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
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