Modafinil drug data and news

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Velcade Lung Cancer Study Begins  07 Mar 2006
...and its partner Johnson & Johnson (JNJ:NYSE - commentary - research - Cramer's Take) have started trials to examine the multiple myeloma drug Velcade as a ... - TheStreet.com

Millennium And Johnson & Johnson Reveals Phase II Study Of VELCADE ...  07 Mar 2006
...and Johnson & Johnson Pharmaceutical Research & Development LLC, revealed the initiation of a three-arm, randomized, Phase II study of VELCADE and pemetrexed ... - Trading Markets,

This week in London  07 Mar 2006
Multiple Myeloma special presentation: Presentation by Kathleen Colson, Dana Farber Cancer Institute, on recent clinical trial results for Velcade, common side ... - London Free Press,

(PRN) - 485 Courts in Session With Tyler's INCODE Municipal Court ...  07 Mar 2006
...(PRN) - Millennium and Johnson & Johnson Pharmaceutical Research & Development Initiate Randomized Phase II Trial of VELCADE(R) (Bortezomib) for Injection in ... - Bolsamania.com,

Nereus Pharmaceuticals Closes Second Tranche of $42.6 Million ...  07 Mar 2006
...generation compound could significantly enhance the market for proteasome inhibitors, which has been previously established by Millennium's Velcade(R). "With ... - PR Newswire (press release),

Velcade® plus Melphalan Shows Encouraging Activity in Multiple ...  Feb 23, 2006
According to a recent article published in the Journal of Clinical Oncology, the treatment combination consisting of Velcade® (bortezomib) and melphalan ... - Cancer Consultants (press release),

Updated Results: Velcade® Improves Survival Over Dexamethasone in ...  Feb 8, 2006
Researchers affiliated with the Assessment of Proteosome Inhibition for Extending Remissions (APEX) randomized trial of Velcade (bortezomib) versus ... - Cancer Consultants (press release),

Millennium shares slip after downgrade  Feb 28, 2006
...slid Tuesday, after an analyst saw faster than expected pressure on its Velcade cancer drug from Celgene Corp's Revlimid. JPMorgan ... - BusinessWeek

JP Morgan Cuts Millennium Pharm To Underweight >MLNM  Feb 28, 2006
JP Morgan cut Millennium Pharmaceuticals Inc. (MLNM.NAS) to underweight from neutral because of faster-than-expected pressure on the cancer drug Velcade. ... - New Ratings

Millennium shares slip after downgrade  Feb 28, 2006
NEW YORK Shares of Millennium Pharmaceuticals slid today after an analyst saw faster than expected pressure on its Velcade cancer drug from competitor ... - Eyewitness News,

Doxil® in the VAD Regimen for Myeloma Confirmed Less Toxic Than ...  Feb 28, 2006
However, recent induction regimens have incorporated newer drugs such as Thalomid® (thalidomide), Revlimid® (lenalidomide), and Velcade® (bortezomib). ... - Cancer Consultants (press release),

Need federal drug plan  Feb 22, 2006
The province's decision last week not to fund Velcade underscored this crisis for hundreds of Ontario patients and their families who have nowhere else to turn ... - Toronto Star,

Keryx Biopharmaceuticals, Inc. Commences Phase 2, Multi-Center ...  Mar 2, 2006
...of 2006, including another corporate-sponsored DFCI -led phase I/II study evaluating the safety and efficacy of KRX-0401 and bortezomib (Velcade(R)) therapy ... - PharmaLive.com (press release),

Kosan Reports 2005 Fourth Quarter and Year End Results  Mar 2, 2006
Product Development Highlights Hsp90 Inhibitor Program -- Demonstration of clinical activity of KOS-953 in combination with bortezomib (Velcade®) in patients ... - Yahoo! News (press release)

Lewis named VP of commercial law  Feb 23, 2006
Lewis played a critical role in the launch of VELCADE and has worked closely with senior leadership within the commercial organization to support the continued ... - Concord Journal,

CuraGen Stock Jumps on Upgrade Over Drug  Feb 6, 2006
...analyst Edward Tenthoff said he's interested in a move to combine PXD101 with Cambridge, Mass.-based Millennium Pharmaceuticals Inc.'s drug Velcade, which is ... - Forbes

US Stocks Fall on Consumer Confidence Report; Google Plunges  Feb 28, 2006
The drug developer may miss its 2006 sales forecast as its Velcade cancer drug loses market share more rapidly than expected to Celgene Corp.'s Revlimid, said ... - Bloomberg

Schaeffer's Daily Bulletin for 2/28/2006  Feb 28, 2006
JP Morgan downgraded Millennium Pharmaceuticals (MLNM) to "underweight" from "neutral," citing pressure on the cancer drug Velcade ... ... - Schaeffers Research,

Millennium Announces New Senior Vice President of Human Resources  Feb 9, 2006
About Millennium Millennium Pharmaceuticals, Inc., a leading biopharmaceutical company based in Cambridge, Mass., markets VELCADE(R) (bortezomib) for Injection ... - PR Newswire (press release),

Biotech's Mid Caps Post Solid Gain in February  Mar 1, 2006
...weakened to close at $10.48, up 1% for the month, after an analyst saw faster than expected pressure on its Velcade cancer drug from Celgene Corp's Revlimid. ... - PR Newswire (press release),

Lehman Brothers Ninth Annual Global Healthcare Conference to ...  Mar 2, 2006
Millennium Pharmaceuticals, Inc., a leading biopharmaceutical company based in Cambridge, Mass., markets VELCADE(R) (bortezomib) for Injection, a novel cancer ... - PharmaLive.com (press release),

Drug stocks slide as King plunges  Feb 28, 2006
...to $10.35. Analysts at JP Morgan downgraded the stock to underweight, citing concerns over flattening sales of its drug Velcade. - Investor's Business Daily (subscription)

CuraGen upgraded to "outperform"  Feb 7, 2006
...mention that histone deacetylease (HDAC) inhibitor PXD101 is expected to be most effective in combination therapy with Millennium's Velcade, which would have ... - New Ratings

Cytogen Reports Fourth Quarter and Full Year 2005 Financial ...  Feb 23, 2006
...preclinical studies involving the use of QUADRAMET both as a monotherapy and in combination with the proteasome inhibitor bortezomib (Velcade(R), Millennium ... - MSN Money

Biotech Investing for the Long Haul  Feb 22, 2006
Since the company is trying to expand its business outside of key drug Velcade and should be investing appropriately, the desire to turn profitable appears to ... - Morningstar.com,

Myeloma group to host talk at Thursday luncheon  Feb 20, 2006
Lucie Counties. "There also will be a short update on Velcade, an oncology drug, from the American Society of Hematology Meeting. - Palm Beach Daily News,

Millennium Announces Pharmaceutical Industry Leader Joins the ...  Feb 6, 2006
Millennium Pharmaceuticals, Inc., a leading biopharmaceutical Company based in Cambridge, Mass., markets VELCADE(R) (bortezomib) for Injection, a novel cancer ... - PR Newswire (press release),

Cancer Patients Do Not Get Uniform Treatment  Jan 31, 2006
For instance, cancer drug Velcade is not available to patients in Ontario, as the entire treatment with the drug costs as much as $60 thousand. ... - MedIndia,

CuraGen Reports Fourth Quarter and Year End 2005 Financial Results ...  Feb 2, 2006
...role in the treatment of multiple myeloma, ovarian and colorectal cancers, and more recently, in a myeloma study of PXD101 in combination with Velcade(R) and ... - MSN Money

Drugs for cancer easy to get in BC  Feb 1, 2006
In Ontario, for example, Velcade does not have full, approved funding to treat a relapse of multiple myeloma, nor does Tarceva for non-small-cell lung cancer ... - Globe and Mail,

CNS Active Drugs

Methylphenidate - In a single-dose study in healthy volunteers, coadministration of modafinil (200 mg) with methylphenidate (40 mg) did not cause any significant alterations in the pharmacokinetics of either drug. However, the absorption of PROVIGIL may be delayed by approximately one hour when coadministered with methylphenidate.

Dextroamphetamine - In a single dose study in healthy volunteers, simultaneous administration of modafinil (200 mg) with dextroamphetamine (10 mg) did not cause any significant alterations in the pharmacokinetics of either drug. However, the absorption of PROVIGIL may be delayed by approximately one hour when coadministered with dextroamphetamine.

Clomipramine - The coadministration of a single dose of clomipramine (50 mg) on the first of three days of treatment with modafinil (200 mg/day) in healthy volunteers did not show an effect on the pharmacokinetics of either drug. However, one incident of increased levels of clomipramine and its active metabolite desmethylclomipramine has been reported in a patient with narcolepsy during treatment with modafinil.

Triazolam - In the drug interaction study between PROVIGIL and ethinyl estradiol (EE₂), on the same days as those for the plasma sampling for EE₂ pharmacokinetics, a single dose of triazolam (0.125 mg) was also administered. Mean C_max and AUC^0-∞ of triazolam were decreased by 42% and 59%, respectively, and its elimination half-life was decreased by approximately an hour after the modafinil treatment.

Monoamine Oxidase (MAO) Inhibitors - Interaction studies with monoamine oxidase inhibitors have not been performed. Therefore, caution should be used when concomitantly administering MAO inhibitors and modafinil.

Other Drugs

Warfarin - There were no significant changes in the pharmacokinetic profiles of R- and S- warfarin in healthy subjects given a single dose of racemic warfarin (5 mg) following chronic administration of modafinil (200 mg/day for 7 days) followed by 400 mg/day for 27 days) relative to the profiles in subjects given placebo. However, more frequent monitoring of prothrombin times/INR is advisable whenever PROVIGIL is coadministered with warfarin.

Ethinyl Estradiol - Administration of modafinil to female volunteers once daily at 200 mg/day for 7 days followed by 400 mg/day for 21 days resulted in a mean 11% decrease in C_max and 18% decrease in AUC_0-24 of ethinyl estradiol (EE₂; 0.035 mg; administered orally with norgestimate). There was no apparent change in the elimination rate of ethinyl estradiol.

Cyclosporine - One case of an interaction between modafinil and cyclosporine, a substrate of CYP3A4, has been reported in a 41 year old woman who had undergone an organ transplant. After one month of administration of 200 mg/day of modafinil, cyclosporine blood levels were decreased by 50%. The interaction was postulated to be due to the increased metabolism of cyclosporine, since no other factor expected to affect the disposition of the drug had changed. Dosage adjustment for cyclosporine may be needed.

Potential Interactions with Drugs That Inhibit , Induce, or are Metabolized by Cytochrome P-450 Isoenzymes and Other Hepatic Enzymes

In in vitro studies using primary human hepatocyte cultures, modafinil was shown to slightly induce CYP1A2, CYP2B6 and CYP3A4 in a concentration-dependent manner. Although induction results based on in vitro experiments are not necessarily predictive of response in vivo, caution needs to be exercised when PROVIGIL is coadministered with drugs that depend on these three enzymes for their clearance. Specifically, lower blood levels of such drugs could result.

The exposure of human hepatocytes to modafinil in vitro produced an apparent concentration-related suppression of expression of CYP2C9 activity suggesting that there is a potential for a metabolic interaction between modafinil and the substrates of this enzyme (e.g., S-warfarin and phenytoin). In a subsequent clinical study in healthy volunteers, chronic modafinil treatment did not show a significant effect on the single-dose pharmacokinetics of warfarin when compared to placebo.

In vitro studies using human liver microsomes showed that modafinil reversibly inhibited CYP2C19 at pharmacologically relevant concentrations of modafinil. CYP2C19 is also reversibly inhibited, with similar potency, by a circulating metabolite, modafinil sulfone. Although the maximum plasma concentrations of modafinil sulfone are much lower than those of parent modafinil, the combined effect of both compounds could produce sustained partial inhibition of the enzyme. Drugs that are largely eliminated via CYP2C19 metabolism, such as diazepam, propranolol, phenytoin (also via CYP2C9) or S-mephenytoin may have prolonged elimination upon coadministration with PROVIGIL and may require dosage reduction and monitoring for toxicity.

Tricyclic antidepressants - CYP2C19 also provides an ancillary pathway for the metabolism of certain tricyclic antidepressants (e.g., clomipramine and desipramine) that are primarily metabolized by CYP2D6. In tricyclic-treated patients deficient in CYP2D6 (i.e., those who are poor metabolizers of debrisoquine; 7-10% of the Caucasian population; similar or lower in other populations), the amount of metabolism by CYP2C19 may be substantially increased. PROVIGIL may cause elevation of the levels of the tricyclics in this subset of patients. Physicians should be aware that a reduction in the dose of tricyclic agents might be needed in these patients.

In addition, due to the partial involvement of CYP3A4 in the metabolic elimination of modafinil, coadministration of potent inducers of CYP3A4 (e.g., carbamazepine, phenobarbital, rifampin) or inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole) could alter the plasma levels of modafinil.