Biotech Values

[poorgradstudent]

Speedel:

I have a couple of spies at this meeting, so hopefully I can get some of the specific numbers in due time.

However, some of these data are a rehash, and not well presented. For example:

>3. (Bad) Adding to a diuretic did not materially improve results.<

Actually, despite how the PR words it, the combination is better than both as monotherapy (see abstract #1 from American Society of Hypertension below).

>4. (Bad) Rasilez is apparently not synergistic with Norvasc (the leading calcium-channel blocker) and the clinical benefit may not even be additive.<

? They announced that BP reduction of the combo was better than that over 5 mg amlodipine / norvasc alone. Are you drawing a distinction between synergy and additive, or am i missing something?

>5. (Bad) Rasilez is apparently not synergistic with Diovan (the leading angiotensin-receptor blocker or “ARB”) and the benefit may not even be additive.<

True. And yet, they now report testing with ramipril (ACE inhibitor) and reported additional, stat sig reduction in BP for the combo over monotherapy. There is controversy as to which are better, ace-i or arb, so perhaps this discrepancy in the spp100 combo trial outcomes is a window into the differences for ace-i vs. arb.

Two points:

- I've not dug through the data extensively, so i may be missing some of the nuances of their monotherapy versus combo therapy comparisons. I sold Speedel so I've not been following as closely.

- The additional change in BP for a combo over a monotherapy need not be very large in order to see a downstream difference. In the HOPE study, they noted a 20% reduction in MI risk with a 3 and 1 mm Hg reduction in systolic and diastolic BP, respectively. Real data will obviously be interesting, but i would speculate that future data will show that an additional decrease in BP (rather than a larger "synergistic" decrease) for a combo therapy would still have a tangible benefit over the monotherapy.

- For those interested / curious, there is an ongoing trial, ONTARGET, that is testing ARB and ACE-I alone or in combination. Scientifically, one would probably not expect a large decrease in BP for the combo versus either monotherapy alone (targeting same pathway), but a small additional decrease in BP may have a larger impact on the risk of a cardiac event. We'll see.

====

Abstract #1:

[P-228] The Novel Oral Renin Inhibitor Aliskiren Provides Effective Blood Pressure Control in Patients with Hypertension When Used Alone or in Combination with Hydrochlorothiazide

A. Villamil, S. Chrysant, D. Calhoun, B. Schober, H. Hsu, J. Zhang Fundapres, Las-Heras 2910-Piso 1A, Buenos Aires, Argentina; Oklahoma Cardiovascular and Hypertension Center University of Oklahoma, Oklahoma City; Vascular Biology and Hypertension Program, University of Alabama at Birmingham; Novartis Pharmaceuticals Corporation, East Hanover, NJ

Aliskiren is the first orally active renin inhibitor, a new antihypertensive class in development. This study evaluated the antihypertensive efficacy and safety of aliskiren, alone or in combination with the diuretic hydrochlorothiazide (HCTZ), in hypertensive patients.
Following a 24 week single-blind placebo run-in, 2776 patients aged 18 years with the criterion of mean sitting diastolic blood pressure (MSDBP) 95109mmHg were randomized to receive 8 weeks double-blind treatment with aliskiren (75, 150 or 300mg), HCTZ (6.25, 12.5 or 25mg), aliskiren and HCTZ (A/H), or placebo in a factorial design.
Aliskiren monotherapy was superior to placebo in reducing MSDBP; mean reductions were 8.7, 8.9, and 10.3mmHg at doses of 75, 150 and 300mg, respectively, vs 6.9mmHg with placebo (p=0.0002 overall with Dunnetts multiple comparisons procedure). Aliskiren monotherapy significantly reduced mean sitting systolic blood pressure (MSSBP), by 9.4, 12.2 and 15.7mmHg, vs 7.5mmHg with placebo (p<0.0001 overall by Dunnetts procedure). Combination treatment was superior to each component monotherapy; both aliskiren and HCTZ had statistically significant contributions to the combined BP-lowering effect (p<0.0001 for the overall test for both MSDBP and MSSBP). The greatest mean reduction, of 21.2/14.3mmHg, was seen with A/H 300/25mg. Responder rates (patients with MSDBP <90mmHg and/or 10mmHg decrease) were significantly higher with aliskiren 300mg (64%) and all combinations (5881%) than placebo (46%; all p<0.05). Combinations of A/H 75/25, 150/25, 300/12.5 and 300/25mg had significantly greater responder rates than each component monotherapy (all p<0.05). Active treatments were well-tolerated; overall incidences of adverse events (AEs) were similar in placebo and all mono/combination therapy groups, with low rates of discontinuation due to AEs (04.4%).
This study demonstrated that aliskiren is an effective antihypertensive when given as monotherapy, and provides significant additional BP reductions when combined with HCTZ treatment.