AstraZeneca updates on olaparib and TC-5214 development programmes

AstraZeneca has announced that its investigational compound olaparib will not progress into Phase III development for the maintenance treatment of serous ovarian cancer. In addition, AstraZeneca announced that the second RENAISSANCE Phase III study of TC-5214 for patients with major depressive disorder did not meet its primary end point. As a result, AstraZeneca will take pre-tax impairment charges totalling $381.5 million to R&D expense in the fourth quarter of 2011. The company confirms its expectation for full year Core EPS in the range of $7.20 to $7.40, but with the inclusion of these intangible impairments, Core EPS is likely to be in the lower half of this range.

The decision to discontinue olaparib’s development in serous ovarian cancer was made following a review of an interim analysis of a Phase II study (study 19) which indicated that the previously reported progression free survival benefit is unlikely to translate into an overall survival benefit, the definitive measure of patient benefit in ovarian cancer. In addition, attempts to identify a suitable tablet dose for use in Phase III studies have not been successful. No new safety concerns were identified for patients.

With respect to TC-5214, the second of four Phase III efficacy and tolerability studies of the compound as an adjunct therapy to an antidepressant in patients with major depressive disorder who do not respond adequately to initial antidepressant treatment, did not meet its primary end point. The target measure was change in the Montgomery-Asberg Depression Rating Scale total score after eight weeks of treatment with TC-5214 as compared to placebo. TC-5214 was overall well tolerated in RENAISSANCE 2 and showed an adverse event profile generally consistent with prior clinical trials of TC-5214. Analyses of the full data set from the RENAISSANCE 2 are ongoing.

These results follow the recent announcement of top-line results of the RENAISSANCE flexible dose trial study 3, which also did not meet its primary endpoint. AstraZeneca will continue with the development of the two remaining fixed dose Phase III RENAISSANCE efficacy and tolerability studies and one long-term safety study. Regulatory filing targets will be reviewed following full results of the remaining studies which are expected in the first half of 2012. A potential New Drug Application filing in the US is planned for the second half of 2012, with an EU Marketing Authorisation Application targeted for 2015.

As a result of the termination of further development of olaparib in serous ovarian cancer, the company is taking an impairment of $285 million pre-tax charge. A further impairment of $96.5 million pre-tax charge will also be taken based on the lower probability of success for the remaining TC-5214 studies. The value of the remaining intangible assets held in relation to TC-5214 amount to $96.5 million.

These impairments will have an approximately $0.21 negative impact on the company’s Core EPS in the fourth quarter. The company’s Core EPS guidance remains unchanged at between $7.20 and $7.40 per share, although it is now likely that Core EPS will be in the lower half of this range.