March 5, 2007
March 28, 2007
Antihypertensive agent (direct renin inhibitor)
Treatment of hypertension, as monotherapy or combined withother antihypertensive agents.
Aliskiren 150mg, 300mg; tabs.
Integrated Communications (professional)
Euro RSCG Life x2 (medical education)
Novartis wasfirst to the USmarket with an oral renin inhibitor, Tekturna. Known as Rasilez abroad, thedrug also has been approved in the EU and in Switzerland. Analysts haveestimated peak sales of between $2.5 billion to $3.5 billion for the pill,which research shows lowers blood pressure better than other commonly-used BPmedicines, like ACE inhibitors and certain diuretics. Evidence suggests it’s alsouseful in combination, although not necessarily with Novartis’ own leading angiotensinreceptor blocker Diovan—something that could hamper sales. Another unknown is how the Swiss firm’s recentdecision to lay off some 1,260 sales and marketing posts will impact Tekturna’srollout.
|Antihypertensives US sales ($000s) last 5 years|
|Source: IMS Health, Oct. 2007
|Top 5 antihypertensives|
|Jan.-June ’07 US sales ($000s)||% sales growth over Jan.-June ‘06|
|Source: IMS Health, Oct. 2007
Tekturna is a new class of anti-hypertensive, offeringdirect renin inhibition. As a new class, both specialists and PCPs areextremely interested in trying it, hoping for better efficacy and tolerabilityfor their patients, not only as monotherapy but in combination with currentanti-hypertensives as well. Current anti-hypertensive classes have theadvantages of familiarity and long-term data in treating a variety ofcardiovascular co-morbidities and reducing cardiovascular risk. Tekturnamay enjoy a lively uptake as physician “give it a try,” but it may not become amajor force until this long-term data becomes available.
—Edwin Rupert, senior consultant, GfK V2, October 2007
Also in the Pipeline(according to Adis R&D Insight)
No competitor compounds in phase III or pre-registration, US
NovartisBP drug sees approval in Europe
Productnews from the 03/06/07 news brief
Novartisasks FDA for Galvus review extension
FDAdelays approval of Novartis’ Galvus
Novartisgets FDA nod for blood-pressure pill
Force in the Field
TheTop 50: Integrated Communications
The Top 60: ICC
Studyshows Galvus less effective than generic: Novartis
Aliskiren is an orally active, nonpeptide, potent directrenin inhibitor that decreases plasma renin activity (PRA) and inhibits theconversion of angioten-sinogen to angiotensin I. Unlike ACE inhibitors andangiotensin receptor blockers, whose effects suppress the negative feed-backloop leading to a compensatory rise in plasma renin concentration, aliskirenblocks the effect of increased renin levels so that PRA, angiotensin I andangiotensin II are reduced.
Aliskiren may be administered with other antihypertensive agents,however it is not known whether additive effects are present when aliskiren isused with ACE inhibitors or beta blockers.
The efficacy of aliskiren was evaluated in six randomized, double-blind,placebo-controlled 8-week trials involving patients with mild-to-moderatehypertension. Approximately 2,730 patients were given doses of 75–600mg of aliskirenand 1,231 patients were given placebo. Patients taking aliskiren showedreasonable blood pressure lowering effect at 150–300mg with no further increasein effect at 600mg. A substantial portion of effect was observed within 2 weeksof treat-ment. Patients in these trials continued open-label aliskiren for upto one year. A persistent BP lowering effect was seen by a randomizedwithdrawal study (patients randomized to continue drug or placebo), whichshowed a statistically significant difference between patients kept onaliskiren and those given placebo.
Aliskiren was also evaluated in combination with otherantihypertensives. In these studies, BP reductions when used in combinationwith hydrochlorothiazide or valsartan were greater than the reductions seenwith either aliskiren, HCTZ, or valsartan monotherapy. Aliskiren 150mg, whenadministered with amlodipine 5mg provided additional BP reduction, however thecombination was not statistically significantly better than amlodipine 10mg.Aliskiren has not been studied in combination with maximal doses of ACEinhibitors.
Diarrhea, hypotension, cough, rash, edema, elevated uricacid, gout, renal stones; rare: angioedema.
=18yrs: initially 150mg once daily, may increase to 300mg oncedaily if BP not adequately controlled. May be given with otherantihypertensives (see literature).
< 18yrs: not recommended
Moderate to severe renal dysfunction. History of dialysis.Nephrotic syndrome. Renovascular hypertension. Correct salt/volume depletionbefore starting therapy or start under close supervision. Monitor forhyperkalemia in diabetics. Pregnancy (Cat.C in 1st trimester; Cat.D 2nd and 3rdtrimesters); discontinue as soon as pregnancy detected. Nursing mothers: notrecommended.
Decreases furosemide plasma levels; may have diminishedeffect. Potentiated by atorvastatin, ketoconazole. Antagonized by irbesartan.Caution with max doses of ACE inhibitors.