Vanda Pharmaceuticals reported positive Phase III data June 26 for its sleep disorder compound tasimelteon (VEC-162) from a study in chronic primary insomnia in adults. The compound, licensed from Bristol-Myers Squibb in 2004, met the primary endpoint for immediate and short-term improvement of sleep onset.

A novel melatonin receptor agonist, tasimelteon also is being investigated in circadian rhythm sleep disorders, transient insomnia and mood disorders related to sleep difficulties, such as depression. Vanda previously has stated that CRSD likely will be the key to the drug's differentiation in the marketplace because FDA has never approved an insomnia drug for CRSD (¹ Also see "Vanda Moves Ahead With Development Of Iloperidone, VEC-162" - Pink Sheet, 1 May, 2007.).

During a June 26 investor call on the new data, Vanda CEO Mihael H. Polymeropoulos said, "The differentiation of this compound based on its ability to uniquely modify ... circadian rhythm sleep disorders can be a very interesting angle of first approach to the market."

With previous Phase III success in transient insomnia, Rockville, Md.-based Vanda has no plans to initiate further studies on the compound, but now will look to discussions with FDA to determine what other trials will be needed to proceed to filing an NDA. During the call, Vanda said it expects to begin new trials approved by FDA in late fall, with the hope of completing all such studies by 2010.

For chronic insomnia, Polymeropoulos predicted Vanda would need to conduct at least one more 12-week study in adult patients and perhaps another in elderly patients before it could file for that indication. He also expects FDA will require further work in CRSD.

Further work to show maintenance of tasimelteon's effect over a longer term probably will be another key for marketing, Polymeropoulos noted, because current market leader Ambien (Sanofi-Aventis' zolpidem) does not include sleep-maintenance effect on its label.

Other market competition could come from Takeda's Rozerem (ramelteon), another melatonin receptor agonist. Vanda, however, contends its compound works through a different mechanism of action, binding to MT1 and MT2 receptors equally, while Rozerem preferentially binds to the MT1 receptor.

Vanda has been seeking a commercialization partner for tasimelteon. Other than saying discussions are ongoing with many companies, Polymeropoulos did not elaborate during the June 26 call how those efforts are proceeding.

"To execute a true development plan in circadian rhythm disorder, we would need additional resources, and whether this comes from additional financing, partnership, etc., [is] a different story to tell," he admitted.

Results show improved sleep onset

The Phase III chronic insomnia trial tested 322 adult subjects. Each patient was randomized either to a 20 mg or 50 mg dose of tasimelteon or placebo. The primary endpoint measured immediate (night one) and short-term (night eight) ability to improve sleep onset on the basis of latency to persistent sleep.

Mean LPS at baseline was 78.8 minutes in the 20 mg group, 76.4 minutes in the 50 mg group and 78.2 minutes in the placebo group, Vanda said. Averaging nights one and eight of treatment, LPS improved by 45.0 minutes in the 20 mg group (p<0.001), by="" 46.4="" minutes="" in="" the="" 50="" mg="" group=""><0.001), and="" by="" 28.3="" minutes="" in="" the="" placebo="">

Averaging nights 22 and 29 of treatment, LPS improved by 49.4 minutes with the smaller dose (p<0.001) and="" by="" 45.1="" minutes="" with="" the="" larger="" dose="" (p="0.016)," while="" the="" placebo="" effect="" was="" a="" 33.9="" minute="" improvement,="" vanda="">

Improvement was seen with both treatment doses in the first night of treatment, the company added, with LPS occurring 22.9 minutes faster with a 20 mg dose (p<0.001) and="" 25.9="" minutes="" faster="" with="" 50="" mg=""><0.001), compared="" with="">

To measure sleep maintenance, the study also evaluated secondary endpoints for total sleep time and wake after sleep onset. Night one and eight average in the 20 mg group showed 51.4 minute total sleep time improvement, along with 52.0 minute improvement in the 50 mg group. However, control arm patients improved by 40.0 minutes.

Night one and eight average improvement in wake after sleep onset was 12.2 minutes with the smaller dose and 14.1 minutes with the larger dose, compared to 11.7 minutes in the placebo arm.

In a June 26 note on the new data, David Ansellem of FBR Capital Markets wrote: "We believe tasimelteon can be approved with only a sleep onset claim, but given that efficacy in sleep maintenance has yet to be clearly demonstrated, it is not evident to us if this will be attractive to possible partners."

Ansellem projects a 2011 launch for tasimelteon, with $16.1 million in U.S. sales that year ($16 million in the U.S.) and $113.6 million in worldwide sales in 2012 ($103.3 million U.S.).

Vanda awaits FDA action on iloperidone NDA

Vanda had $77 million in cash on hand as of its first-quarter 2008 financial data report May 1, which Polymeropoulos says is sufficient to last through the firm's planned activities this year. A key milestone for the company this year is FDA's late July action date for the iloperidone NDA, its atypical antipsychotic for schizophrenia (² Also see "Encouraging Phase III Data Reported For Vanda’s Schizophrenia Candidate" - Pink Sheet, 13 December, 2007.). Approval and a relatively quick launch likely would mean sales revenues starting next year.

A June 26 analysis by Ansellem projects $37.7 million in sales revenue for iloperidone in 2009 (all U.S.), growing to $356.3 million in 2012, with some ex-U.S. sales.

-Joseph Haas (j.haas@elsevier.com)

Vanda Reports Strong Phase III Data For Sleep Disorder Candidate In Chronic Insomnia

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