Welcome to your weekly digest of approaching regulatory and clinical readouts. The amyloid beta hypothesis has been subject to significant stress testing in Alzheimer’s disease recently, and now upcoming data from TauRx Pharmaceuticals should reveal whether inhibiting aggregation of tau proteins could be a promising area of development.
Meanwhile, Novartis and MorphoSys should soon see phase II results for their macular degeneration antibody LFG316, which should be an important precursor to research into its use in combination with a second agent called CLG561.
Tau do you do?
The privately held TauRx, a Singapore-domiciled spinout using science developed at the University of Aberdeen, has pursued the thesis that tau protein accumulation in brain cells is the primary cause of Alzheimer’s disease and frontotemporal dementia. Most projects in late-stage development try to prevent the development of intracellular plaques consisting of accumulations of amyloid beta.
TauRx’s science is built around observations that the malaria drug methylthioninium chloride, or methylene blue, could dissolve tau tangles, and the group has sought to design a version of the compound that can be effective in neurological disease. LMTX is the second project from TauRx after Rember, which struggled to achieve bioavailability at a tolerable dose to have an effect on the disease; LMTX is reformulated to be tolerated at higher doses.
LMTX has been dosed in patients in three phase III trials, two in mild or moderate disease and one in behavioural variant frontotemporal dementia. The company last year said it had achieved the target enrolment in both Alzheimer’s trials, and was expecting the dementia study to complete enrolment early this year.
Data should be available in 2016, the company said – the clinicaltrials.gov file for the TRx-237-015 trial in mild and moderate disease lists a November 2015 primary completion date, and for TRx-237-005, in mildly affected patients, the date is April 2016. Because TauRx has no public investors it will not be legally obliged to disclose the data as a material event as soon as the analyses are complete, so it is difficult to predict when any findings might be revealed.
Novartis has rights to MorphoSys’s ocular antibody LFG316 as part of the two companies’ long-term research collaboration, and the project should soon have complete phase II data in the dry form of age-related macular degeneration (AMD), the more common form of the condition.
Novartis, of course, has annual sales of more than $2bn in wet AMD through its licensing of the Roche antibody Lucentis, but market share has gradually been chiselled away by off-label use of Avastin and the Regeneron/Bayer agent Eylea.
Dry AMD is a fairly open field by comparison. No specific treatments exist for the condition, although there are several candidates approaching late-stage milestones, including Roche’s phase III lampalizumab and Otsuka’s emixustat hydrochloride.
LFG316 is an anti-complement factor C5 monoclonal antibody in a 158-patient proof-of-concept trial testing two doses against placebo, to detect if the intravitreal injection can arrest the growth of geographic atrophy lesions. The study was to have completed in June.
Before making any calls on whether to initiate phase III, assuming the results are positive, the Swiss group might be awaiting analysis of a planned study pairing LFG316 with CLG561, which it acquired with the takeout of Alcon in 2010. That trial assesses CLG561 as a monotherapy as well as in combination; it is scheduled to start recruiting patients next month and conclude in 2018.
Ophthalmology has been a strength of Novartis’s, but its market share is forecast to shrink by nearly half between 2014 and 2020, and the group will fall behind Allergan in this therapy area. The Alcon division’s weak performance has been a drag on Novartis this year as its sales were flat, so eyecare could do with some rejuvenation. However, if the Swiss company is looking to LFG316 and the rest of its pharma pipeline to revive sales, it could be waiting a while.
|LFG316||Monotherapy in dry AMD||NCT01527500|
|With CLG 561 in patients with geographic atrophy||NCT02515942|