West Coast Editor

Quicker, easier relief for migraine headaches could be near, thanks to Alexza Pharmaceuticals Inc.'s aerosol version of the oft-used intravenous drug prochlorperazine, AZ-001, which yielded positive data in a 440-patient, Phase IIb study.

All doses of the drug - 5 mg, 7.5 mg and 10 mg - hit the primary endpoint of two-hour pain relief compared to placebo, when delivered by way of Alexza's Staccato device. Pain was reported using the International Headache Society's 4-point scale.

Alexza's stock (NASDAQ:ALXA) soared 52.4 percent on the news, closing Monday at $15.21, up $5.23.

Thomas King, president and CEO of Palo Alto, Calif.-based Alexza, said the company is aiming for an end-of-Phase II meeting with the FDA around the middle of next year, after more studies are done to explore pharmacokinetics and longer-term animal toxicity.

"Our hope would be to go to that meeting with our partner or partners," King told BioWorld Today, and talks with candidates are under way.

AZ-001 showed statistically significant improvements in pain response in 66 percent of patients at the 10 mg dose (p=0.0013), 63.7 percent at the 7.5 mg dose (p=0.0046) and 60.2 percent of those at the 5 mg dose (p=0.0076), compared to 40.8 percent of patients given placebo in the Staccato device.

The news got even better when Alexza checked other efficacy endpoints. In pain-free response (PFR) at two hours (where the patient reports an IHS score of zero), 35 percent of patients at the 10 mg dose gained relief (p=0.0019) and 29.7 percent reported no pain at the 7.5 mg dose (p=0.0226), although the 5 mg dose, at 21.4 percent, did not reach statistical significance compared to placebo. The rate of pain-free response at two hours in placebo patients was only 15.3 percent.

Sustained PFR, in which the patient reports no pain for up to 24 hours, was gained in 30.1 percent and 23.1 percent of total patients in the 10 mg and 7.5 mg dose groups, respectively, whereas placebo totaled 10.2 percent.

Approved for nausea and vomiting and sold under various trade names in several forms, prochlorperazine is under development in buccal tablet form by BioDelivery Sciences International Inc., of Morrisville, N.C., though the FDA found the product not approvable early last year.

Pivotal studies with AZ-001, King said, will include varying doses given to individual patients over a period of time, and work done ahead of Phase III trials will seek more information about the drug's efficacy against such migraine symptoms as photophobia, phonophobia, nausea and vomiting.

"Certainly people get a significant amount of nausea, but it turns out the incidence of vomiting in migraine is quite low," King said, so Alexza hopes to either negotiate the vomiting endpoint with the FDA or limit the size of the study, especially since the compound already is approved in another form for that indication.

Migraine is a popular target. Last week, Chapel Hill, N.C.-based Pozen Inc. won FDA acceptance for review of its amended response to the agency's approvable letter asking for more safety data related to Trexima, Pozen's combination of sumatriptan succinate and naproxen sodium. (See BioWorld Today, June 6, 2006.)

Earlier this month, the FDA said it would take three more months to review the supplemental new drug application for Frova (frovatriptan succinate) in 2.5 mg tablets for the expanded indication of short-term prevention of menstrual migraine. The drug is partnered with Vernalis plc, of Winnersh, UK.

Alexza also reported positive Phase IIa data with another Staccato-delivery drug: AZ-004 (loxapine) for schizophrenics with acute agitation. The 10 mg dose met the primary endpoint of reduced agitation from baseline to two hours after dosing, compared to placebo.

"The number of patients is smaller [for AZ-004 than for AZ-001] but the repeat use is probably larger," King said. "It's not for the patient who shows up in the emergency room in an uncontrolled fit of agitation." Instead, AZ-004 is for those who take a "drug holiday," as schizophrenics are prone to do once or twice a year, causing their symptoms to spiral out of control. AZ-004 would be used while anti-psychotic drugs are re-started and taking effect, he said.

Alexza went public last year, selling 5.5 million shares at $8 per share, for gross proceeds of $44 million, lower than the $10 to $12 range set earlier (which would have pulled in $60.5 million at the midpoint), and is just more than half of the $86.25 million anticipated when Alexza filed for the initial public offering the year before. (See BioWorld Today, Dec. 27, 2005, and March 6, 2006.)

Of 400 generic drugs screened, Alexza has found 200 with which the aerosol delivery system could work.

"We don't need billion-dollar drugs to make this [business] model successful," King said, noting that the company doesn't need to find indications with potential beyond $150 million or so, since the cost of development is lower than for new entities.