Upcoming events: US decisions on Movantik and Otezla

Welcome to your weekly digest of approaching regulatory and clinical readouts. The US regulator will deliver verdicts on Movantik for opioid-induced constipation in non-cancer pain and Otezla for psoriasis by September 16 and 23 respectively.

Movantik could become the first oral Mu opioid receptor antagonist approved worldwide for that indication, but the real opportunity comes with combining it with opioids to create a painkiller that does not cause constipation in the first place. Meanwhile, psoriasis would be a much bigger application for oral Otezla compared with its current use in psoriatic arthritis. However, clinical results have not been impressive, and the drug could have trouble finding a place, even in a market dominated by injectables.

AstraZeneca/Nektar Therapeutics: Movantik

Movantik, known generically as naloxegol oxalate, is a peripherally acting Mu opioid receptor antagonist (Pamora). In June the FDA's advisory committee discussed the potential cardiovascular risks associated with this class and the necessity for outcomes trials to support approval.

The committee suggested post-approval data collection for cardiovascular safety rather than outcomes trials, a positive outcome for developers that prompted Nektar’s shares to jump 11% (Panel backs novel constipation class but the blockage will be hard to remove, June 13, 2014). In phase III trials of Movantik major cardiovascular events were no more common than with placebo. 

If approved Movantik would be the first once-daily oral Pamora for non-cancer pain. The injectable Relistor, another Pamora, was launched in 2008, but is only approved to treat very sick patients receiving palliative care – typically cancer patients.

However, a PDUFA is set for Relistor on September 29 for chronic non-cancer pain, and an oral version is in phase III.

Co-formulation

By 2020 Movantik is set to lead the market, according to consensus forecasts from EvaluatePharma, with $241m in sales. Injectable Relistor's 2020 forecasts are at $134m, while its oral version has consensus expectations of $155m.

AstraZeneca licensed worldwide rights from Nektar in 2009, and will pay Nektar royalties. Analysts at JP Morgan are well above consensus, forecasting 2018 royalty payments of $152m.

The analysts note that while Astra has already started commercial preparation, a launch would not occur until late in the first quarter or early in the second quarter of next year, as the drug has to go through the DEA scheduling since it is an opioid; the company does not expect it to be scheduled.

The real win for Nektar, however, would come if the drug could be co-formulated with opioids, creating a single-pill opioid painkiller that does not cause constipation. The products in this co-formulation programme, which is known as NKTR-119, are also licensed to Astra.

Celgene: Otezla

Otezla (apremilast) is already on the US market for psoriatic arthritis, for which sales by indication data from EvaluatePharma forecast $207m in 2020 revenue.

But psoriasis is a much bigger indication for the PDE4 inhibitor, with $894m sales for that year. Indeed, Otezla is Celgene’s second-biggest growth driver, behind its multiple myeloma treatment Revlimid.

While it gained approval in psoriatic arthritis, beyond its oral dosing and favourable side-effect profile Otezla is generally less efficacious than injectable incumbents (After US green light, Celgene’s Otezla has it all to do, March 24, 2014).

Psoriasis is itself a highly competitive field, where biologicals lead the way. While Otezla showed statistical effects in primary and some secondary endpoints in psoriasis trials, questions remain over where it will fit into treatment protocols. There is a possibility that it will serve as a bridge between the cheap but less effective first-line therapy methotrexate and expensive antibodies like Stelara.

Celgene will have to work hard to pitch Otezla’s oral dosing as an advantage. Hot on its heels is Novartis’s secukinumab, an IL-17 antibody delivered via a prefilled syringe and autoinjector. Secukinumab is due an FDA decision in early 2015, with an advisory committee meeting scheduled for October 20.

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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