The latest set of opinions from the European Medicines Agency has brought good news for AstraZeneca and Merck KGaA, while the safety of Boehringer Ingelheim's Pradaxa has been backed despite an increasing number of fatal cases of bleeding in patients treated with the anticoagulant.
First up, the agency's Committee for Medicinal Products for Human Use (CHMP) has recommended AstraZeneca's Caprelsa (vandetanib) for the treatment of medullary thyroid cancer. The drug was once touted as a blockbuster for advanced non-small cell lung cancer but the Anglo-Swedsih drugmaker withdrew marketing applications in October 2009 for the oral kinase inhibitor, then known as Zactima, as it demonstrated no overall survival advantage.
The proposed indication also states that for patients in whom 'rearranged during transfection' mutation is not known or is negative, a possible lower benefit should be taken into account. In line with the CHMP’s requirement, AstraZeneca will conduct a further study to generate additional data to confirm the benefits in patients who are RET negative. Caprelsa was approved by the US Food and Drug Administration in April and analysts have predicted peak sales of around $120 million.
The agency has also recommended expanding the labels on Merck's multiple sclerosis blockbuster Rebif (interferon beta-1a) to cover patients who have experienced a single demyelinating event, an early sign of the disease. The CHMP has also backed extending the indication for the German firm's colorectal cancer drug Erbitux (cetuximab), while expansions for the labels on Roche's Herceptin (trastuzumab) and Novartis unit Alcon's eye drug Nevanac (nepafenac).
In terms of generics, the EMA has granted positive opinions to copies of Merck & Co's antihistamine Clarinex (desloratadine) from Actavis and Teva's Ratiopharm and Mylan's version of Sanofi's cancer drug Taxotere (docetaxel).
The most eye-catching news to come out of the meeting was the EMA's update on the safety of Pradaxa (dabigatran).
As of November 6, 256 cases of serious bleeding resulting in death were recorded in association with the use of Pradaxa, 21 of which were reported in the European Union. The rise is linked to Pradaxa's recent approval of a new indication (prevention of stroke and systemic embolism in adults with non-valvular atrial fibrillation) "and also the increased awareness about the drug", the EMA said.
Last month, the CHMP recommended further changes to the product information following reports of fatal cases of bleeding coming from Japan, which includes advice that renal function be assessed in all patients before starting Pradaxa treatment. The CHMP says the recommended changes "adequately manage the risk of bleeding".
In response, Boehringer noted that it is is aware of 260 cases of fatal bleeding reported globally since the initial registration of Pradaxa in 2008. The firm noted that over 410,000 patient years (the total treatment exposure of patients to the drug), this equates to 63 cases per 100,000 patient years.
In the RE-LY study of over 18,000 patients, the Phase III trial for stroke prevention in atrial fibrillation, rates of fatal bleeding were 0.19% (23 cases) for Pradaxa 110mg, 0.23% (28 cases) for Pradaxa 150mg, and 0.33% (39 cases) for warfarin. Boehringer says that extrapolating these results to 100,000 patients years treatment exposure gives rates of 190, 230 and 330 cases of fatal bleeding respectively.
The company added that "a direct comparison between real life clinical practice and a clinical trial has its limitations but nevertheless this does provide reassurance that rates of fatal bleedings seen so far are not inconsistent with those seen in the RE-LY study". Boehringer concluded by saying that it will "continue to work with health authorities to ensure that usage of the product accurately reflects the label".