The EMEA's CHMP has issued a positive opinion supporting the approval of AstraZeneca's targeted oral anticancer drug, Iressa (gefitinib), for the treatment of non-small cell lung cancer (NSCLC). Specifically, the CHMP has recommended approval of Iressa for adults with locally-advanced or metastatic NSCLC with activating mutations of EGFr-tyrosine kinase, in all lines of therapy. However, AstraZeneca will be required to conduct a follow-up measure study to generate further data in a Caucasian NSCLC patient population. The company is in discussion with the CHMP to finalise the study design and endpoints.
The opinion was based on a submission package including two pivotal Phase III studies, IPASS (IRESSA Pan-ASia Study) and INTEREST (IRESSA Non-small-cell lung cancer Trial Evaluating REsponse and Survival against Taxotere). The IPASS trial exceeded its primary objective, demonstrating superior progression-free survival (PFS), greater objective response rate (ORR), improved tolerability and significant quality-of-life benefits for Iressa, compared to carboplatin+paclitaxel doublet chemotherapy (CT) in clinically-selected first-line patients in Asia. However, the treatment effect was not constant over time, with the probability of being progression-free in favour of carboplatin+paclitaxel in the first six months and in favour of Iressa in the following 16 months. This was likely due to the different effect of Iressa in subgroups defined by EGFr tumour mutation status. PFS was significantly longer for Iressa than doublet CT in patients with EGFr mutation-positive tumours, and significantly longer for doublet CT than Iressa in patients with EGFr mutation-negative tumours.
The INTEREST study met its primary objective, demonstrating equivalent overall survival (OS) and significant quality-of-life benefits for Iressa, compared to standard CT (docetaxel) in the pretreated setting. Preplanned subgroup analyses showed a significant improvement in PFS and ORR for Iressa over docetaxel in patients with EGFr mutation-positive tumours.
In 2005, AstraZeneca withdrew its EU marketing authorisation application for Iressa following data from the Phase III ISEL (IRESSA Survival Evaluation in Lung cancer) study in pretreated patients not eligible for further CT. ISEL did not meet its primary objective of a statistically significant improvement in OS for Iressa compared to placebo, but did confirm a number of important clinical benefits, including tumour shrinkage and a significant improvement in time-to-treatment failure. The refractory nature of the ISEL population is the most likely explanation for the magnitude of the survival improvement with Iressa, compared to placebo, not reaching statistical significance.
But what sort of a comeback will Iressa be making? Only a day after the CHMP decision, Roche announced that it is collaborating on a trial to investigate Tarceva (erlotinib) in LC patients with genetic mutations in EGFr. The results from the EURTAC trial, if positive, will support a submission by Roche to the EMEA to seek an additional new indication for use of Tarceva, putting it in direct competition with Iressa. Tarceva is already approved, and unlike Iressa, has been shown to benefit all patients, whether or not they have a mutated version of EGFr. Based on this, it looks likely that Iressa will become a niche product. However, a launched product is better for AstraZeneca than one sat on the shelf.
Matthew Dennis - Editor, Cancer Drug News
Thursday, April 30, 2009
Wednesday, April 22, 2009
Provenge finally meets expectations
Dendreon's pivotal Phase III IMPACT (IMmunotherapy for Prostate AdenoCarcinoma Treatment; also known as D9902B) study of Provenge (sipuleucel-T) in men with advanced prostate cancer (PCA) has met its primary endpoint of improving overall survival (OS) compared to placebo. The magnitude of the survival difference observed in the intent-to-treat population resulted in the study successfully achieving the prespecified level of statistical significance defined by its design. The safety profile of Provenge appeared to be consistent with prior studies.
The 512-patient, randomised, placebo-controlled study enrolled men with metastatic androgen-independent PCA and was conducted under a Special Protocol Assessment (SPA) agreement with the FDA. Because the data meet the criteria and specifications outlined in the SPA, Dendreon intends to file an amendment to its existing BLA in the fourth quarter of this year. News of the success triggered a huge jump in the company's share price. After closing on 13th April at US$7.30, the stock rose to a high of US$22.10 on 14th April, a 202 per cent increase.
It is expected that Dendreon will form an international partnership in the third quarter of the year to commercialise the vaccine, although the company will likely market Provenge alone in the US. Some analysts predict that once approved, Provenge could reach peak annual sales of US$2 billion. The vaccine is expected to achieve rapid uptake based on the survival benefit and good safety profile alone.
Detailed results from the trial will be presented during a plenary session at the American Urological Association Annual Meeting, to be held from 25th to 30th April, in Chicago, IL. Provenge may represent the first in a new class of active cellular immunotherapies specifically designed to engage the patient's own immune system against cancer.
Although the success of the trial has been heralded as a breakthrough for therapeutic cancer vaccines, it has also reignited debate about the FDA’s strict guidelines for drug approvals, and especially for innovative medicines. Two years age, the Agency decided not to approve Provenge despite an endorsement by one of its Advisory Committees, which recommended that there was substantial evidence supporting the efficacy and safety of the vaccine. In making its recommendations, the Advisory Committee was asked if the submitted data established that Provenge was reasonably safe and whether there was substantial evidence that the product was efficacious. The Advisory Committee voted 17 to 0 in favour of the safety of Provenge and 13 to 4 in favour of the efficacy question.
However, the FDA went against the Advisory Committee and requested additional clinical data in support of the efficacy claim contained in the submission. Now that the results are available from the IMPACT study, the FDA will be under increasing pressure to approve the vaccine, especially as the conditions in the SPA that the Agency agreed with Dendreon look to have been met. What could now stand in the way of approval? Possibly, quality control regarding the manufacture of the vaccine.
Matthew Dennis - Editor, Cancer Drug News
The 512-patient, randomised, placebo-controlled study enrolled men with metastatic androgen-independent PCA and was conducted under a Special Protocol Assessment (SPA) agreement with the FDA. Because the data meet the criteria and specifications outlined in the SPA, Dendreon intends to file an amendment to its existing BLA in the fourth quarter of this year. News of the success triggered a huge jump in the company's share price. After closing on 13th April at US$7.30, the stock rose to a high of US$22.10 on 14th April, a 202 per cent increase.
It is expected that Dendreon will form an international partnership in the third quarter of the year to commercialise the vaccine, although the company will likely market Provenge alone in the US. Some analysts predict that once approved, Provenge could reach peak annual sales of US$2 billion. The vaccine is expected to achieve rapid uptake based on the survival benefit and good safety profile alone.
Detailed results from the trial will be presented during a plenary session at the American Urological Association Annual Meeting, to be held from 25th to 30th April, in Chicago, IL. Provenge may represent the first in a new class of active cellular immunotherapies specifically designed to engage the patient's own immune system against cancer.
Although the success of the trial has been heralded as a breakthrough for therapeutic cancer vaccines, it has also reignited debate about the FDA’s strict guidelines for drug approvals, and especially for innovative medicines. Two years age, the Agency decided not to approve Provenge despite an endorsement by one of its Advisory Committees, which recommended that there was substantial evidence supporting the efficacy and safety of the vaccine. In making its recommendations, the Advisory Committee was asked if the submitted data established that Provenge was reasonably safe and whether there was substantial evidence that the product was efficacious. The Advisory Committee voted 17 to 0 in favour of the safety of Provenge and 13 to 4 in favour of the efficacy question.
However, the FDA went against the Advisory Committee and requested additional clinical data in support of the efficacy claim contained in the submission. Now that the results are available from the IMPACT study, the FDA will be under increasing pressure to approve the vaccine, especially as the conditions in the SPA that the Agency agreed with Dendreon look to have been met. What could now stand in the way of approval? Possibly, quality control regarding the manufacture of the vaccine.
Matthew Dennis - Editor, Cancer Drug News
Wednesday, April 8, 2009
GSK looks to expand use of lapatinib; to appeal NICE decision
GlaxoSmithKline has simultaneously submitted regulatory applications in the EU and US to expand the use of Tyverb/Tykerb (lapatinib) to include the first-line treatment of breast cancer (BC). The variation to the EU marketing authorisation and the sNDA were submitted, respectively, to the EMEA and to the FDA for the combination of lapatinib plus an aromatase inhibitor for use in patients with hormone-sensitive, metastatic BC.
The submissions are based on results from the recent EGF30008 study, which evaluated lapatinib plus Novartis' aromatase inhibitor, Femara (letrozole), in women with hormone receptor-positive metastatic BC that may or may not overexpress the HER2-positive receptor. Results from the study showed that women experienced a 5.2 month increase in median progression-free survival when treated with lapatinib+letrozole, compared to those treated with letrozole alone. Results from the intent-to-treat group showed that lapatinib+letrozole provided an additional 1.1 month before disease progression, compared to letrozole treatment alone.
Lapatinib, in combination with capecitabine, is currently authorised in 74 countries. In March 2007, the FDA approved lapatinib in combination with capecitabine for the treatment of patients with advanced or metastatic BC whose tumours overexpress HER2/ErbB2 and who have received prior therapy, including an anthracycline, a taxane and Herceptin (trastuzumab). In June 2008, the EC granted a conditional marketing authorisation for lapatinib in all 27 EU member states.
According to Espicom Business Intelligence, sales of lapatinib in BC could reach US$1,732 million by 2014; however, longer-term sales will be partially impacted by the launch of other targeted therapies, such as Roche’s pertuzumab, which is anticipated to be launched in 2012. Even if the drug is approved for first-line treatment, it may still not reach patients in some countries. GSK has recently stated that it is to appeal the UK's National Institute for Health and Clinical Excellence (NICE) decision in March to recommend against funding lapatinib, in combination with capecitabine, for women with advanced BC. If successful, the appeal will enable the NHS to offer a similar level of access to lapatinib as other EU countries where it has been granted funding, which incclude Slovenia, Slovakia, France, Spain, Germany, Italy and Ireland.
Although NICE acknowledged that lapatinib is an effective treatment for eligible women, it was rejected on the grounds that it was not a cost-effective use of NHS resources. This decision was reached despite GSK offering a patient access programme whereby the cost of up to 12 weeks' treatment would be paid by the company. GSK's analysis suggests that the cost-effectiveness of lapatinib in the context of the patient access programme (sensitive to the proportion of trastuzumab used in clinical practice) demonstrated a cost per QALY gain for lapatinib of just over £16,000 versus the usual care given to these patients, which includes standard chemotherapy and trastuzumab regimens.
Matthew Dennis - Editor, Cancer Drug News
The submissions are based on results from the recent EGF30008 study, which evaluated lapatinib plus Novartis' aromatase inhibitor, Femara (letrozole), in women with hormone receptor-positive metastatic BC that may or may not overexpress the HER2-positive receptor. Results from the study showed that women experienced a 5.2 month increase in median progression-free survival when treated with lapatinib+letrozole, compared to those treated with letrozole alone. Results from the intent-to-treat group showed that lapatinib+letrozole provided an additional 1.1 month before disease progression, compared to letrozole treatment alone.
Lapatinib, in combination with capecitabine, is currently authorised in 74 countries. In March 2007, the FDA approved lapatinib in combination with capecitabine for the treatment of patients with advanced or metastatic BC whose tumours overexpress HER2/ErbB2 and who have received prior therapy, including an anthracycline, a taxane and Herceptin (trastuzumab). In June 2008, the EC granted a conditional marketing authorisation for lapatinib in all 27 EU member states.
According to Espicom Business Intelligence, sales of lapatinib in BC could reach US$1,732 million by 2014; however, longer-term sales will be partially impacted by the launch of other targeted therapies, such as Roche’s pertuzumab, which is anticipated to be launched in 2012. Even if the drug is approved for first-line treatment, it may still not reach patients in some countries. GSK has recently stated that it is to appeal the UK's National Institute for Health and Clinical Excellence (NICE) decision in March to recommend against funding lapatinib, in combination with capecitabine, for women with advanced BC. If successful, the appeal will enable the NHS to offer a similar level of access to lapatinib as other EU countries where it has been granted funding, which incclude Slovenia, Slovakia, France, Spain, Germany, Italy and Ireland.
Although NICE acknowledged that lapatinib is an effective treatment for eligible women, it was rejected on the grounds that it was not a cost-effective use of NHS resources. This decision was reached despite GSK offering a patient access programme whereby the cost of up to 12 weeks' treatment would be paid by the company. GSK's analysis suggests that the cost-effectiveness of lapatinib in the context of the patient access programme (sensitive to the proportion of trastuzumab used in clinical practice) demonstrated a cost per QALY gain for lapatinib of just over £16,000 versus the usual care given to these patients, which includes standard chemotherapy and trastuzumab regimens.
Matthew Dennis - Editor, Cancer Drug News
Wednesday, March 25, 2009
Caution raised over integrin inhibitors
When designing drugs to target and treat cancer, the last thing that you want to happen is for the agents to actually promote tumour growth. But this is what a study by scientists from the UK has found is the case when low doses of an experimental angiogenesis inhibitor were given to mouse models. However, there is hope that turning the findings on their head will help in the development of new ways to make these drugs as effective as possible. In the future, it may be feasible to combine these inhibitors with other drugs to maximise their effectiveness for patients.
Angiogenesis inhibitors are designed to block the supply of blood to the tumour to prevent it from growing. Some of these have proven successful in the clinic and gone on to be widely used, such as Avastin (bevacizumab) and Sutent (sunitinib), while others, such as those that inhibit the v3 and v5 integrins, have entered clinical trials but have generally been unsuccessful.
One such agent under development that targets integrins is cilengitide, which is thought to work by targeting the tumour and its vasculature. The agent is currently being investigated in a Phase III trial for the treatment of glioblastoma multiforme (GBM), as well as a number of Phase II studies in several indications, including advanced non-small cell lung cancer and squamous cell carcinoma of the head and neck. Now, scientists from the Institute of Cancer, Queen Mary's University London, the Institute of Cancer Research and the Beatson Institute for Cancer Research have found evidence to suggest that low doses of cilengitide in laboratory studies can have the opposite effect to what was expected and promote cancer growth.
The work, which was published in the 22nd March online edition of Nature Medicine (10.1038/nm.1941), showed that low concentrations of the drug promoted VEGF-mediated angiogenesis by altering v3 integrin and VEGFr-2 trafficking, thereby promoting endothelial cell migration to VEGF. The study found that while higher concentrations of cilengitide can block angiogenesis, lower concentrations can actually stimulate the supply of blood to the tumour and can promote its growth. These results may explain why initial results from early-stage clinical trials have not been as promising as hoped.
Cilengitide is being developed by Merck Serono (Merck KGaA), which in response to the Nature Medicine article issued a statement citing previous findings in numerous preclinical models of the drug in vitro and in vivo that diverge from the latest results. The company also countered with the fact that cilengitide has been studied in more than 750 patients in various long-term settings supporting its current development. Notably, the clinical data for cilengitide in the treatment of GBM, both as a single agent and in combination, have been encouraging. However, all current Merck Serono studies are investigating cilengitide in combination treatment (either radiotherapy and chemotherapy or chemotherapy and another targeted therapy), so there may be some truth in the fact that this class of drugs will not have utility as single agents. Only time will tell.
Matthew Dennis - Editor, Cancer Drug News
Angiogenesis inhibitors are designed to block the supply of blood to the tumour to prevent it from growing. Some of these have proven successful in the clinic and gone on to be widely used, such as Avastin (bevacizumab) and Sutent (sunitinib), while others, such as those that inhibit the v3 and v5 integrins, have entered clinical trials but have generally been unsuccessful.
One such agent under development that targets integrins is cilengitide, which is thought to work by targeting the tumour and its vasculature. The agent is currently being investigated in a Phase III trial for the treatment of glioblastoma multiforme (GBM), as well as a number of Phase II studies in several indications, including advanced non-small cell lung cancer and squamous cell carcinoma of the head and neck. Now, scientists from the Institute of Cancer, Queen Mary's University London, the Institute of Cancer Research and the Beatson Institute for Cancer Research have found evidence to suggest that low doses of cilengitide in laboratory studies can have the opposite effect to what was expected and promote cancer growth.
The work, which was published in the 22nd March online edition of Nature Medicine (10.1038/nm.1941), showed that low concentrations of the drug promoted VEGF-mediated angiogenesis by altering v3 integrin and VEGFr-2 trafficking, thereby promoting endothelial cell migration to VEGF. The study found that while higher concentrations of cilengitide can block angiogenesis, lower concentrations can actually stimulate the supply of blood to the tumour and can promote its growth. These results may explain why initial results from early-stage clinical trials have not been as promising as hoped.
Cilengitide is being developed by Merck Serono (Merck KGaA), which in response to the Nature Medicine article issued a statement citing previous findings in numerous preclinical models of the drug in vitro and in vivo that diverge from the latest results. The company also countered with the fact that cilengitide has been studied in more than 750 patients in various long-term settings supporting its current development. Notably, the clinical data for cilengitide in the treatment of GBM, both as a single agent and in combination, have been encouraging. However, all current Merck Serono studies are investigating cilengitide in combination treatment (either radiotherapy and chemotherapy or chemotherapy and another targeted therapy), so there may be some truth in the fact that this class of drugs will not have utility as single agents. Only time will tell.
Matthew Dennis - Editor, Cancer Drug News
Wednesday, March 18, 2009
Dendreon surges on Provenge hope
Shares in Dendreon have increased dramatically over the past few days, possibly as the result of investors trying to cash in before the company releases final results from its make-or-break IMPACT (IMmunotherapy for Prostate AdenoCarcinoma Treatment; also known as D9902B) study. The trial is designed to assess the safety and efficacy of the investigational active cellular immunotherapy, Provenge (sipuleucel-T), in men with metastatic androgen-independent prostate cancer (PCA). Dendreon’s shares closed at US$4.05 on 13th March, up 46 per cent on the closing price on 11th March of US$2.77.
The latest price increase was likely triggered by the release of Dendreon’s fourth quarter and 2008 year-end financial results on 12th March, confirming that it anticipates the IMPACT study to continue to its final analysis, which is expected to be completed by the end of April. Favourable blinded, interim results from the trial were previously reported in October 2008, when the independent Data Monitoring Committee (IDMC), which is overseeing the trial, recorded a 20 per cent reduction in the risk of death in the Provenge arm relative to placebo (hazard ratio=0.80; 95% CI, 0.610 to 1.051). The IDMC observed no safety concerns and recommended that the study continues as planned. However, at that time the company only announced that the final analysis was anticipated in the middle of 2009.
At the final analysis, if the study demonstrates approximately a 22 per cent reduction in the risk of death, based on 304 events, the company would expect the trial to meet its primary endpoint of overall survival (OS). Should the prespecified criterion for statistical significance be achieved, Dendreon would anticipate amending its BLA based on these interim results. The initial BLA filing was based primarily on an improvement in OS observed in the Phase III D9901 trial. Following an FDA Advisory Committee vote that there was substantial evidence of efficacy of Provenge and that it was reasonably safe, the Agency requested additional clinical data to support the proposed efficacy claim. The FDA has since indicated that either a positive interim or final analysis for OS from the IMPACT trial would be sufficient to address the request for additional information to support the proposed efficacy claim.
Sipuleucel-T contains mature, autologous antigen presenting cells (APCs) that are obtained from the patient via a standard procedure approximately two days before each scheduled infusion. The patient's APCs are then transported to a Dendreon manufacturing facility where they are co-cultured with a recombinant fusion protein containing prostatic acid phosphatase. The activated, antigen-loaded APCs (now sipuleucel-T) are then delivered to the physician's office for infusion into the patient. Sipuleucel-T is then infused into the patient, where it can potentially stimulate a T-cell response against PCA cells. Well, that is the theory anyway, and investors buying up Dendreon’s shares will hope that is also the case in the IMPACT study. They will also have their fingers crossed that the company can hit the heady heights of April 2007, when its shares reached US$23.58.
Matthew Dennis - Editor, Cancer Drug News
The latest price increase was likely triggered by the release of Dendreon’s fourth quarter and 2008 year-end financial results on 12th March, confirming that it anticipates the IMPACT study to continue to its final analysis, which is expected to be completed by the end of April. Favourable blinded, interim results from the trial were previously reported in October 2008, when the independent Data Monitoring Committee (IDMC), which is overseeing the trial, recorded a 20 per cent reduction in the risk of death in the Provenge arm relative to placebo (hazard ratio=0.80; 95% CI, 0.610 to 1.051). The IDMC observed no safety concerns and recommended that the study continues as planned. However, at that time the company only announced that the final analysis was anticipated in the middle of 2009.
At the final analysis, if the study demonstrates approximately a 22 per cent reduction in the risk of death, based on 304 events, the company would expect the trial to meet its primary endpoint of overall survival (OS). Should the prespecified criterion for statistical significance be achieved, Dendreon would anticipate amending its BLA based on these interim results. The initial BLA filing was based primarily on an improvement in OS observed in the Phase III D9901 trial. Following an FDA Advisory Committee vote that there was substantial evidence of efficacy of Provenge and that it was reasonably safe, the Agency requested additional clinical data to support the proposed efficacy claim. The FDA has since indicated that either a positive interim or final analysis for OS from the IMPACT trial would be sufficient to address the request for additional information to support the proposed efficacy claim.
Sipuleucel-T contains mature, autologous antigen presenting cells (APCs) that are obtained from the patient via a standard procedure approximately two days before each scheduled infusion. The patient's APCs are then transported to a Dendreon manufacturing facility where they are co-cultured with a recombinant fusion protein containing prostatic acid phosphatase. The activated, antigen-loaded APCs (now sipuleucel-T) are then delivered to the physician's office for infusion into the patient. Sipuleucel-T is then infused into the patient, where it can potentially stimulate a T-cell response against PCA cells. Well, that is the theory anyway, and investors buying up Dendreon’s shares will hope that is also the case in the IMPACT study. They will also have their fingers crossed that the company can hit the heady heights of April 2007, when its shares reached US$23.58.
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
Synta suspends SYMMETRY study
Based on an analysis by an independent Data Monitoring Committee (DMC), Synta Pharmaceuticals has suspended the Phase III SYMMETRY (Synta Metastatic Melanoma Elesclomol Trial) trial, which was comparing elesclomol (STA-4783) in combination with paclitaxel to paclitaxel alone in chemotherapy-naïve patients with Stage IV metastatic melanoma. Following the suspension, shares in Synta fell from US$6.39 at the end of 26th February to close on 27th February at US$1.36, a decrease in value of nearly 79 per cent.
The decision was based on the results of an analysis by the DMC, which identified safety concerns, including an imbalance in overall survival, with a greater number of deaths occurring in the combination arm (elesclomol+paclitaxel) compared to the control arm of paclitaxel alone. The final analysis of the primary endpoint (progression-free survival) as assessed by independent reviewers has not been carried out yet. Elesclomol is an apoptosis stimulator, which acts by inducing oxidative stress in cancer cells by rapidly producing reactive oxygen species. Response to this oxidative stress leads to apoptosis.
Based on these findings, Synta has also revealed that additional ongoing studies with elesclomol, including a study of elesclomol in combination with docetaxel in hormone-refractory metastatic prostate cancer and a monotherapy dose-escalation study, will be suspended pending further analysis of the results of the SYMMETRY trial. Synta is contacting investigators regarding appropriate patient notification and care. The company is also in discussions with its collaborator, GlaxoSmithKline, about the future development of elesclomol. However, it looks likely that GSK will terminate the collaboration.
Such a huge setback could spell the end for Synta, especially in the current economic climate. However, the company has stated that it has both the resources and a diverse pipeline of novel drug candidates in the oncology and anti-inflammatory areas that will allow it to continue operating. The company has recently received two milestone payments that should help its current cash position. These include an up-front payment of US$16 million from Roche for the development of the Synta CRACM (calcium release-activated calcium modulator) programme for the treatment of inflammatory and autoimmune diseases, as well as committed research funding of US$9 million over the next two years. The second payment of US$10 million was received from GSK after Synta achieved a milestone related to the development of elesclomol.
Synta's pipeline includes: STA-9090, a novel heat shock protein 90 inhibitor that is currently in two Phase I studies in solid tumours; STA-5326 (apilimod mesylate), an oral interleukin (IL)-12/IL-23 inhibitor currently in a Phase IIa study in rheumatoid arthritis; STA-9584, a vascular disrupting agent for cancer in preclinical development; and additional programmes in the research and preclinical development stages. Synta shareholders will hope that these programmes prove more successful than elesclomol.
Matthew Dennis - Editor, Cancer Drug News
The decision was based on the results of an analysis by the DMC, which identified safety concerns, including an imbalance in overall survival, with a greater number of deaths occurring in the combination arm (elesclomol+paclitaxel) compared to the control arm of paclitaxel alone. The final analysis of the primary endpoint (progression-free survival) as assessed by independent reviewers has not been carried out yet. Elesclomol is an apoptosis stimulator, which acts by inducing oxidative stress in cancer cells by rapidly producing reactive oxygen species. Response to this oxidative stress leads to apoptosis.
Based on these findings, Synta has also revealed that additional ongoing studies with elesclomol, including a study of elesclomol in combination with docetaxel in hormone-refractory metastatic prostate cancer and a monotherapy dose-escalation study, will be suspended pending further analysis of the results of the SYMMETRY trial. Synta is contacting investigators regarding appropriate patient notification and care. The company is also in discussions with its collaborator, GlaxoSmithKline, about the future development of elesclomol. However, it looks likely that GSK will terminate the collaboration.
Such a huge setback could spell the end for Synta, especially in the current economic climate. However, the company has stated that it has both the resources and a diverse pipeline of novel drug candidates in the oncology and anti-inflammatory areas that will allow it to continue operating. The company has recently received two milestone payments that should help its current cash position. These include an up-front payment of US$16 million from Roche for the development of the Synta CRACM (calcium release-activated calcium modulator) programme for the treatment of inflammatory and autoimmune diseases, as well as committed research funding of US$9 million over the next two years. The second payment of US$10 million was received from GSK after Synta achieved a milestone related to the development of elesclomol.
Synta's pipeline includes: STA-9090, a novel heat shock protein 90 inhibitor that is currently in two Phase I studies in solid tumours; STA-5326 (apilimod mesylate), an oral interleukin (IL)-12/IL-23 inhibitor currently in a Phase IIa study in rheumatoid arthritis; STA-9584, a vascular disrupting agent for cancer in preclinical development; and additional programmes in the research and preclinical development stages. Synta shareholders will hope that these programmes prove more successful than elesclomol.
Matthew Dennis - Editor, Cancer Drug News
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