Upcoming events: Otsuka looks beyond Abilify and the HFSA meeting

Welcome to your weekly digest of approaching regulatory and clinical readouts. Phase III data are on the horizon from brexpiprazole, a project that Otsuka hopes will emerge as a successor to its blockbuster anti-psychotic Abilify, which is approaching the end of its patented life. Brexpiprazole has attracted impressive sales forecasts, but it will have to demonstrate clear differentiation for these to be realised.

Meanwhile the 17th Annual Scientific Meeting of the Heart Failure Society of America will take place on September 22-25. Alnylam impressed earlier this year with the first data on its amyloidosis product ALN-TTRsc, and details from the dose-escalation study will be presented. Meanwhile Cytokinetics will report more data from the Atomic-AHF trial of intravenous omecamtiv; the company has already said that the study failed.

Otsuka Holdings: brexpiprazole

Otsuka’s brexpiprazole, or OPC-34712, is being developed as an adjunct therapy for major depressive disorder. It is a close structural analogue of Abilify, the company’s biggest-selling product, and is said to exhibit reduced partial agonist activity at D2 dopamine receptors and enhanced affinity for specific serotonin receptors.

Two pivotal depression trials, Pyxis and Polaris, are due to end this year, having respectively recruited 826 and 1,650 patients. Both are testing brexpiprazole as an add-on to other antidepressant pills in patients who previously failed to respond to those pills. Three doses of brexpiprazole are being tested across the two trials, and the primary endpoint is change in Montgomery-Asberg Depression Rating Scale, a diagnostic questionnaire.

The most common adverse events seen in phase II were upper respiratory tract infection, restlessness, weight gain and nasopharyngitis.

While the results in depression will be the first real test of the drug, the bigger market for brexpiprazole is in schizophrenia, an indication for which data are expected in the first half of next year.

Plugging the hole

Brexpiprazole is forecast to become the Japanese company’s second-largest growth driver after the recently launched once-monthly form of Abilify; 2018 sales of the new pill are expected to reach $843m, according to EvaluatePharma consensus.

Alongside the once-monthly Abilify Maintena, brexpiprazole could go some way to filling the gap when Abilify comes off patent in 2015. Last year Abilify sales reached $5.3bn, a figure expected to shrink to $591m by 2018.

In 2011 Lundbeck paid $200m up front in a co-development and co-promotion deal for brexpiprazole and Abilify Maintena (Lundbeck and Otsuka tie the CNS knot, November 11, 2011). As such, the Danish company also stands to benefit from its success – Lundbeck will receive 50% of net European and Canadian sales for both products, 20% of net US sales for Abilify Maintena and 45% of net US sales for brexpiprazole.

While sales forecasts are nearing blockbuster status caution still lingers – JP Morgan analysts note a 30% chance of success in depression and just 20% in schizophrenia, citing “limited clinical differentiation in the data disclosed so far”. The project will need to change this opinion if it is to win market share from longer-acting drugs and generic forms of Abilify.

Heart Failure Society of America meeting, September 22-25, Orlando, Florida

In July Alnylam announced positive topline phase I data with ALN-TTRsc, intended to treat familial amyloidotic cardiomyopathy (FAC), a condition where misfolded TTR protein accumulates in the heart (Alnylam’s subcutaneous success drives shares to record high, July 12, 2013).

This trial showed an encouraging 80% “knockdown” of serum TTR protein levels in healthy volunteers, and at the HFSA meeting full-dose escalation results will be presented. An open-label phase II trial in 12 FAC patients will begin in the fourth quarter, followed by a pivotal phase III study next year.

Meanwhile Cytokinetics will present further data from the Atomic-AHF trial with intravenous omecamtiv. At the ESC meeting earlier this month the company said a single IV dose failed to have a significant effect on breathlessness in heart failure patients (ESC – Heart failure miss knocks wind from Cytokinetics, September 3, 2013). An imbalance of myocardial infarctions in the high-dose group was also seen, and investors will be watching the HFSA meeting for additional safety details.

Trial ID
Pyxis NCT01360645 
Polaris NCT01360632

All information is sourced to analyst notes and the EvaluatePharma Calendar of Events tool.

To contact the writer of this story email Joanne Fagg in London at joannef@epvantage.com or follow @JoEPVantage on Twitter

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