Eli Lilly will pursue no further development of its experimental Alzheimer's disease treatment solanezumab, the company announced this week, when it confirmed the drug failed to meet its primary endpoint in the Phase III EXPEDITION3 study.
What has effectively been labelled a near-miss for solanezumab could represent a worst-case scenario for the pharmaceutical sector and ongoing efforts to develop disease-modifying treatments for Alzheimer's disease. Analysts have been quick to suggest that a number of other drugs in late-stage development, all of which are targeting beta amyloid, as solanezumab does, are sufficiently differentiated from Eli Lilly's product. Expectation – or rather desperate hope – for some success therefore remains.
Indeed, some analysts have argued that as clinical findings "directionally favour" solanezumab, but have delivered only small magnitudes of treatment difference, this outcome can be viewed as an ideal result for those companies developing similar, but differentiated products; a view that will likely be met with considerable scepticism by many familiar with the development of drugs targeting beta amyloid over the past decade.
The biggest problem with beta-amyloid therapies currently in development is that they are not being prescribed early enough in the progression of Alzheimer's disease, argued Bernstein's Tim Anderson in a note to investors published on Wednesday. Eli Lilly recognised this in EXPEDITION3 by targeting 'mild' Alzheimer's disease patients, while drugs being developed by Biogen and Merck & Co. are targeting patients further 'upstream'; those with mild cognitive impairment.
This may still be too late. Anderson notes "the scientific consensus is that the ideal time to intervene is likely before there has been substantial amyloid deposition. Unfortunately, it is impractical to scan all patients for early signs of amyloid deposition, but equally worrisome is that just because a patient has such deposition, many will not develop Alzheimer's disease. What is really needed is a predictive biomarker of sorts that goes beyond amyloid imaging, capable of identifying what patients will highly likely progress to [Alzheimer's disease]. There is no such test that can do this so far."
Juno's quick fix could prompt lengthy investigation
There were some eyebrows raised in July when the FDA quickly overturned a clinical hold it had placed on Juno Therapeutics' CAR-T therapy JCAR015 just five days earlier. Two adults with acute lymphoblastic leukaemia (ALL) who had been treated with JCAR015 subsequently died from cerebral oedema. The addition of fludarabine to the pre-conditioning regimen was quickly identified as a potential cause for these deaths, but not everyone was convinced they were the only contributory factor. The FDA's decision to lift the clinical hold will now be scrutinised with Juno confirming on Wednesday that two further patients have died from cerebral oedema this week. Management said it was too early to provide a definitive outlook for JCAR015, but conceded that a decision could be made to terminate any further development.
New diabetes combos approved by FDA
Novo Nordisk and Sanofi both secured FDA approval for basal insulin/GLP-1 agonist combination products this week – to be branded as Xultophy and Soliqua, respectively – with launches planned in 2017.
Payers will play a key role in how these drugs perform, as will the pricing strategies implemented. Analysts expect Sanofi to price Soliqua at a modest premium to Lantus as a means to retain share for its basal insulin product as biosimilar competition emerges, while many expect Novo Nordisk to position Xultophy as a premium offering.
Whether Xultophy and Soliqua can significantly help to offset the pressures that Novo Nordisk and Sanofi are facing in the US diabetes market is another matter.
Consensus forecasts indicate combined sales of $1.5 billion for the two products in 2020, but feedback from both practising endocrinologists and key opinion leaders suggest that adoption of these combination products is likely to be determined by a higher-than-typical number of factors.
Amgen, Novartis deliver first Phase III data for CGRP inhibitor class
The future market for CGRP inhibitors – an emerging class of therapies to treat episodic and chronic migraines – could be worth between $5 billion and $10 billion, argue analysts. In presenting the first Phase III data for a drug in this class late last week, Amgen and Novartis now look poised to secure first-to-market status.
A number of competitor drugs are also in late-stage development, which will be music to the ears of US payers; in particular pharmacy benefit managers will enjoy scope to negotiate greater rebates in exchange for preferred formulary status, so analyst expectations should perhaps be considered with some caution.
We surveyed 160 physicians this week to better understand how they will utilise this drug class once available – see Physician Views Poll Results: 160-plus physicians provide feedback on new erenumab data and how they expect to use CGRP inhibitors for the treatment of migraine.
And don't miss…
Incyte CEO Hervé Hoppenot discusses the company's long-term growth plans and why a multi-therapeutic approach will be key to achieving success in immuno-oncology.
Cardiologists and primary care practitioners assess new data presented for Repatha at the recent American Heart Association (AHA) annual meeting and provide feedback on their expectations for the PCSK9 inhibitor class.
To read more Friday Five articles, click here.