Pink Sheet is part of Informa PLC

This site is operated by a business or businesses owned by Informa PLC and all copyright resides with them. Informa PLC’s registered office is 5 Howick Place, London SW1P 1WG. Registered in England and Wales. Number 8860726.

This copy is for your personal, non-commercial use. For high-quality copies or electronic reprints for distribution to colleagues or customers, please call +44 (0) 20 3377 3183

Printed By



Executive Summary

Wyeth-Ayerst's twice-daily anti-anginal nitrate compound ISMO (isosorbide mononitrate) will be available in pharmacies in mid- March and will be "priced competitively" with other long-acting nitrate compounds, Wyeth-Ayerst said Jan. 2. ISMO was approved by FDA on Dec. 30 after a review period that began with an initial NDA filing on Dec. 28, 1983. The NDA subsequently was resubmitted on April 14, 1987. ISMO is indicated for the prevention of chronic, stable angina pectoris "due to coronary artery disease" The nitrate compound is not approved for aborting acute anginal episodes due to its slow onset of action (one hour). The clinical pharmacology section of ISMO's approved labeling states that isosorbide mononitrate is the "major active metabolite of isosorbide dinitrate...and most of the clinical activity of the dinitrate is attributable to the mononitrate." ISMO was given FDA's "1C" designation (new molecular entity with little or no therapeutic gain over existing therapies). Wyeth-Ayerst licenses ISMO from Boehringer Mannheim GmbH. Boehringer Mannheim Pharmaceuticals Corp., the German company's newly spun-out U.S. pharmaceutical arm, will copromote ISMO as one of its first U.S. commercial operations. Former Beecham President Ted Wood is joining Boehringer Mannheim's U.S. pharmaceutical business on Jan. 13 as president ("The Pink Sheet" Dec. 23, T&G- 6). ISMO is the first nitrate compound for the prevention of angina approved in 30 years, Wyeth-Ayerst said. Isosorbide dinitrate has been on the market for a number of years. The company's brand is Isordil. ICI Pharma markets an isosorbide dinitrate product under the Sorbitrate brand and more than a half- dozen generic versions also have been approved. On Dec. 26, Roberts Pharmaceuticals announced the completion of an agreement in principle with Wyeth Labs-U.K. to acquire four prescription products for sale in the U.K., including Isordil (see related T&G). The recommended dosing regimen for ISMO tablets is 20 mg (one tab) twice daily, seven hours apart. The anti-anginal effect begins one hour after dosing and reaches its peak from one-to-four hours after administration. Dosing adjustments are not necessary for elderly patients or those with "altered renal or hepatic function," labeling notes. Discussing ISMO's pharmacodynamics, labeling states that "the drug-free interval sufficient to avoid tolerance...has not been completely defined." The only dosing regimen for the twice- daily drug that did not show tolerance development was two doses given seven hours apart. "The same twice-daily regimen of ISMO tablets successfully avoided significant rebound/withdrawal effects," labeling states. ISMO was studied in placebo-controlled clinical trials lasting two to three weeks where the drug was administered in asymetric regimens (dosing intervals of seven and 17 hours) designed to avoid tolerance, labeling states. One trial tested 10 mg and 20 mg doses twice daily; another study tested 20, 40 and 60 mg doses two times a day; and three trials looked only at 20 mg doses twice daily. For at least three weeks into the trials, exercise tolerance in patients treated with ISMO 20 mg tabs "was significantly greater" than with placebo, "although there was some attentuation over time," labeling states. FDA's Dec. 30 approval letter notes that Wyeth-Ayerst, in a Dec. 27 letter to the agency, agreed to meet with FDA's Cardio- Renal Drug Products Division "to identify a study design that would enhance the current instructions for use." FDA noted that "it is understood that this study would be designed to obtain additional dose-ranging data." Labeling points out that in clinical trials, ISMO has not been "adequately" studied "in single doses less than 20 mg...while single doses greater than 20 mg have demonstrated no greater efficacy than doses of 20 mg."

You may also be interested in...

Part D Discount Liability Coming Into Focus: CMS Releases Drug Cost Data

Newly released Medicare Part D data sheds light on the sales hit that branded pharmaceutical manufacturers will face when the coverage gap discount program gets under way in 2011

FDA Skin Infections Guidance Spurs Debate On Endpoint Relevance

FDA appears headed for a showdown with clinicians and the pharmaceutical industry over the proposed new clinical trial endpoints for acute bacterial skin and skin structure infections, the guidance's approach for justifying a non-inferiority margin and proposed changes in the types of patients that should be enrolled in trials

Shire Hopes To Sow Future Deals With $50M Venture Fund

Specialty drug maker Shire has quietly begun scouting deals with a brand-new $50 million venture fund, the latest of several in-house investment arms to launch with their parent company's pipelines, not profits, as the measure of their worth




Ask The Analyst

Ask the Analyst is free for subscribers.  Submit your question and one of our analysts will be in touch.

Your question has been successfully sent to the email address below and we will get back as soon as possible. my@email.address.

All fields are required.

Please make sure all fields are completed.

Please make sure you have filled out all fields

Please make sure you have filled out all fields

Please enter a valid e-mail address

Please enter a valid Phone Number

Ask your question to our analysts