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
Thursday, June 4, 2009
Thursday, May 28, 2009
Looking ahead to ASCO
As the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO) looms, there is just time to look at the data and presentations that will be making the biggest impact. The 4,000 study abstracts for this years Meeting, to be held from 29th May to 2nd June, in Orlando, FL, have now been published, and have drawn a mainly disappointing response. However, there are some biotech companies that will be worth keeping an eye on.
One such company with positive results to present is OncoGenex Pharmaceuticals, whose investigational prostate cancer (PCA) drug, OGX-011, has produced promising Phase II results. Some analysts have commented that the data could be significantly better than Dendreon’s Provenge (sipuleucel-T). At the time results were submitted to ASCO, the preliminary median overall survival in patients with advanced PCA who were treated with OGX-011 plus docetaxel was 27.5 months compared to 16.9 months for patients treated with docetaxel alone. Final survival data as of April for this trial will be presented during the Meeting.
Another company to report encouraging results will be Exelixis, from a Phase II study of XL184 in patients with progressive glioblastoma multiforme. The drug is being co-developed with Bristol-Myers Squibb. In the trial, XL184 was shown to shrink brain tumours in some patients, according to interim results. At four weeks, 26 patients have been assessed. Ten of them (38 per cent) had tumour shrinkage of at least 50 per cent, including one patient who had a 100 per cent reduction in tumour size. Nine patients had tumour measurement changes ranging from 24 to -49 per cent and seven had at least a 25 per cent increase in tumour burden. Of 17 patients who had not received prior anti-angiogenic treatment, nine had at least a 50 per cent reduction in tumour burden.
OSI Pharmaceuticals will also create a lot of attention at the Meeting. The company will present data from two Phase III studies looking at the use of its drug Tarceva (erlotinib) as front-line maintenance therapy in patients with non-small cell lung cancer. OSI hopes that the data from the two studies, called SATURN and ATLAS (AVF3671g), will convince physicians to use the drug, which is co-marketed with Roche, more in the maintenance setting. However, results showed only a small gain over placebo in the time before disease progressed for certain lung cancer patients, leaving many onlookers less than impressed with the data.
Apart from these presentations, there seems little to get excited about. Roche will present data on the use of adjuvant Avastin (bevacizumab) in colon cancer, but the company has already disclosed the study's failure to produce a significant survival benefit. Results of that trial, known as C08, along with around 30 late-breaking studies will be unveiled at the Meeting, which will hopefully hold more surprises than the published abstracts.
Matthew Dennis - Editor, Cancer Drug News
One such company with positive results to present is OncoGenex Pharmaceuticals, whose investigational prostate cancer (PCA) drug, OGX-011, has produced promising Phase II results. Some analysts have commented that the data could be significantly better than Dendreon’s Provenge (sipuleucel-T). At the time results were submitted to ASCO, the preliminary median overall survival in patients with advanced PCA who were treated with OGX-011 plus docetaxel was 27.5 months compared to 16.9 months for patients treated with docetaxel alone. Final survival data as of April for this trial will be presented during the Meeting.
Another company to report encouraging results will be Exelixis, from a Phase II study of XL184 in patients with progressive glioblastoma multiforme. The drug is being co-developed with Bristol-Myers Squibb. In the trial, XL184 was shown to shrink brain tumours in some patients, according to interim results. At four weeks, 26 patients have been assessed. Ten of them (38 per cent) had tumour shrinkage of at least 50 per cent, including one patient who had a 100 per cent reduction in tumour size. Nine patients had tumour measurement changes ranging from 24 to -49 per cent and seven had at least a 25 per cent increase in tumour burden. Of 17 patients who had not received prior anti-angiogenic treatment, nine had at least a 50 per cent reduction in tumour burden.
OSI Pharmaceuticals will also create a lot of attention at the Meeting. The company will present data from two Phase III studies looking at the use of its drug Tarceva (erlotinib) as front-line maintenance therapy in patients with non-small cell lung cancer. OSI hopes that the data from the two studies, called SATURN and ATLAS (AVF3671g), will convince physicians to use the drug, which is co-marketed with Roche, more in the maintenance setting. However, results showed only a small gain over placebo in the time before disease progressed for certain lung cancer patients, leaving many onlookers less than impressed with the data.
Apart from these presentations, there seems little to get excited about. Roche will present data on the use of adjuvant Avastin (bevacizumab) in colon cancer, but the company has already disclosed the study's failure to produce a significant survival benefit. Results of that trial, known as C08, along with around 30 late-breaking studies will be unveiled at the Meeting, which will hopefully hold more surprises than the published abstracts.
Matthew Dennis - Editor, Cancer Drug News
Thursday, May 21, 2009
RCC: targeted therapies increase survival
The arrival of targeted therapies has dramatically improved outcomes for patients with renal cell carcinoma (RCC). With approvals of Bayer/Onyx Pharmaceuticals' Nexavar (sorafenib), Pfizer's Sutent (sunitinib), Novartis' Afinitor (everolimus) and Wyeth's Torisel (temsirolimus), doctors now have a anumber of agents to choose from to treat patients.
However, due to the fact that in subjects with advanced RCC, who are receiving therapy, their disease will ultimately progress, physicians must choose from the drugs available to best extend survival whilst preserving quality of life. This requires consideration of the overall treatment plan from the outset, so that when selecting which agent to start treatment with, the doctor must contemplate effective options for subsequent therapy.
Current retrospective data suggest that there is no cross-resistance between tyrosine kinase inhibitors (TKIs), which means that they can be effectively used in sequence. These data also hint to a preferred treatment sequence, where patients treated with sorafenib prior to sunitinib may experience longer periods of progression-free survival compared with those receiving sunitinib then sorafenib. Furthermore, Phase III evidence indicates that the mTOR inhibitor, everolimus, retains full efficacy in patients who have already been treated with both sorafenib and sunitinib. Therefore an optimal sequence, based on currently available evidence, might be two TKIs followed by an mTOR inhibitor.
Further to this, results from a Phase III study have shown that treatment with sunitinib achieved a median overall survival (OS) greater than two years in patients with metastatic RCC. The data support the recent publication of final guidance from the UK's National Institute for Health and Clinical Excellence (NICE), which recommends the use of sunitinib for the first-line treatment of advanced RCC.
The results, published in the online edition of the Journal of Clinical Oncology, also support a recent recommendation made by a group of oncologists in the UK to use sunitinib as a first-line treatment for metastatic RCC.
The trial data showed that the median OS for patients who received sunitinib versus interferon (IFN) alpha was 26.4 versus 21.8 months, respectively (p=0.051). However, an exploratory analysis of patients who received only one line of treatment (ie, no subsequent treatments after stopping their sunitinib or IFN alpha therapies) showed that sunitinib almost doubled the median OS compared to IFN alpha (28.1 vs 14.1 months; hazard ratio=0.647; p=0.003). This is a reflection of clinical practice in the UK where generally patients are only funded for one line of treatment at most.
According to Pfizer, before NICE guidance only one-third of primary care trusts (PCTs) were funding sunitinib to some extent. Since the guidelines were published, 90 per cent of PCTs have committed to full funding of sunitinib in accordance with NICE guidance. In 2007, Pfizer cut the price of sunitinib by 5 per cent and committed to providing one cycle/course of the treatment free of charge to every eligible patient in the UK, in an effort to increase patient access. This move amounts to an average saving of between 19 and 29 per cent per patient for the cost of treatment, depending upon the type and stage of their tumour. The average annual cost for a patient taking sunitinib is £24,168.
Matthew Dennis - Editor, Cancer Drug News
However, due to the fact that in subjects with advanced RCC, who are receiving therapy, their disease will ultimately progress, physicians must choose from the drugs available to best extend survival whilst preserving quality of life. This requires consideration of the overall treatment plan from the outset, so that when selecting which agent to start treatment with, the doctor must contemplate effective options for subsequent therapy.
Current retrospective data suggest that there is no cross-resistance between tyrosine kinase inhibitors (TKIs), which means that they can be effectively used in sequence. These data also hint to a preferred treatment sequence, where patients treated with sorafenib prior to sunitinib may experience longer periods of progression-free survival compared with those receiving sunitinib then sorafenib. Furthermore, Phase III evidence indicates that the mTOR inhibitor, everolimus, retains full efficacy in patients who have already been treated with both sorafenib and sunitinib. Therefore an optimal sequence, based on currently available evidence, might be two TKIs followed by an mTOR inhibitor.
Further to this, results from a Phase III study have shown that treatment with sunitinib achieved a median overall survival (OS) greater than two years in patients with metastatic RCC. The data support the recent publication of final guidance from the UK's National Institute for Health and Clinical Excellence (NICE), which recommends the use of sunitinib for the first-line treatment of advanced RCC.
The results, published in the online edition of the Journal of Clinical Oncology, also support a recent recommendation made by a group of oncologists in the UK to use sunitinib as a first-line treatment for metastatic RCC.
The trial data showed that the median OS for patients who received sunitinib versus interferon (IFN) alpha was 26.4 versus 21.8 months, respectively (p=0.051). However, an exploratory analysis of patients who received only one line of treatment (ie, no subsequent treatments after stopping their sunitinib or IFN alpha therapies) showed that sunitinib almost doubled the median OS compared to IFN alpha (28.1 vs 14.1 months; hazard ratio=0.647; p=0.003). This is a reflection of clinical practice in the UK where generally patients are only funded for one line of treatment at most.
According to Pfizer, before NICE guidance only one-third of primary care trusts (PCTs) were funding sunitinib to some extent. Since the guidelines were published, 90 per cent of PCTs have committed to full funding of sunitinib in accordance with NICE guidance. In 2007, Pfizer cut the price of sunitinib by 5 per cent and committed to providing one cycle/course of the treatment free of charge to every eligible patient in the UK, in an effort to increase patient access. This move amounts to an average saving of between 19 and 29 per cent per patient for the cost of treatment, depending upon the type and stage of their tumour. The average annual cost for a patient taking sunitinib is £24,168.
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
Thursday, April 30, 2009
Iressa set to make it at second asking
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
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
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
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