Global Insight Perspective | |
Significance | AstraZeneca has given an update on the clinical progress of its oncology drug Zactima (vandetanib) in lung cancer with the release of three independent late-stage studies. In the meantime, the company was dealt a blow as the U.S. FDA has approved a generic version of its asthma drug Pulmicort Respules (budesonide inhalation suspension). |
Implications | The Zactima clinical studies bring AstraZeneca closer to a potential regulatory filing for its drug potentially in the first half of 2009. On the Pulmicort Respules front, the FDA decision puts Israeli generic manufacturer Teva in a position to initiate an "at risk" launch of the asthma drug. |
Outlook | AstraZeneca may soon be in a position to have a share of the lucrative NSCLC market although Zactima could face an uphill battle to position itself in the segment. Regarding Pulmicort Respules, the company will have to carefully weigh its options as if it fails to enforce its IP rights over the drug it will cut market exclusivity by 10 years. Although AstraZeneca is convinced its patent will be upheld, a deal with Teva might also be considered. |
Anglo-Swedish drug giant AstraZeneca has unveiled the results of three independent Phase III clinical studies evaluating the benefits of oncology drug Zactima (vandetanib) in non-small cell lung cancer (NSCLC) while the U.S. FDA dealt the company a blow by approving a generic version of its asthma drug Pulmicort Respules (budesonide inhalation suspension).
In the randomised, double-blind and placebo-controlled Zodiac study, which enrolled 1,391 patients who had previously received one treatment for their advanced NSCLC, combination therapy between Zactima 100 mg and docetaxel (Taxotere; Sanofi Aventis, France) was compared to Taxotere monotherapy. In the randomised, double-blind and placebo-controlled Zeal study, which enrolled 534 patients who had previously received one treatment for their advanced NSCLC, combination therapy between Zactima 100 mg and pemetrexed (Alimta; Eli Lilly, U.S.) was compared to Alimta monotherapy. The primary endpoint of the studies was progression free survival (PFS) while the secondary endpoints were objective response rate (ORR), an indicator of tumour shrinkage, and overall survival (OS). Zactima combination therapy demonstrated PFS benefits in the Zodiac study but failed to do so in the Zeal study. In addition, Zactima combination therapy demonstrated ORR benefits in both the Zodiac and Zeal studies. Finally, Zactima combination therapy did not statistically demonstrate OS benefits, although AstraZeneca noted a positive trend towards the endpoint, in both the Zodiac and Zeal studies. Specific details of the results were not provided.
In the randomised, double-blind and placebo-controlled Zest study, which enrolled 1,240 patients who had previously received at least one treatment for their advanced or metastatic NSCLC, Zactima 300-mg monotherapy was compared to erlotinib 150-mg (Tarceva; Roche/Genentech, Switzerland/U.S.) monotherapy. In this study, Zactima failed to demonstrate superiority to Tarceva in terms of statistically-prolonged PFS, the primary endpoint of the study. Zactima was nevertheless found non-inferior to Tarceva in terms of PFS and OS.
Zactima is a dual vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibitor. As it also is a RET-tyrosine kinase inhibitor, Zactima is currently undergoing clinical development in the treatment of thyroid cancer. The drug has faced some delays in clinical trials and is not expected to be filed for regulatory approval before the first half of 2009 at the earliest.
In the meantime, AstraZeneca has announced that the FDA has granted Israeli generic company Teva, a marketing authorisation for a generic version of Pulmicort Respules. The two companies are embattled in a patent-infringement lawsuit over the drug, which is due to be heard in court starting 12 January 2009 (see United States - United Kingdom - Israel: 24 September 2008: AstraZeneca Wins First Battle in Asthma Drug Pulmicort U.S. Patent Litigation). Pulmicort Respules's U.S. patent runs until 2019, inclusive of paediatric exclusivity extension. The drug is licensed in the preventive and maintenance treatment of asthmatic children aged 12 months to 8 years old. The Pulmicort franchise garnered 2007 global sales of US$964 million, 90% of which could be attributed to Pulmicort Respules.
Outlook and Implications
The clinical results for Zactima bring AstraZeneca one step closer to regulatory filing in a second-line NSCLC indication. Although the NSCLC segment is becoming crowded, it remains an area of high unmet clinical need. The market is also sizeable as lung cancer is the most common form of cancer and NSCLC accounts for about 85% of all lung cancers. The lack of specific data makes it hard to assess how Zactima really fares compared to competition but the drug differentiates itself by being a dual VEGF and EGFR inhibitor. The drug's failure to demonstrate superiority to Tarceva as a second-line monotherapy could be an area of concern as it could make it hard for Zactima to eat into Tarceva's market share unless its price is attractive. In addition, both Lilly and Genentech are currently developing Alimta and Tarceva as first-line therapies, which if successful, might also limit Zactima's commercial potential. Nevertheless, AstraZeneca will find comfort in the present results after the failure of its once-highly touted EGFR/TK inhibitor Iressa (geftinib) in this setting in late 2004.
On the Pulmicort Respules front, the FDA approval is a blow for AstraZeneca as Teva is now in a position to launch its generic version of the drug. Indeed, the generic drug maker could choose not to wait for the court hearing regarding the patent litigation. An "at risk" launch has some downsides for the generic company as if Pulmicort Respules's U.S. patent is upheld in court, Teva will have to pay triple damages. Teva will have to weigh its options as there could be other roads to explore. Indeed, the two companies may consider a deal where AstraZeneca retains continued marketing exclusivity of the product for a certain period in return for a financial settlement with Teva. In addition, AstraZeneca and Teva might want to explore a deal similar to that stroke between German company Bayer Schering and U.S. generic company Barr over oral contraceptives Yasmin and Yaz (both drospirenone and ethinyl estradiol, see United States – Germany: 28 June 2008: Bayer, Barr Strike Deal On Generic Oral Contraceptives Yasmin, Yaz). The stakes are high for AstraZeneca as the drug's patent runs for another 10 years. The company might have to look into a damage limitation strategy if it is not certain to be able to enforce its intellectual property rights.