l F-~C REPORTS(cid:173)
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`PRESCRIPTION PHARMACEUTICALS AND BIOTECHNOLOGY
`
`F-0-C Reports introduces ...
`
`"The Pink Sheet"
`I
`
`You like it \IIJeekly. You'll love it daily.
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`Up-to-date pharma/biotcch news- at
`rrom ,your trusted source for
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`
`THE NEWS THIS WEEK
`
`Vol. 66, No. 7
`
`February 16, 2004
`
`Erbitux Clears FDA; last Big Approval Of McClellan Era?
`• BRISTOL/IMCLONE EXPECT SECOND fRB/TUXMANUFACTURING SITE APPROVAL in July. Colorectal cancer treatment will
`be launched with product from Lonza Biologics facility. Approval is first step in Bristol's turnaround strategy ...................... 3
`
`fRB/TUXSURVIVAL STUDY TO BE SUBMITTED TO FDA BY EARLY 2007, IMCLONE SAYS following accelerated approval
`•
`Feb. 12. Two 1,500-patient studies are expected to complete enrollment in second quarter 2005 and fourth quarter 2006.
`Erbitux review did not require advisory cmmnittee opinion, FDA says, because "the data stood on its own merits" ................ 4
`
`FDA COMMISSIONER McCLELLAN MAY BE MOVING AGENCIES; CMS SPECULATION indicates importance of Medicare Rx
`•
`to Bu'sh Administration. McClellan's background is perfect for CMS, though FDA post is viewed as more attractive .......... 27
`
`• U.S. annual drug spend will reach $520 bil. in 2013, CMS projects, close to triple the expenditure in 2003 ...................... 29
`
`• Pfizer relies on "healthy competition" among research teams to preserve entrepreneurial spirit of discovery
`scientists. Company recognizes "dark side" to scale, tries to preserve spirit of loyalty to "the project." Pfizer does
`not plan sales force cuts, despite what it sees as "invitation" to do so from competitors ................................................... 13
`
`• GSK not interested in making "White Knight" bid for Aventis; company remains confident that internal R&D efforts
`will generate future growth. GSK faces "transition" year in 2004 ....................................................................................... 7
`
`• Aventis/Genta oncologic Genasense is expected to receive advisory committee review in early May ................................... 6
`
`• Hormone therapy "black box" class warning on dementia risk requested by Fr
`Prempro/Premarin already includes a dementia warning, but not a "black box" ....... .
`
`~beling for Wyeth's
`............................... 19
`
`• Wyeth Prevnarallocation plan extended to July; providers will receive 80% of av,f'"
`
`•
`
`"Shared exclusivity" could apply to eight first-time generics over next two years, FL
`
`,. ..,. ...................... 20
`
`..................... 23
`
`• Dr. Reddy's AmVaz approval stayed; FDA re-evaluating source of data supporting competit-. ··
`
`.:; Norvasc ........... 24
`
`• PhRMA close to deal with Rep. Tauzin; communications, reg affairs changes reflect scope of tra11.,1tion process .............. 25
`
`• Merck will give drugs free to Medicare "debit" card qualifiers after their $600 transitional assistance grant is used up.
`Merck/Schering-Plough's Zetia in not included in the offer .............................................................................................. 33
`
`• Medco's cash reserves will give the company flexibility in its approach to the Medicare Rx benefit, firm says ................... 33
`
`• Rx supply chain should be on "code red" for possible counterfeits ahead of April 1 implementation date for paper
`pedigrees, specialty distributor maintains. Dubious products may flood market before pedigree requirement kicks in .... 36
`
`Contents copyrighted © F-D-C Reports, Inc. 2004; protected by U.S. Copyright Law. Reproduction, photocopying, storage or transmission by magnetic or electronic means strictly
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`301-657-9830.
`
`

`
`"The Pink Sheet,'
`
`17
`
`PPD will adopt Merck/Schering-Plough's Zelia model
`in developing Bayer's implitapide as an add-on therapy
`in the lipid-lowering market, PPD subsidiary MRL
`International CEO Evan Stein, MD/PhD, said.
`
`"We're not looking to compete with the statin market."
`While "no new agent is going to replace statin
`therapy ... we've seen ezetimibe, Zetia, come onto the
`market and obtain a significant market share," Stein
`said during PPD's investor day Feb. 5.
`
`Zetia is similarly targeted. By contrast, Merck expects
`the Zetia/Zocor fixed-dose combination pending at
`FDA to compete directly with single-agent statins for
`patients who are diagnosed with high cholesterol but
`not treated ("The Pink Sheet" Dec. 22, 2003, p. 23).
`
`PPD suggested implitapide could eventually be used as
`a triple combination therapy with Zetia and a statin. In
`that case, Stein estimated that LDL-cholesterol
`reductions could range between 66%-72%.
`
`PPD is conducting Phase II proof-of(cid:173)
`concept studies on the use of implitapide
`(BA Y-13-9952) as an add-on to statin
`therapy. The contract research organization
`licensed the microsomal triglyceride
`transfer protein inhibitor from Bayer.
`
`PPD expects Bayer will be interested in
`buying back rights to implitapide after
`seeing the Phase II results. "If they meet, I
`think, even a reasonable hurdle, Bayer will
`be pretty keen to take it," Stein
`maintained.
`
`Implitapide could
`mark Bayer'sreturn to
`the lipid-lowering
`market after the 2001
`Baycol withdrawalo
`Bayer will have the opportunity to relicense
`PPD is hoping to demonstrate implitapide's safety and
`implitapide from PPD by reimbursing Phase II costs
`efficacy in homozygous and severe heterozygous
`and establishing milestone and royalty payments.
`familial hypercholesterolemia "where even high-dose
`statins are ineffective or inadequate," Stein said. The
`drug is also being studied for hypertriglyceridemia.
`
`The studies, which will enroll approximately 200
`patients, are expected to position the drug as a way to
`improve upon statin therapy, much in the same way
`that Zetia is marketed, Stein said.
`
`"The addition here of another 18% to 24% [LDL
`reduction] would allow us to build on current therapy,"
`he said. Zetia's success "provides an equal opportunity
`for other drugs that can produce 18% to 24% LDL
`reduction safely in a single-dose pill on top of all
`existing therapy."
`
`When used as an add-on to a statin, Zetia has a
`statistically significant effect on reducing LDL
`cholesterol. For example, across all Lipitor
`(atorvastatin) doses the combination reduces LDL
`levels 56% versus 44% with the statin alone.
`
`Some analysts have questioned the pace of Zetia' s
`uptake, however; new and total prescription share in
`December was 5.2% and 4.9%, after a little over a year
`on the market ("The Pink Sheet" Feb. 2, 2004, p. 11).
`
`Patients initially targeted for implitapide therapy will
`likely be the 5%-7% of high cholesterol patients that
`are statin-intolerant and the 10% -15% who are at high
`risk for cardiovascular disease and have not reached
`their LDL goals, Stein indicated.
`
`"One of the things that may drive them is if they don't
`take it, they know a number of other major pharma
`would probably. They are speaking to us and are
`interested in the results," Stein said.
`
`Implitapide would mark Bayer's return to the lipid(cid:173)
`lowering market; the company withdrew the statin
`Baycol (cerivastatin) in 2001 due to reports of
`rhabdomyolysis, including deaths ("The Pink Sheet"
`Aug. 13, 2001, p. 4).
`
`While Stein acknowledged that MTP inhibitor projects
`have been pursued by a number of companies, ·
`including Bristol-Myers Squibb, Johnson & Johnson
`and Pfizer, he argued that the toxicity seen with some
`of those projects was related to the high doses used
`during trials
`
`"None of them were looking at LDL reductions or
`cholesterol reductions" as low as the 20% range, he
`said. "They didn't consider that viable in terms of
`marketing. There was no Zetia on the market, so there
`was no model for them."
`
`PPD is conducting three 39-week Phase II studies with
`dose titration occurring every five weeks based on safety
`and tolerability examined at four weeks. The starting
`dose will be 10 mg daily, escalating by 5 mg/day every
`five weeks to a maximum 40 mg/day. + +
`
`Unauthorized photocopying is prohibited by law. See page one.