Potential catalysts in the third quarter of 2015 include decisions by the US Food and Drug Administration (FDA) on the approval of sebelipase alfa (developed by Synageva) for lysosomal acid lipase (LAL) deficiency and of cobimetinib (developed by Roche) for melanoma. In addition, Biogen will present updated results from a widely watched Phase Ib study of aducanumab for mild/prodromal Alzheimer disease.

Sebelipase alfa is a recombinant form of LAL intended to reduce the build-up of cholesteryl esters and triglycerides in patients with LAL defiency, a rare inherited lysosomal storage disorder. The pivotal ARISE study of sebelipase alfa demonstrated the normalization of levels of alanine aminotransferase — the study's primary end point and a marker of liver injury — and significant reductions in secondary end points such as the levels of triglycerides. With no competitors in this orphan indication, FDA approval is anticipated by the Prescription Drug User Fee Act (PDUFA) action date on 8 September.

Also heading towards a likely FDA approval is Roche's MEK inhibitor cobimetinib, for which the PDUFA date is 11 August. Positive results have been disclosed from the Phase III coBRIM study of cobimetinib in combination with vemurafenib (Zelboraf; Roche), a BRAF inhibitor that was approved by the FDA in 2011. In this study, which involved 495 BRAF-inhibitor-naive patients, a significant increase in progression-free survival was observed for the cobimetinib plus vemurafenib combination compared with vemurafenib alone (9.9 months versus 6.2 months). If approved, the cobimetinib–vemurafenib combination will probably help bolster Roche's presence in the BRAFV600-mutant segment of the melanoma market, and offer an alternative to Novartis' trametinib–dabrafenib combination, which was approved for BRAFV600-mutant melanoma in 2014. The use of cometinib could eventually expand into a broader population if results from a Phase II trial in combination with bevacizumab and a Phase II trial (known as coBRIM-B) in patients with melanoma brain metastases are positive.

In March, Biogen announced positive results from a pre-specified interim analysis of a Phase Ib study of aducanumab, an amyloid-β-specific monoclonal antibody. This study enrolled 166 patients with mild/prodromal Alzheimer disease and tested three doses of aducanumab (3 mg, 6 mg and 10 mg per kg) compared with placebo. Significant effects on two end points — the Mini Mental State Exam (MMSE) and the Clinical Dementia Rating Sum of Boxes — were observed for the 10 mg per kg cohort, and for the MMSE end point for the 3 mg per kg cohort, but are preliminary given the small patient numbers (~30) per cohort. Positron emission tomography imaging using florbetapir also revealed significant reductions in amyloid plaques in the brain. Whether these effects are in fact dose-dependent remains to be seen from additional data from the 30 patients in the 6 mg per kg cohort, which are due to be announced at the Alzheimer's Association International Conference in July. However, Biogen has already reported that it intends to bypass Phase II studies and directly test aducanumab in Phase III trials in the second half of the year.