U.S. Youth Suicide rates spike in 2004

After declining U.S. youth suicide rates from 1996 to 2003, the numbers increased 14.5 percent in 2004. A Carnegie Mellon statistics professor is trying to understand why. Dr. Joel Greenhouse says the jump was first looked at as an statistical anomaly. Common risk factors such as substance abuse and the use of firearms have not changed in 10 to 19-year-old youths.

However, one possible influence is the Food and Drug Administration's "black box" label on antidepressants, initiated in 2004. Others include the increased use of internet social networks and increases in suicide among U.S. troops. Suicide statistics declined in 2005, but Dr. Greenhouse says those rates are still well above the previous regression.

McCrory, Obama, and Charlotte

In 2004 Mike Easley won the vote in the 8th and 10th Congressional Districts, both dominated by the Charlotte media market, by an average of 6%. He did so even as John Kerry lost them by an average of 23 points to George W. Bush. In other words Easley outran Kerry by 29%.

This year it's a completely different story. Barack Obama appears primed to do much better in these two districts than Kerry did. He currently trails in them by an average of 11 points. For Bev Perdue the news is not so good. Pat McCrory has an average 14% advantage.

The reason McCrory is doing so much better than Patrick Ballantine did here is a strong standing with white Democrats. In our June 10th District poll Perdue led just 56-32 among voters in that demographic. The 8th District survey we released yesterday had Perdue up 57-31 with them. It is not a stretch to think Mike Easley won support from 80% or more of these voters in his runs for Governor.

McCrory's overwhelming appeal in the greater Charlotte area is the reason this race is so competitive in a Democratic year. The Perdue campaign is either going to have to effectively take the shine off McCrory's moderate veneer to turn the Democratic and independent voters in that region back into her column, or she's going to have to rely on Obama's machine bringing out exceptional turnout in the other urban centers of the state.

You know it's a new world order in North Carolina when the Democratic gubernatorial candidate, rather than running away from the Presidential nominee, may need his help to be elected.

As for Obama, his improved poll numbers in these districts show that it's an oversimplification to think his success is completely reliant on increased black turnout. The 10th District has a minuscule minority population yet Obama is running about ten points better there than John Kerry did. As the economy becomes a bigger and bigger issue in voters' minds, more are moving toward supporting the Democrat for President, white or black.

We are going to have three very competitive statewide races this fall.

Pfizer Snaps Up Dimebon

This morning, Pfizer announced that it’s paying $225 million in cash upfront and up to $500 million in development milestones, plus assuming 60% of the development costs and commercialization expenses, in exchange for a 60% share of the profits of Medivation’s dimebon, a potential treatment for Alzheimer’s Disease and Huntington’s Disease. Medivation, in addition to retaining a 40% share of the reward and the risk, also gets a US co-promote and a royalty ex-US.

The deal is not surprising given Pfizer’s recent Alzheimer’s forays. The pharma bought Rinat Neuroscience in 2006 mostly to have a large-molecule play that would round out its AD portfolio--an antibody in early-stage development now known as PFE360365 that binds Abeta peptide, one of the hallmarks of the disease. Around the same time, Pfizer also inked a deal with TransTech Pharma on a dual-mechanism antagonist of RAGE (receptor for advanced glycosylation products), a molecule that both binds Abeta peptide and may also reduce the neuro-inflammation seen in AD.

Dimebon is significantly more advanced that the Rinat and TransTech compounds, but the collaboration with Medivation isn't all that expensive in comparison with the price tag of other Pfizer late-stage partnering deals, including that apixaban deal we've talked so much about lately. It also tops the numbers on the other recent deal for one of the few late-stage AD drugs—Lundbeck’s ill-fated spend on Myriad’s Flurizan in May 2008, which included $100 million upfront. Flurizan’s development was discontinued in June after its Phase III trial failed to show any difference between treated patients and the placebo group.

Dimebon also fits the Pfizer portfolio because it differs from most of the late-stage approaches to AD, which are based on modulating the so-called amyloid cascade. The amyloid hypothesis posits that deposition of amyloid beta (Abeta) peptides and the formation of amyloid plaques in the brain are early events that trigger subsequent ones such as neurodegeneration and the formation of the neurofibrillary tangles that can destroy nerve cells and neurons.

Abeta-targeting drugs include Flurizan, the Wyeth Phase III antibody bapineuzumab, and Lilly’s two late-stage AD candidates, the gamma-secretase inhibitor LY450139 and the Abeta antibody LY2062430, whose ultimate development Lilly recently decided to share with TPG-Axon and NovaQuest (the partnering arm of CRO Quintiles), in order to hedge the clinical risk.

The data on a completed Phase II/III trial of dimebon in Russia, which got considerable play at this year’s International Conference on Alzheimer’s Disease (ICAD) in late July, had been previously reported. But the context of Flurizan, disappointing Phase II data on bapineuzumab reported in June and further discussed at ICAD (a highly anticipated explanatory presentation that did nothing to assuage doubters), and even Lilly’s seeming bail-out on its candidates (the antibody data, less noticed than bapineuzumab certainly, remain tantalizing) could only have bolstered Medivation’s bargaining position.

Dimebon also appears to be the only late-stage AD drug candidate with a shot at potentially improving disease symptoms, as opposed to delaying progression of the disease, as is the hope with other putative disease modifying AD agents in development including the Abeta targeting compounds.

The completed Phase II/III study of dimebon was a 26-week trial, with an added blinded open-label six-month extension. More than 80% of the patients decided to stay on, giving the investigators an extended look at both the drug and placebo groups.

They determined that patients given dimebon were significantly improved compared with baseline and compared to those taking placebo, for all five of the designated outcome measures including assessments of cognition, function, and behavior. The primary analysis showed a significant drug-placebo difference in change from baseline on the ADAS-cog (a cognition scale), which was similar to the difference seen in the fully evaluable population at week 26. The improvements “were evident to clinicians assessing global function (CIBIC-plus), which supports the relevance of the treatment effect,” the investigators wrote in the report on the trial in the July 19, 2008, issue of The Lancet.

Moreover, they concluded that the drug-placebo differences were not just driven by worsening of the placebo group: there was actual improvement, which also increased substantially at week 52 compared with week 26, “suggesting that benefits continue to increase with time,” they said. “The continued and increasing benefit of dimebon over the course of the study is especially important because at present no approved therapies for mild-to-moderate Alzheimer’s disease have shown increasing improvement over 12 months,” they added.

At a time when many AD drug developers are content with running Phase II trials focused more on confirming mechanism than on showing efficacy, dimebon stands out. Despite the fact that it was done on a shoestring budget, the Phase II Russia trial was designed to be potentially pivotal, according to Rachelle Doody of Baylor School of Medicine, a consultant to Medivation who was instrumental in its planning. (Doody was also the lead clinical investigator in the development of Aricept, the AD drug marketed by Pfizer and Eisai.)

If an ongoing dimebon Phase III study, set for completion in 2010, meets its endpoints, Medivation (and now Pfizer) may even be able to piggyback the Phase II study as a second pivotal trial. The investigators did the study with English reports forms and “all the things that would be required for FDA audit,” she says. “We are fully prepared to have FDA audit it. [We were] never expecting we would get it, but were being ready just in case.”

The theme of ‘what can you know and how can you know it’ in Phase II is critical in AD drug development, and is the focus of a feature article set for the upcoming issue of IN VIVO (out next week!), based largely on discussions at ICAD about the perils of late-stage clinical trial design in AD. For purely selfish reasons, we wish Pfizer had waited to announce the deal. It’s already too late to amend it in the context of the Pfizer deal. (Woe is us.) And since the article didn’t make it to print before the deal, it’s also too late for us to sound all that prescient. But for what it’s worth, the piece touches on dimebon in its conclusion, as follows:

Perhaps the greatest cause of excitement at this year’s ICAD centered on Medivation’s dimebon, which in a Phase II study conducted in Russia was safe and appeared to improve the clinical course of patients with mild to moderate AD. The drug’s potential in AD was first identified by screening known compounds for dual activity against the cholinesterase and NMDA receptors—its mechanism of action is still being debated--and dimebon is now lined up to begin a pivotal Phase III study. If the new study meets certain endpoints, the FDA has said it would accept an application for approval with the completed Phase II as a second pivotal study—a testament to that study’s design and conduct.

That’s encouraging news for the field... But at the same time, the serendipitous nature of dimebon’s discovery as an AD drug has led some to lament that, in terms of discovery approaches, it may be the best they can do. No wonder Pharma is hedging its bets.

The theme of serendipity is worth reprising here—it goes a long way to explain Pfizer’s portfolio strategy in AD and the price it needed to pay for a competitive asset like dimebon. In fact, there’s no consensus on the mechanism underlying AD: it could be Abeta, aggregation of the Tau protein that causes neurofibrillary tangles, and/or some co-factor such as oxidative stress or the consequences of a build-up of calcium in the brain. In the words of one company’s clinical director, “If there was one mechanism we were sure would work, everybody would be working on it.”

Oh, and congratulations to Medivation's president David Hung, who purchased the patent on dimebon, an antihistamine that was put on the shelf after Claritin hit the market.

Specter on McCain's Chances in PA

Pennsylvania's senior U.S. Senator Arlen Specter says the Republican Party has a "little healing" to do at its convention in St. Paul, Minnesota. Specter told DUQ that the whole party has to pull together but in order for John McCain to win, the Republicans must appeal to independents and Democrats. Specter says he has high regard for Democratic Presidential nominee Barrack Obama whom he calls "a phenomenon as an orator and campaigner" but he says it comes down to McCain's experience. Specter says both McCain and Obama have a shot at winning Pennsylvania and he believes the four suburban counties around Philadelphia could be key to a McCain victory in Pennsylvania.

PA Sends Help to Gulf Coast

Emergency and rescue workers from Pennsylvania are in Louisiana and Mississippi this week as the Gulf Coast rebounds from Hurricane Gustav.
The state Bureau of Emergency Services sent 250 people and 60 ambulances to help.
Before Gustav hit, Pennsylvania Strike Team members evacuated patients from Louisiana hospitals. Then, while Gustav touched down on Monday, the group took shelter about four hours away. Joe Schmider directs the Pennsylvania E-M-S. He says Tuesday the emergency workers moved on to Thibodaux, a small bayou city in southeastern Louisiana.

"Where they are going to triage, transport and treat patients that are coming in. They are setting up and waiting on patients coming in. There is a command system down there and they are apart of that, this is their mission right now to set this receiving center up."

He says Gustav's force and damage was far less than predicted, so it's unclear how many patients will need the care, medication and natural-disaster assistance the team is trained to provide.
Schmider says the effort will cost about 2 million dollars, money that will likely be reimbursed after Louisiana receives federal assistance.
A Pennsylvania-based -- federal urban search and rescue team is also in the Gulf Coast, helping out in Pearl, Mississippi.

PHOTO GALLERY: ACT LABOR DAY CLASSIC 200 THUNDEROAD SPEEDBOWL Aug. 31, 2008 by M.P. Roy

This is a 443-photo gallery from Thunderoad Speedbowl in Barre, VT, on Sunday, August 31, 2008, featuring the American-Canadian Tour (ACT) 'Bond Auto Labor Day Classic 200'. Thanks to M.P. Roy for the photos. You can see M.P.'s website here.

Scotia Speedworld: Two to go for weekly racers

HALIFAX, NS (September 2, 2008) - If we were at the track we would see the flags the stock car racing community call "popsicle sticks" - which would indicate to both racers and fans that this Friday night's show at Scotia Speedworld marks two-to-go for the 2008 Lockhart Truck Centre Weekly Racing Series season.

 

With a rain-out last week cancelling their show, all six weekly racing divisions are fired up and ready to roll this week, including the C&R Auto Supply Sportsman, the Wallace Equipment Hobby Stock, the Miller Tire BFGoodrich Thunder & Lightning divisions, the Legends Cars and the Sojourn Signs Bandoleros.

 

With just two races remaining to determine final standings for all six classes, the pressure will be on this week as each of the over 100 drivers that compete in Scotia Speedworld's weekly racing series are chasing points that will determine championships, rookie titles, numerous other season-ending awards and ultimately the final point standings which often-times set the stage for the next years racing program.

 

A good race - or a bad one - could determine who clinches their respective titles next weekend in the season finales at Scotia Speedworld. Division point leaders include: Terry Roma (sportsman), Mike Alexander (hobby stock), Derek MacCallum (thunder cars), Andrew Starks (lightning cars), Ian Mollins (legends cars), Dylan Blenkhorn (bandoleros). With the exception of Roma, the other five racers are potential first-time Scotia Speedworld champions.

 

Due to popular demand, the Kiddies Rides that were rained out last week have been moved to this week - a chance for children to get a ride in a racecar with their favourite Lockhart Weekly Racing Series driver. This week's show is the last one for '08 where all six divisions will be on the race card. Next week (September 12 & 13) there will be two big nights of championship racing action at Scotia Speedworld.

 

The Kiddies Rides start this Friday night at 7 p.m. with racing at 7:30. The grandstand gates and box office will open at 5:30 p.m.  Fans should note the Bandolero heat races will have a special start time of 6:30 p.m. this week in order to accommodate the Kiddies Rides at 7 p.m.  Grandstand admission this Friday night is just $12 for adults and $2 for youth aged eight to 15.

 

Tickets are now available for the big season finale weekend at Scotia Speedworld. Special savings two-day tickets are just $30 for adults and $5 for youth aged eight to 15. Advance tickets can be purchased at Ticket Atlantic (grandstand only; two-day and/or September 13 only; adult and youth). These tickets as well as pit passes ($40/two days) will also be available at the gate on September 12 and 13. Children seven and under are admitted free at Scotia Speedworld, when accompanied by an adult.

 

About Scotia Speedworld : Scotia Speedworld is a 3/10-mile asphalt oval stock car racing track featuring the Lockhart Truck Center Weekly Racing Series for six divisions and several special events during the race season, which runs from May to September. Scotia Speedworld is located at Exit 6 on Highway 102, across from the Halifax Stanfield International Airport. For more information please click on ScotiaSpeedworld.ca or call our Event Hotline at (902) 873-2277 or our office at (902) 481-2514.

 

 From Joan Roue