An analysis of the adverse events (AEs) reported following distribution of Merck & Co's quadrivalent human papillomavirus (qHPV) recombinant vaccine, Gardasil, since 2006, has indicated that AE rates were consistent with prelicensing data and expected background rates of other vaccines, with the exception of a higher proportion of reports of fainting and blood clots.
Gardasil is the world's first cervical cancer vaccine, which can also help to prevent vulvar and vaginal cancers and genital warts caused by HPV types 6, 11, 16 and 18. In June 2006, the FDA licensed Gardasil for females aged nine to 26 years to prevent infection with genital HPV. Shortly after that, the Advisory Committee on Immunization Practices recommended routine vaccination of females aged 11 to 12 years with three doses of qHPV and catch-up vaccination for females aged 13 to 26 years.
In the new study, published in the 19th August issue of JAMA (2009;302:750-757), the researchers analysed reports of AEs following qHPV immunisation received by the Vaccine Adverse Event Reporting System (VAERS) from 1st June 2006 until 31st December 2008. Additional analyses were performed for some AEs following immunisations (AEFIs) in prelicensure trials, those of unusual severity or those that had received public attention.
During the study period, VAERS received 12,424 reports of AEFIs following receipt of qHPV, an overall reporting rate of 53.9 reports per 100,000 vaccine doses distributed. Of the 8,247 reports that included onset interval, 4,393 (40 per cent) occurred on the day of vaccination. Among 9,396 reports (77 per cent) with dose information, 5,772 (61 per cent) followed the first dose, 2,380 (25 per cent) followed the second dose and 1,183 (13 per cent) followed the third dose of qHPV.
Among the 12,424 AEFI reports, 772 (6.2 per cent) were serious, including 32 reports of death. The reporting rates per 100,000 qHPV doses distributed were: 8.2 for syncope; 7.5 for local site reactions; 6.8 for dizziness; 5.0 for nausea; 4.1 for headache; 3.1 for hypersensitivity reactions; 2.6 for urticaria; 0.2 for venous thromboembolic events, autoimmune disorders and Guillain-Barré syndrome; and 0.1 for anaphylaxis and death. Analysis indicated a disproportional reporting of fainting and blood clot events.
The VAERS database that was the primary source for the study is one of the many mechanisms used to assess the safety of vaccines. Merck also monitors vaccine safety by conducting comprehensive analyses of AEs reported to the company and shares these analyses with the Centers for Disease Control and Prevention (CDC), the FDA, and regulatory and medical authorities around the world to support their efforts. After carefully reviewing all of the information available to Merck about reported AEs, including the findings in the discussed study, the company continues to be confident in the safety profile of Gardasil. While no vaccine or medicine is completely without risk, leading health organisations throughout the world, including the CDC and EMEA, have reviewed the available safety and efficacy information about Gardasil and continue to recommend its use.
Richard M Haupt, head of the Gardasil clinical programme commented: "we will continue our practice of effectively communicating the safety profile of Gardasil, it's a responsibility Merck takes very seriously...Parents should understand the extensive data supporting the safety profile of this vaccine, and we encourage them to look to CDC and FDA, and to the advice of their own physicians, to make an informed choice about something as important as a vaccine to help prevent cervical cancer".
Alice Rossiter Cancer Drug News Editor
Showing posts with label Merck and Co. Show all posts
Showing posts with label Merck and Co. Show all posts
Wednesday, August 26, 2009
Thursday, June 4, 2009
Early collaboration: a sign of the times?
Touted as a first-of-its-kind deal, Merck & Co and AstraZeneca have teamed up to research a novel combination anticancer regimen composed of two investigational compounds, MK-2206 and AZD6244 (ARRY-886). The collaboration, which is unusual as it involves two drugs so far from approval, will investigate the agents in a Phase I safety and tolerability trial.
Most combination regimens are investigated once the compounds have either progressed to late-stage development or are already commercially available. This new agreement breaks from that mould as the companies appear to have overcome many of the sticking points that have previously prevented this type of interaction between big pharma. The reason that few development agreements between large companies are signed is that they are extremely complicated. Issues concerning control, valuation and overlap with other projects all present hurdles. Then there is the question of working with your competitor, something that is not encouraged.
But it appears that this deal was struck not because the companies were actively seeking such collaboration, rather a chance encounter at an airport in November 2007 led to it happening. Reports suggest that two scientists, one from Merck and the other from AstraZeneca, got talking at airport security about their respective programmes and the rationale for combining them.
Merck's MK-2206 is the most advanced AKT inhibitor in development. AKT acts downstream of PI3K in the PI3K/PTEN/AKT signalling pathway. AstraZeneca's AZD6244 targets MEK, which plays an important role in a parallel signalling pathway. Laboratory evidence has suggested that the two compounds given in combination could have a much more potent affect against tumours than each agent separately. Even though AstraZencea was also working on its own AKT inhibitor and Merck was developing a drug to block MEK, the companies determined that collaborating would offer a quicker route to market.
So, how will the partnership progress? The companies have agreed to jointly fund a Phase I trial, after which they will consider further clinical development. If the two companies wish to eventually develop a fixed-dose combination then they may have to expand their relationship to possibly include multiple compounds or entire pathways. It could be that an initial goal would be to have each company move a drug through development to market with an approved label supporting use of the other agent in combination. Indeed, if this deal works, then it may pave the way for future similar collaborations.
Sadly, this will be my last issue as Editor of Cancer Drug News as I am moving on to pursue new challenges within the pharma news industry. I hope that you have found the service a valuable information source and I am sure that the new Editor, Alice Rossiter, will continue to uphold the standards of coverage that you as a reader are used to.
Matthew Dennis - Editor, Cancer Drug News
Most combination regimens are investigated once the compounds have either progressed to late-stage development or are already commercially available. This new agreement breaks from that mould as the companies appear to have overcome many of the sticking points that have previously prevented this type of interaction between big pharma. The reason that few development agreements between large companies are signed is that they are extremely complicated. Issues concerning control, valuation and overlap with other projects all present hurdles. Then there is the question of working with your competitor, something that is not encouraged.
But it appears that this deal was struck not because the companies were actively seeking such collaboration, rather a chance encounter at an airport in November 2007 led to it happening. Reports suggest that two scientists, one from Merck and the other from AstraZeneca, got talking at airport security about their respective programmes and the rationale for combining them.
Merck's MK-2206 is the most advanced AKT inhibitor in development. AKT acts downstream of PI3K in the PI3K/PTEN/AKT signalling pathway. AstraZeneca's AZD6244 targets MEK, which plays an important role in a parallel signalling pathway. Laboratory evidence has suggested that the two compounds given in combination could have a much more potent affect against tumours than each agent separately. Even though AstraZencea was also working on its own AKT inhibitor and Merck was developing a drug to block MEK, the companies determined that collaborating would offer a quicker route to market.
So, how will the partnership progress? The companies have agreed to jointly fund a Phase I trial, after which they will consider further clinical development. If the two companies wish to eventually develop a fixed-dose combination then they may have to expand their relationship to possibly include multiple compounds or entire pathways. It could be that an initial goal would be to have each company move a drug through development to market with an approved label supporting use of the other agent in combination. Indeed, if this deal works, then it may pave the way for future similar collaborations.
Sadly, this will be my last issue as Editor of Cancer Drug News as I am moving on to pursue new challenges within the pharma news industry. I hope that you have found the service a valuable information source and I am sure that the new Editor, Alice Rossiter, will continue to uphold the standards of coverage that you as a reader are used to.
Matthew Dennis - Editor, Cancer Drug News
Tuesday, May 12, 2009
Cervarix on top in head-to-head, but how meaningful?
The first comparative study of the two licensed human papillomavirus (HPV) vaccines, Cervarix and Gardasil (HPV types 6, 11, 16, 18 recombinant vaccine), has shown that the former generated a significantly higher immune response as measured by neutralising antibodies (Abs) and memory B-cells.
Although GlaxoSmithKline has touted these results as highly positive, others have hit back claiming that the trial is meaningless as it did not look at which vaccine was more effective at preventing actual cases of cervical cancer or precancerous lesions. This would require a longer and larger trial, which GSK has said it has no plans to conduct. Instead, the company hopes that the head-to-head study will boost the profile of Cervarix, which is yet to be launched in the US and is trailing Sanofi Pasteur MSD's (sanofi-aventis and Merck & Co joint venture) Gardasil in global markets.
Meanwhile, recent data on Gardasil have shown that the vaccine offers protection from certain HPV strains for up to 9.5 years; previously, data only showed its effects for five years. In another study, Gardasil reduced the number of abnormal Pap tests and cervical procedures. However, with Gardasil's US sales falling and Cervarix not even on the market yet in that territory, can the comparative trial data make a difference in revenues for GSK?
Gardasil, which was first to market, and launched in the US and Europe in 2006, generated sales of US$1.4 billion in 2008, while Cervarix brought in just US$231 million. Cervarix is still awaiting US marketing approval, and has only been adopted as the vaccine in national immunisation programmes for two European countries, the UK and the Netherlands. The FDA refused to approve Cervarix until GSK provided more clinical information, but the company expects approval to come later this year.
So what of the new comparative data? The presence of Abs is a first indication of the body's ability to protect itself against disease, but this does not necessarily mean Cervarix could prevent more infections than Gardasil. The study showed that Cervarix provided significantly higher neutralising Ab levels than Gardasil: more than two-times higher for HPV type 16 and more than six-times higher for HPV 18. For both virus strains, Cervarix also induced 2.7-times more memory B-cells, another important element of the immune system.
According to GSK, the study "offers the first evidence that these two vaccines do not generate the same immune response against HPV types 16 and 18, the two most common cancer-causing virus types". Its competitor was dismissive of the data, with Bennett Lee, Medical Director for Gardasil at Sanofi Pasteur MSD commenting: "We see no clinical relevance in the results of this study ... and we don't see the point of doing such a comparison. If you want to compare vaccines, you compare clinical efficacy". However, the final word will come from doctors and patients when, and if, Cervarix is licensed in the US later this year.
Matthew Dennis - Editor, Cancer Drug News
Although GlaxoSmithKline has touted these results as highly positive, others have hit back claiming that the trial is meaningless as it did not look at which vaccine was more effective at preventing actual cases of cervical cancer or precancerous lesions. This would require a longer and larger trial, which GSK has said it has no plans to conduct. Instead, the company hopes that the head-to-head study will boost the profile of Cervarix, which is yet to be launched in the US and is trailing Sanofi Pasteur MSD's (sanofi-aventis and Merck & Co joint venture) Gardasil in global markets.
Meanwhile, recent data on Gardasil have shown that the vaccine offers protection from certain HPV strains for up to 9.5 years; previously, data only showed its effects for five years. In another study, Gardasil reduced the number of abnormal Pap tests and cervical procedures. However, with Gardasil's US sales falling and Cervarix not even on the market yet in that territory, can the comparative trial data make a difference in revenues for GSK?
Gardasil, which was first to market, and launched in the US and Europe in 2006, generated sales of US$1.4 billion in 2008, while Cervarix brought in just US$231 million. Cervarix is still awaiting US marketing approval, and has only been adopted as the vaccine in national immunisation programmes for two European countries, the UK and the Netherlands. The FDA refused to approve Cervarix until GSK provided more clinical information, but the company expects approval to come later this year.
So what of the new comparative data? The presence of Abs is a first indication of the body's ability to protect itself against disease, but this does not necessarily mean Cervarix could prevent more infections than Gardasil. The study showed that Cervarix provided significantly higher neutralising Ab levels than Gardasil: more than two-times higher for HPV type 16 and more than six-times higher for HPV 18. For both virus strains, Cervarix also induced 2.7-times more memory B-cells, another important element of the immune system.
According to GSK, the study "offers the first evidence that these two vaccines do not generate the same immune response against HPV types 16 and 18, the two most common cancer-causing virus types". Its competitor was dismissive of the data, with Bennett Lee, Medical Director for Gardasil at Sanofi Pasteur MSD commenting: "We see no clinical relevance in the results of this study ... and we don't see the point of doing such a comparison. If you want to compare vaccines, you compare clinical efficacy". However, the final word will come from doctors and patients when, and if, Cervarix is licensed in the US later this year.
Matthew Dennis - Editor, Cancer Drug News
Friday, March 13, 2009
Merck to pay US$41.1 billion for Schering-Plough
A definitive merger agreement has been unanimously approved by the Boards of Directors under which Merck & Co and Schering-Plough will combine, under the name Merck, in a stock and cash transaction. Under the terms of the agreement, Schering-Plough shareholders will receive 0.5767 shares and US$10.50 in cash for each share of Schering-Plough. Each Merck share will automatically become a share of the combined company.
Based on the closing price of Merck stock on 6th March, the consideration to be received by Schering-Plough shareholders is valued at US$23.61 per share, or US$41.1 billion in the aggregate. This price represents a premium to Schering-Plough shareholders of approximately 34 per cent based on the closing price of Schering-Plough stock on 6th March. The consideration also represents a premium of approximately 44 per cent based on the average closing price of the two stocks over the last 30 trading days.
Upon closing of the transaction, Merck shareholders are expected to own approximately 68 per cent of the combined company and Schering-Plough shareholders are expected to own approximately 32 per cent. Merck anticipates that the transaction will be modestly accretive to non-GAAP EPS in the first full year following completion and significantly accretive thereafter.
The combination significantly broadens Merck's portfolio of medicines driven, in part, by the addition of valuable products with long periods of exclusivity. By leveraging the combined company's expanded product offerings, Merck expects to benefit from additional revenue growth opportunities. For example, the combined company will have expanded opportunities for life-cycle management through the introduction of potential new combinations and formulations of existing products. In addition, Merck and Schering-Plough together have high-potential early-, mid- and late-stage pipeline candidates. The transaction will double the number of potential medicines Merck has in Phase III development, bringing the total to 18. The combined company will have a more diverse portfolio across important therapeutic areas, including oncology.
Schering-Plough's current oncology products, which include Caelyx (pegylated liposomal doxorubicin), Intron A (interferon alpha-2b recombinant for injection)/PegIntron (peginterferon alpha-2b) and Temodar/Temodal (temozolomide) Capsules, will enable Merck to expand its presence in this area and provide the necessary foundation to take advantage of the combined company's promising pipeline. Merck also expects to benefit from a solid portfolio of women's health products, which includes the cervical cancer vaccine, Gardasil (human papillomavirus quadrivalent types 6, 11, 16 and 18 vaccine, recombinant).
The transaction is subject to approval by Merck and Schering-Plough shareholders, and the satisfaction of customary closing conditions and regulatory approvals, including expiration or termination of the applicable waiting period under the Hart-Scott-Rodino Act, as well as clearance by the EC under the EC Merger Regulation and certain other foreign jurisdictions. Merck and Schering-Plough expect to complete the transaction in the fourth quarter of 2009, by which time there may well have been more such acquisitions, with Bristol-Myers Squibb being the current favourite target.
Matthew Dennis - Editor, Cancer Drug News
Based on the closing price of Merck stock on 6th March, the consideration to be received by Schering-Plough shareholders is valued at US$23.61 per share, or US$41.1 billion in the aggregate. This price represents a premium to Schering-Plough shareholders of approximately 34 per cent based on the closing price of Schering-Plough stock on 6th March. The consideration also represents a premium of approximately 44 per cent based on the average closing price of the two stocks over the last 30 trading days.
Upon closing of the transaction, Merck shareholders are expected to own approximately 68 per cent of the combined company and Schering-Plough shareholders are expected to own approximately 32 per cent. Merck anticipates that the transaction will be modestly accretive to non-GAAP EPS in the first full year following completion and significantly accretive thereafter.
The combination significantly broadens Merck's portfolio of medicines driven, in part, by the addition of valuable products with long periods of exclusivity. By leveraging the combined company's expanded product offerings, Merck expects to benefit from additional revenue growth opportunities. For example, the combined company will have expanded opportunities for life-cycle management through the introduction of potential new combinations and formulations of existing products. In addition, Merck and Schering-Plough together have high-potential early-, mid- and late-stage pipeline candidates. The transaction will double the number of potential medicines Merck has in Phase III development, bringing the total to 18. The combined company will have a more diverse portfolio across important therapeutic areas, including oncology.
Schering-Plough's current oncology products, which include Caelyx (pegylated liposomal doxorubicin), Intron A (interferon alpha-2b recombinant for injection)/PegIntron (peginterferon alpha-2b) and Temodar/Temodal (temozolomide) Capsules, will enable Merck to expand its presence in this area and provide the necessary foundation to take advantage of the combined company's promising pipeline. Merck also expects to benefit from a solid portfolio of women's health products, which includes the cervical cancer vaccine, Gardasil (human papillomavirus quadrivalent types 6, 11, 16 and 18 vaccine, recombinant).
The transaction is subject to approval by Merck and Schering-Plough shareholders, and the satisfaction of customary closing conditions and regulatory approvals, including expiration or termination of the applicable waiting period under the Hart-Scott-Rodino Act, as well as clearance by the EC under the EC Merger Regulation and certain other foreign jurisdictions. Merck and Schering-Plough expect to complete the transaction in the fourth quarter of 2009, by which time there may well have been more such acquisitions, with Bristol-Myers Squibb being the current favourite target.
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
Wednesday, August 13, 2008
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
Thursday, June 19, 2008
UK chooses Cervarix over Gardasil
The Department of Health (DoH), UK, has awarded the contract to provide the vaccine against human papillomavirus (HPV) to GlaxoSmithKline for its product, Cervarix. The contract is to supply the vaccine that protects against cervical cancer (CC) and precancerous cell changes in the cervix caused by HPV. The vaccine will guard against the two HPV strains that cause 70 per cent of cases of CC, types 16 and 18. The vaccine will be made available to girls aged 12 to 13 years from September, while a year later it will also be administered to girls up to 18 years of age in a two-year, catch-up programme.
GSK's CC vaccine is approved in 64 countries worldwide, but this was the first major national tender for which the company had bid. According to Eddie Gray, President of Pharmaceuticals Europe for GSK: "This is great news for girls and women across the UK and reflects the growing confidence in Cervarix, which provides cervical cancer protection with a strong and sustained immune response."
The UK's Joint Committee on Vaccination and Immunisation, which provides independent expert advice to ministers on vaccination, examined a wide range of evidence before recommending in June 2007 that an HPV vaccination programme be routinely introduced for 12 to 13 year old girls. However, this left the DoH to choose between Cervarix and its competitor, sanofi pasteur MSD's (sanofi-aventis and Merck & Co joint venture) Gardasil (quadrivalent HPV types 6, 11, 16, 18, recombinant vaccine), which are both licensed in the EU.
An adjudication was carried out to examine the vaccines offered against a wide range of criteria, such as their scientific qualities and cost effectiveness. The criteria used for the adjudication had been shared in advance with the companies which tendered. Following this process, the DoH selected Cervarix, going against the decision of many EU countries who have opted for Gardasil and the wider protection it offers. Commenting on this, Dr Nicholas Kitchin, UK Medical Director, sanofi pasteur MSD, stated: "We regret that school girls in the UK, unlike most of their peers in Western Europe, the USA, Australia, New Zealand and Canada, will not benefit from the unmatched cervical cancer protection and additional benefits provided by the world's leading HPV vaccine, Gardasil."
Cervarix uses GSK's proprietary AS04 adjuvant as its main differentiating point, which may enhance the immunogenicity of the vaccine, therefore potentially reducing the need for booster shots. However, the long-term efficacy of the two vaccines is believed to be similar.
The key reason for the DoH choosing Cervarix is likely to be price. With a list price for a full course of Gardasil as high as US$375 per person in the US, HPV vaccine costs are a key issue. Although the cost of Cervarix is commercially confidential, it can presently be administered through private clinics at a cost of £130.00 per injection (the immunisation course consists of three injections). GSK may have offered a heavily discounted price, relative to Gardasil, making the DoH’s decision easier. Another factor that must not be forgotten is the fact that GSK is, after all, a British company.
Matthew Dennis - Editor, Cancer Drug News
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