketing study to further assess the vaccine's safety.
The vaccine is one of Merck's flagship products but its sales have been under pressure. The company has recently predicted 2008 Gardasil sales of between US$1.4 billion and US$1.6 billion, down from prior estimates of US$1.9 billion to US$2.1 billion. The lower forecast is due, in part, to Merck's failure earlier in the year to receive US approval to market the vaccine to older women aged 27 to 45 years, as well as to extend its indication to include HPV types not included in the vaccine.
Gardasil is approved in the US for use in girls and women aged nine through 26 years to prevents infection with the types of HPV that cause most cases of cervical cancer and genital warts. The CDC's Advisory Committee on Immunization Practices recommended routine three-dose vaccination of girls aged 11 and 12 years. The vaccine is also recommended for girls and women aged 13 through 26 years who have not yet been vaccinated or who have not received all three doses.
Gardasil is marketed by sanofi pasteur MSD (sanofi-aventis’ joint venture [JV] with Merck) in EU countries covered by the JV and several other European countries. In the remaining European countries, located in Central and Eastern Europe, the vaccine is marketed by Merck Sharp & Dohme under the tradename, Silgard.
Matthew Dennis - Editor, Cancer Drug News
Roche looks to buy Genentech
Roche has 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 to equity holders of Genentech other than Roche. Roche acquired a majority stake in Genentech in 1990 and currently owns 55.9 per cent of all outstanding shares.
The offer represents 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 predict that the move undervalues the company and Genentech will refuse the initial offer, pricing the company higher at between US$100.00 and US$120.00 per share.
If the deal does go through then it would be the biggest in the sector since Pfizer paid US$57 billion for Pharmacia five years ago. The pharmaceutical sector is witnessing a spate of acquisitions of biotech companies as groups search for new drugs, especially in oncology, to offset the decline in their product pipelines.
Under the proposed acquisition, Genentech will operate as an independent research and early development centre within Roche from its existing campus in South San Francisco, CA, retaining its expertise and approach to discovering and progressing new molecules. The structure of the combined company will allow for a diversity of approaches in research and early development, while also strengthening cross fertilisation between the companies, leading to enhanced overall innovation within the Group. Roche's recently-adopted Disease Biology Area approach, which allows five diverse groups to manage their innovative portfolios, will be maintained and strengthened. This, together with recent moves into RNAi and delivery technologies, as well as licensing activities, continues to provide a stimulating environment for the creation of medically-differentiated medicines.
Roche's Pharma commercial operations in the US will be moved from Nutley to Genentech's site in South San Francisco, CA. The existing US sales organisations of both companies will be maintained, resulting in a very strong presence in several specialty areas. The combined entity will be the seventh largest US pharmaceuticals company in terms of market share. It will generate more than US$15 billion in annual revenues and will employ around 17,500 pharma employees in the US alone, including a combined sales force of approximately 3,000 people. Including diagnostics, the Roche Group will employ around 25,000 people in the US.
With various clinical trial results expected in the next 18 months, analysts expect that Genentech's share price could soar on the back of positive data. Genentech's Avastin (bevacizumab) is in clinical testing as a secondary treatment for colon and breast cancer, and Rituxan (rituximab) is being investigated as a possible lupus treatment. Some experts believe that positive outcomes could bring Genentech an additional US$5 billion in peak sales for Avastin alone. The ultimate goal, however, would be to pair Genentech's therapeutics with Roche’s diagnostics to inform physicians which patients can benefit from specific treatments. The move looks like a smart one for both parties.
Matthew Dennis - Editor, Cancer Drug News
The offer represents 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 predict that the move undervalues the company and Genentech will refuse the initial offer, pricing the company higher at between US$100.00 and US$120.00 per share.
If the deal does go through then it would be the biggest in the sector since Pfizer paid US$57 billion for Pharmacia five years ago. The pharmaceutical sector is witnessing a spate of acquisitions of biotech companies as groups search for new drugs, especially in oncology, to offset the decline in their product pipelines.
Under the proposed acquisition, Genentech will operate as an independent research and early development centre within Roche from its existing campus in South San Francisco, CA, retaining its expertise and approach to discovering and progressing new molecules. The structure of the combined company will allow for a diversity of approaches in research and early development, while also strengthening cross fertilisation between the companies, leading to enhanced overall innovation within the Group. Roche's recently-adopted Disease Biology Area approach, which allows five diverse groups to manage their innovative portfolios, will be maintained and strengthened. This, together with recent moves into RNAi and delivery technologies, as well as licensing activities, continues to provide a stimulating environment for the creation of medically-differentiated medicines.
Roche's Pharma commercial operations in the US will be moved from Nutley to Genentech's site in South San Francisco, CA. The existing US sales organisations of both companies will be maintained, resulting in a very strong presence in several specialty areas. The combined entity will be the seventh largest US pharmaceuticals company in terms of market share. It will generate more than US$15 billion in annual revenues and will employ around 17,500 pharma employees in the US alone, including a combined sales force of approximately 3,000 people. Including diagnostics, the Roche Group will employ around 25,000 people in the US.
With various clinical trial results expected in the next 18 months, analysts expect that Genentech's share price could soar on the back of positive data. Genentech's Avastin (bevacizumab) is in clinical testing as a secondary treatment for colon and breast cancer, and Rituxan (rituximab) is being investigated as a possible lupus treatment. Some experts believe that positive outcomes could bring Genentech an additional US$5 billion in peak sales for Avastin alone. The ultimate goal, however, would be to pair Genentech's therapeutics with Roche’s diagnostics to inform physicians which patients can benefit from specific treatments. The move looks like a smart one for both parties.
Matthew Dennis - Editor, Cancer Drug News
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