Simcor

Product
Simcor

Approval Date
February 15, 2008

Release Date
March 2008

Companies
Abbott Laboratories

Class
HMG-Co-A reductase inhibitor and extended-release niacin,nicotinic acid.

Indication
To reduce LDL cholesterol and triglycerides, or to increaseHDL cholesterol, in patients with primary hypercholesterolemia and mixeddyslipidemia when treatment with simvastatin monotherapy or niacinextended-release monotherapy is considered inadequate.

Active Ingredient
Niacin extended-release 500, 750, or 1000mg/simvastatin 20mg;tabs.

Agency Roster
Compass Healthcare Communications (Consumer)

MarketingStrategy/Execution
In the race to combine niacin with a generic version ofMerck’s off-patent statin simvastatin, Abbott appears to have pole position.Its new combo drug, Simcor, pairs simvastatin with the extended-release form ofniacin found in Niaspan. The company is trying to make the most of first-moveradvantage. The drug is set to launch in March, and Belgian firm Solvay willprovide sales support in the USthanks to a co-promotion deal inked late last year. Simcor is approved for usealong with diet to lower patients’ LDL cholesterol and triglyceride levelswhile raising HDL. Analysts say Simcor could add $500 million in peak sales by2011 or 2012, putting Simcor in the same league as Niaspan, which generated$658 million in 2007 sales. The new product is likely to erode sales ofAdvicor, which joins Niaspan with lovastatin, a lower-strength statin. It couldalso face competition from Merck’s Cordaptive, another fixed-dose cholesterolcombo product that could see approval later this year.

Physician Outlook
Simcor—marketed by Abbott—is the first fixed-dosecombination of two widely prescribed cholesterol therapies, Niaspan (Abbott’sproprietary niacin extended-release) and simvastatin. It’s approved as asecond-line therapy—after Niaspan or simvastatin monotherapy is inadequate—for lowering LDL and raisingHDL in patients with mixed dyslipidemia. According to the physicians respondingto GfK Market Measures 2007 research on anti-dyslipidemic agents, almosttwo-thirds of Niaspan’s prescribing occurs along with a statin, which bodeswell for Simcor’s chances of success. The known “flushing” side effect ofNiaspan has been a reason for discontinuance in the past, and our 2008 researchwill measure whether the impact of this side effect continues in this fixeddose combination.

At the end of Q2, a PDUFA date is scheduled for Merck’s newCordaptive, a “low-flush” niacin; so it will be interesting to see if physicians(and patients) needing the HDL elevation that niacin can offer will flock tothis form rather than the fixed dose combination which will hit the marketfirst.

—Anna Marie Napolitano, VP, category business leader, cardiology,GfK Market Measures

Also in the Pipeline(according to Adis R&D Insight)
Drug: AEGR 733
Manufacturer: Bristol-Myers Squibb
Indication: Hypercholesterolaemia
Active Ingredient: AEGR 733
Phase: III

Drug: Pravafen
Manufacturer: Galephar Pharmaceutical Research
Indication: Hyperlipidaemia
Active Ingredient: Fenofibrate/pravastatin
Phase: III

Drug: Lapaquistat
Manufacturer: Takeda
Indication: Hyperlipidaemia
Active Ingredient: Lapaquistat acetate
Phase: III

Drug: Cordaptive
Manufacturer: Merck & Co.
Indication: Hyperlipidaemia
Active Ingredient: Niacin, laropiprant, simvastatin
Phase: III

Drug: Rosuvastatin
Manufacturer: Abbott Laboratories
Indication: Hyperlipidaemia
Active Ingredient: Choline fenofibrate
Phase: III

Drug: Livalo
Manufacturer: Nissan Chemical Industries
Indication: Hyperlipidaemia
Active Ingredient: Pitavastatin
Phase: III
Source: Wolters Kluwer Health

Recent MM&MCoverage
FDAapproves Abbott’s Simcor cholesterol combo drug
AbsorbingKos, Abbott slashes sales force
ProductNews

Pharmacology
Simcor combines the HMG-CoA reductase inhibitor, simvastatin, and thenicotinic acid derivative, extended-release niacin (Niaspan, also fromAbbott).

Clinical Trials
Simcor was compared to simvastatin 20mg and 80mg in 641 patientswith type II hyperlipidemia or mixed dyslipidemia in a 24-week study.Group A included those with elevated non-HDL levels who had been takingsimvastatin 20mg; these patients were randomized to either Simcor1000/20, Simcor 2000/20, or simvastatin 20mg. The non-HDL-C loweringwith Simcor 2000/20 and 1000/20 was significantly greater than thatachieved with simvastatin 20mg.

Group B enrolled patients who had been takingsimvastatin 40mg and had elevated non-HDL levels; these patients wererandomized to either Simcor 1000/40, Simcor 2000/40, or simvastatin80mg. The non-HDL-C lowering with Simcor 2000/40 and Simcor 1000/40 wasnon-inferior to that achieved with simvastatin 80mg.

Simcorwas not superior to simvastatin in lowering LDL-C in either group. Inboth groups, Simcor was superior to simvastatin in lowering TG andraising HDL.

Adverse Reactions
Flushing, headache, pruritus, GI upset, back pain; elevated ALT/AST, myopathy, rhabdomyolysis with renal failure.

Adults
Take once daily at bedtime with low-fat snack. Swallow whole. Naive toor switching from immediate-release niacin: initially one 500/20 tab.May increase at 4-wk intervals by up to 500mg/day (ext-rel niacincomponent); maintenance: 1000/20 to 2000/40 once daily. May substitutefor previously-titrated ext-rel niacin at equivalent doses. Retitrateif therapy interrupted ≥7 days. To reduce flushing, pretreat withaspirin or an NSAID.

Children
Not recommended.

Contraindications
Active liver or peptic ulcer disease. Unexplained persistent elevatedtransaminases. Arterial bleeding. Pregnancy (Cat.X). Nursing mothers.

Precautions
Do not substitute for equivalent doses of immediate-release niacin.Substantial alcohol consumption. History of liver disease. Monitortransaminases (at baseline, every 12wks for 1st 6 mos, thenperiodically); discontinue if levels ≥3xULN persist or ifsigns/symptoms of liver disease occur. Discontinue if myopathy isdiagnosed or suspected. Suspend therapy before surgery and if majormedical event occurs. Renal dysfunction. Gout. Monitor blood glucose,PT, platelets.

Interactions
Avoid other niacin, potent CYP3A4 inhibitors (eg, azole antifungals,macrolides, HIV PIs, nefazodone, grapefruit juice >1qt/day),gemfibrozil, fenofibrate, cyclosporine, danazol. Potentiated byamiodarone and verapamil (limit simvastatin to 20mg/day). Separatedosing of bile acid sequestrants by 4?6hrs. Postural hypotension withganglionic blockers, vasoactive drugs. Monitor warfarin, digoxin,antidiabetics.