Jim, hopefully you will forgive my posting in two places. I would like to get feedback from others on KOS thread as both companies involved.
Why did Bristol Myers never do <a-once-a-day on Captopril> themselves?
Actually a good question given that Captopril (Capoten (R)) has been around a long time since it's introduction in 1977 and has very positive efficacy as an anti-hypertensive treatment.
Here's some positive comments noted in drug profiles on Captopril compared to their competing drugs, and the importance of the (ACE) family of anti-hyperintension drugs as a whole:
"In less than 15 years, angiotensin converting enzyme (ACE) inhibitors have become one of the most important classes of drugs for treating hypertension and chronic heart failure. Because of their safety, efficacy, and ability to reverse some of the structural changes associated with high blood pressure, ACE inhibitors are now recommended as first-line therapy for hypertension,
and they are the cornerstone in managing chronic heart failure. These drugs all have a similar mechanism of action: the inhibition of converting enzyme, a crucial component of the renin-angiotensin system (RAS) that is involved in the regulation of arterial blood pressure, renal hemodynamics, and fluid and electrolyte balance."
Quality of Life -- Captopril Versus Enalapril
There do not seem to be many practical differences between the various ACE inhibitors. Some are cheaper (ramipril) and some more expensive (fosinopril); some are direct acting (captopril, lisinopril) and some require prodrug activation (all others); some are given twice daily (captopril) and some once daily; and at least one has a dual renal/hepatic route of excretion (fosinopril) -- but these particular benefits have yet to translate into meaningful differences in clinical practice. They all appear safe and effective. But how do patients rank them? Testa et al. asked the patients themselves. They studied two ACE inhibitors --
captopril and enalapril -- with similar mechanisms of action, similar side effect profiles, and similar laboratory results. Subjects were 379 hypertensive male volunteers. Captopril was given 25-50 mg twice daily and enalapril 5-20 mg/day for 24 weeks, with the addition of hydrochlorothiazide if needed. The investigators used an extensive quality-of-life questionnaire
that required 30-40 minutes to complete and was sensitive enough to measure a meaningful difference.
Throughout the trial, no differences were observed in blood pressure control, frequency of withdrawal from the study, or major side effects. >>>>> However, patients receiving captopril reported more favorable changes in overall quality of life, general perceived health, health status, vitality, sleep, and emotional control. The difference was primarily in patients entering
the study with a generally good quality of life. <<<<< Both agents improved quality of life when baseline quality was low, but enalapril reduced the quality of life in the men with good quality at baseline. This difference between captopril and enalapril may be due to differences in central nervous system distribution. Recent evidence suggests that ACE inhibitors and angiotensin II antagonists reduce anxiety and improve cognitive function, possibly by cholinergic mechanisms. "The most striking finding in this study," concluded the investigators, "was that two ACE inhibitors that acted identically with regard to efficacy, adverse events, and laboratory outcomes acted quite differently with regard to quality of life." (Testa MA et
al. N Engl J Med. 1993; 328: 907-913) "
Captopril Drug Profile...from: Kwan Man Cheuk/Tsien Ka Cheong Matthew
PHA 2111/Medicinal Chemistry:
"1. The treatment of essential hypertension
Captopril is effective in the treatment of hypertension of all grades of severity.
2. Renal hypertension
Captopril is very effective in the treatment of renovascular hypertension. The initial dose should be small as severe hypertension may result.
3. Heart failure
Captopril is extremely effective in the treatment of heart failure. Special care should be taken with patients who have been treated
previously with high doses of diuretics. In addition to lowering the peripheral resistance and reducing ventricular after-load, captopril decreases right and left ventricular filling pressures and increases
cardiac output and regional blood flow."
What does this mean for FUISZ & KOS ?
Given the above favorable comments, it may be safe to say they are smart in targeting one of the well known and highly regarded generics in the industry. A once-a-day will provide a competitive edge to the other IR generics out there. Apparently, correct dosage of these anti-hypertension drugs is very important to prevent the nasty side-effects. If they improve the dosage intake with their controlled-release system this would be a major bonus, I would think.
With only two once-a-days in development, this may not be so bad. Even if Kos received a small sliver of this huge, rising < and highly competitive > market, it could still represent a sizable return. Fuisz should receive an up-front license option fee and additional license fees throughout the development period. Fuisz is also entitld to royalties bases on net sales by the partner, and fees paid are non-refundable. So to Fuisz it is just one more potential source of revenue from a string of collaborating partners.
My Question: What are the other sustained release presciption drugs in development ?
Caveat: I am a totally biased shareholder.
Dave. |
