Ionsys approval should be no balm for AcelRx’s pain

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The bad news on AcelRx Pharmaceuticals' sublingual post-surgical pain relief project Zalviso has got worse, with the FDA refusing even to talk to company executives about a regulatory submission based on existing data.

Last week’s approval of a similar product in the form of the Medicines Company’s Ionsys is instructive regarding the problems ahead for AcelRx. The Ionsys transdermal delivery system had been treated roughly a decade ago when it was in the hands of Johnson & Johnson, demonstrating just how safety-conscious the agency is when it comes to opioids, no matter how they are delivered.

Down while the market is up

AcelRx’s shares today plunged 28% to $3.02, a 30-month low, after yesterday’s post-market disclosure of the FDA’s meeting refusal. On the year the group has lost 52% of its value, a sharp contrast from the 13% gain for the Nasdaq Biotechnology Index.

The announcement was bad news on bad news, as the FDA had already told the California-based group that an additional trial would be necessary; layoffs calculated to save $900,000 per quarter and the departure of chief executive Richard King followed that revelation (AcelRx hits the brakes on submission and plans new trial, March 10, 2015).

AcelRx contends that it already has the necessary data to show low rates of medication error and inadvertent dosing to address the FDA’s concern about misuse of Zalviso, which combines small sufentanil tablets with a handheld device to deliver a single dose no more than once every 20 minutes to hospital patients.

Declining the meeting request was a clear sign that the FDA is not interested in hearing any more about these data, though the group still held out some hope of pursuing dispute resolution options to avoid the expensive prospect of another clinical trial.

Given that its follow-on project ARX-04, a single-use sufentanil tablet dispenser, has just entered phase III, AcelRx has good reason for wanting to avoid an additional pivotal trial for Zalviso that would probably require some 200 to 400 patients.

The group had $64.4m in cash at March 31; in 2012, when it had three Zalviso studies under way with more than 900 patients enrolled, R&D expenses alone were $25m. In its first-quarter SEC filing AcelRx said it had enough cash to fund operations through the first half of 2016, though a large-scale clinical trial, if required by the FDA, would leave a funding gap.

Learning from Ionsys

The approval of Ionsys, meanwhile, should not necessarily be taken as a good sign for Zalviso. For one, Ionsys is playing in the same space as Zalviso – replacing intravenous analgesics in the post-surgical setting – in the Medicines Company’s case via an electronic patch.

Another point is that Ionsys was approved by regulators on both sides of the Atlantic in 2006, though only on the second pass in the US. Flaws in the delivery device caused its withdrawal in the EU and a failure to launch in the US. J&J sold it to Incline Therapeutics, which was then acquired by the Medicines Company, and it is forecast to join the same group's Orbactiv and Raplixa as a steady earner in the $100-200m range.

It took five years from Incline’s takeover of Ionsys until this latest approval, thanks to the FDA’s demanding evaluation.

The lesson for AcelRx is that it usually takes time and persistence to persuade the FDA when it comes to anything involving opioids. The M&A scenario, involving a bargain-minded buyer with plenty of patience, is a best case. The more likely outcome is for AcelRx’s late-stage sufentanil pipeline to spend quite some time in regulatory limbo, necessitating a dilutive fundraising.

To contact the writer of this story email Jonathan Gardner in London at jonathang@epvantage.com or follow @ByJonGardner on Twitter

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