The FDA advisory committee verdict on Alexza Pharmaceuticals’ Adasuve – nine voting in favour of approval, eight against and two abstentions - is a long way from a ringing endorsement of the product.
Despite this, the 40% rise in the company’s share price this morning suggests there are a few investors willing to make a call on the product’s chance of reaching the market - having halved in value to a record low of 51 cents on Thursday the stock is probably cheap enough to persuade some to take a punt. Due by February 3, the FDA’s final verdict is not far away but given the safety concerns raised at the panel hearing, approval will come as a major surprise.
That Adasuve represents an effective, novel and quick way to calm agitation associated with schizophrenia and bipolar disorder has never really been in question. An inhaled version of loxapine, the formulation works in a matter of minutes compared to 15 minutes or longer for injected versions of the widely used drug. Eliminating needles – for the benefit of both doctor and patient – has also been promoted as a benefit by the company.
Exacerbation of respiratory conditions has always been the worry, given safety signals seen in clinical trials, such as bronchospasms in asthmatics. Given the difficult and fractious circumstances in which this drug is likely to be used, the regulator has raised concerns that these at risk patients might be hard to identify and therefore reducing safe use of the drug – hence the complete response letter last year.
The verdicts of yesterday’s panel delivered as answers to a series of questions will not make the regulator’s job much easier. The fact the experts were only able to half-heartedly endorse a REMS programme and dosing regimen that was much stricter than that proposed by Alexza makes it more likely the FDA will err on the side of caution.
Asked whether the drug has been shown to be effective as a treatment for agitation in patients with schizophrenia or bipolar mania, 17 voted yes and only one no.
However when asked whether Adasuve has been shown to be acceptably safe when used in conjunction with Alexza’s proposed REMS, the vote was an almost emphatic no by 17 members – one voted yes. A stricter REMS proposed by the FDA was viewed as slightly more acceptable with five voting yes, 12 voting no and one abstaining.
At this stage the panel was asked to vote on the “acceptable” safety of a much more restricted regimen – the FDA’s REMS and a single dose in 24 hours; Alexza has applied for a label permitting repeat dosing. This elicited the most positive response from the panel, with 11 voting in agreement, five disagreeing and two abstaining.
However the final question on whether approval should be granted in this restricted regimen saw the risk-benefit ratio swing back. Nine yes and 8 no votes, with one abstention, means the Adasuve filing failed to convince the experts of the product’s worth. It is hard to see how the FDA could come up with a more definitive opinion, so an outright rejection and potentially a request for further data seems the most likely outcome now.
Running out of room
Surprises happen of course. Only last month the FDA gave a green light to Transcept Pharmaceuticals’ middle-of-the-night insomnia pill Intermezzo, in spite of concerns that lingering effects might cause safety issues the next morning (Intermezzo approval not the end of Transcept thriller, November 24, 2011).
And who can forget Fanapt, the schizophrenia drug that was approved in 2009 amid much regulatory hand-wringing over what additional benefits the drug offered over existing and very similar therapies (Vanda shares rocket after surprise Fanapt approval, May 7, 2009).
Both these examples offer hope for Adasuve, illustrating that the FDA can get past real concerns about safety and risk-benefit. However there are also many cases of tortuous and fruitless attempts to win regulatory blessings, at big and small companies. Only a few months ago Eisai abandoned attempts to get an extended release version of its blockbuster PPI Aciphex on the market in the US, after the regulator demanded new trials.
With only enough cash to last until the second quarter of 2012, Alexza is running out of wriggle room.