|To: rkrw who wrote (224)||12/18/2009 12:18:33 PM|
|From: Arthur Radley|
|My guess is that they figured this would be the quickest venue to get another drug approved.......guess they didn't remember the result of Coreg and the huge market they garnered for that one. Appears that FLML and ELN are both working on this method of drug delivery......leaving me to question why I still own shares in these two. I still believe that reformulation for existing drugs will eventually be successful.....but when???? (:<)|
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|From: Arthur Radley||12/3/2014 10:51:56 AM|
|Has been a long haul on this one! Took transforming the company to get here, but hit a new high today on increasing volume. Niche market players can make money---and it appears FLML has hit on how to do it! Glad I kept a few shares in the lock-box--maybe I can now afford to buy that grandkid a Christmas gift!|
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|From: Paul Lee||12/19/2014 8:29:30 AM|
| Flamel Technologies Announces Positive Results of a Second Clinical Trial With Micropump(R) Sodium Oxybate Results Confirm Elimination of the "Middle-of-the-Night Dose" Achieved in Previous Study Meeting With FDA Will Be Requested in the First Quarter of 2015 |
LYON, FRANCE--(Marketwired - Dec 19, 2014) - Flamel Technologies (NASDAQ: FLML) today announced that its second clinical study in healthy volunteers using its proprietary Micropump® technology applied to sodium oxybate has achieved the objective of one single dose before bedtime for patients suffering from narcolepsy, confirming the results of a previous, first-in-man, study. The current dosing regimen for the standard of care, Xyrem® (sodium oxybate), in the United States is two equal, divided doses: the first dose at bedtime and the second dose 2.5 to 4 hours later. The elimination of the second dose for narcolepsy patients would not only provide more convenience, but may improve the benefit sodium oxybate provides as there will be no disruption to nighttime sleep. The potential for additional benefits, including improved safety, will be studied.
The trial was designed as a 2-arm study with 12 patients in each arm evaluating two different formulations of Micropump® sodium oxybate at a nightly dose of 4.5g, 6g and 7.5g. Each subject consumed a standard meal two hours prior to dosing. Subjects were instructed to maintain a consistent meal time and dosing schedule throughout the study. One subject dropped out of the study prior to the completion of the 7.5g dosing portion for reasons unrelated to drug. The data for both formulations at the 4.5g and 6g doses were consistent with the data seen in the previous study which showed:
The data at the 7.5g dose for both formulations were consistent with expectations given the data generated at the lower doses. While both formulations were successful, Flamel has chosen to move forward with the optimal formulation.
- Onset of action similar to Xyrem
- Cmax lower than Xyrem
- Mean blood concentration (ug/ml) at hours 7 and 8 similar to Xyrem
To date, Micropump® sodium oxybate has been tested in 40 healthy subjects across three doses among three different formulations with no safety or tolerability issues.
Flamel plans to meet with the U.S. Food and Drug Administration (FDA) before the middle of 2015. Based on current expectations, the Company plans to begin registration studies prior to the end of 2015.
Flamel's Micropump technology is protected by intellectual property through at least 2025 in the United States. Micropump is a proven drug delivery platform for the oral delivery of small molecules.
Narcolepsy is a sleep disorder involving irregular patterns in Rapid Eye Movement (REM) sleep and significant disruptions of the normal sleep/wake cycle. People with narcolepsy experience excessive daytime sleepiness, sleep attacks, cataplexy, sleep paralysis, hallucinations and disrupted nighttime sleep.
Xyrem® is sold in the United States by Jazz Pharmaceuticals plc, in Canada by Valeant Canada Limited (via license from Jazz) and in twenty-two EU countries and Mexico by UCB Pharma Limited (via license from Jazz).
About Flamel Technologies - Flamel Technologies SA's (NASDAQ: FLML) business model is to blend high-value internally developed products with its leading drug delivery capabilities. The Company markets Bloxiverz® (neostigmine methylsulfate) and Vazculep™ (phenylephrine hydrochloride) in the US and licenses the Micropump-based microparticles technology to Recipharm AB for application to the manufacturing under FDA-audited GMP guidelines of Coreg CR® (carvedilol phosphate), marketed in the USA by GlaxoSmithKline. The Company has a proprietary pipeline of niche specialty pharmaceutical products, while its drug delivery platforms are focused on the goal of developing safer, more efficacious formulations of drugs to address unmet medical needs. Its pipeline includes chemical and biological drugs formulated with its Micropump® (and its applications to the development of liquid formulations LiquiTime® and of abuse-deterrent formulations Trigger Lock™) and Medusa™ proprietary drug delivery platforms. Several Medusa-based products have been successfully tested in clinical trials. The Company is headquartered in Lyon, France and has operations in St. Louis, Missouri, USA, and Dublin, Ireland. Additional information may be found at www.flamel.com.
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|To: Arthur Radley who wrote (228)||12/19/2014 3:01:13 PM|
|From: SI Ron (Crazy Soup Man)|
|We'd like to have a logo on this board as part of our site modernization and to increase your board's visibility. We are over 600 logos on active message boards. Can you please find an appropriate image and upload it to the board? I can upload it to your board if you don't know how.|
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|From: Paul Lee||10/5/2015 11:05:13 AM|
| Flamel Ireland Limited Licenses LiquiTime(R) Technology to Perrigo for U.S. Over-the-Counter Market |
Related Quotes LYON, FRANCE--(Marketwired - Oct 5, 2015) - Flamel Technologies (NASDAQ: FLML) announced today that the Company's Irish subsidiary, Flamel Ireland Limited, has licensed exclusive U.S. rights to the LiquiTime® drug delivery platform to Perrigo's Irish subsidiary, Elan Pharma International Limited, for the U.S. Over-the-Counter (OTC) drug market. LiquiTime® is Flamel's drug delivery platform for modified, extended and controlled release of liquid oral drugs.
Flamel has entered into a multi-product agreement for extended release liquid OTC products in the U.S. market whereby Flamel will receive an upfront payment of $6.0 million and will be eligible for at least $50 million in approval and launch milestones for a minimum of seven products. In addition, Flamel will receive mid-single digit royalties on net sales. The exclusive license includes Flamel's LiquiTime® Ibuprofen and LiquiTime® Guaifenesin oral suspensions.
Flamel and Perrigo believe there is a large market opportunity for other OTC extended release liquid drug formulations, including products containing active ingredient combinations for the US cough/cold market, which analysts have estimated at $6.5 billion annually.
"We are very pleased to partner with Perrigo, one of the premier companies in the US Over-the-Counter consumer goods market. Flamel's LiquiTime® platform meets the unmet medical need for patients who are seeking the convenience of extended release liquid OTC medications. In addition, our LiquiTime® drug delivery platform is patent protected through September 2025 in the US and we will have the ability to apply for product-specific patents to extend those periods of patent protection," said Michael S. Anderson, Chief Executive Officer.
"This licensing agreement with Perrigo is another important validation of the quality and differentiation of Flamel's drug delivery platform technology. Moreover, we are pleased to accomplish one of our major commitments to investors in 2015 by putting these products into the hands of a leading OTC consumer products company that may result in an attractive set of milestone and royalty payments to our Company over time.
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|From: Paul Lee||10/22/2015 11:09:06 AM|
|The Neostigmine Shortage: A Clinical Conundrum with Few Drug Alternatives|
by Steven Greenberg, MD, FCCP; Sorin J. Brull, MD, FCARCSI (Hon); Pavan Rao, MD, MBA; Robert L. Barkin, MBA, PharmD, FCP, DAAPM, DACFM; Jeff Thiel, MS, PharmD; Joseph Szokol, MD, MBA, JD; and Richard C. Prielipp, MD, MBA, FCCM
Nationwide drug shortages affect anesthesia professionals every day.1 In 2012, a survey generated by the American Society of Anesthesiologists (ASA), and accessible on the ASA website, suggested that 97.6% of anesthesiologists experienced a drug shortage in their practices. There have been several documented reasons for drug shortages, which include raw material shortages, manufacturing quality control issues, industry consolidation, and manufacturer discontinuation. Despite governmental and provider organization support to reduce drug shortages, they appear to be on the rise.1 At the present time, no governmental agency or other entity has the accountability, authority, or responsibility to mandate a corporation or manufacturer to continue production, maintain levels of inventory and/or set prices of any drug. Drug manufacturing is a market-driven process, and pharmaceutical companies—like all corporations—must balance the needs of customers (physicians and patients), the marketplace, and shareholders. When drugs are in short supply, suspended, prohibitively expensive, or eliminated, anesthesia providers respond by searching for alternative options. However, when a drug with few alternatives becomes the focus of a drug shortage, it may significantly alter practice patterns and ultimately, patient safety.
In the previously cited ASA survey, as well as in a 2013 Survey conducted by the AANA, and accessible on the AANA website, neostigmine was one of the drugs most commonly associated with drug shortages. This shortage was in part, and interestingly, due to new U.S. Food and Drug Administration (FDA) rules. In 2011, the FDA issued revised guidance on marketed, unapproved drugs: “Compliance Policy Guide Sec 440.100, Marketed New Drugs Without Approved NDAs or ANDAs (CPG440.100).”a The FDA guidance established “an orderly approach for removing unapproved drugs from the market.” In 2013, Eclat Pharmaceuticals, the only makers of “FDA-approved” neostigmine (Bloxiverz)b sent a letter calling on the FDA to stop all 5 of its competitors (Cardinal Health, West-Ward Pharmaceuticals, Fresenius Kabi USA, American Regent and General Injectables & Vaccines) from selling the “FDA-unapproved” generic neostigmine.c In this letter to the FDA, Eclat Pharmaceuticals also claimed that the manufacturers of unapproved neostigmine “lack complete labeling and pose a potential safety hazard.” Flamel Technologies, which acquired Eclat Pharmaceuticals in 2012, significantly raised the price of Bloxiverz, the only available neostigmine preparation.d In the current marketplace in 2015, neostigmine is only manufactured by 2 companies (Fresenius Kabi and Eclat Pharmaceuticals),e which significantly increased the cost of the drug. More importantly, the shortage created a clinical conundrum for anesthesia providers because alternatives to neostigmine are quite limited. Institutions and providers across the United States may need to decide between the following choices to provide effective perioperative clinical care:
These choices, however, may be associated with substantial unintended consequences. The unexpected increase in neostigmine pricing may create considerable financial pressure on the OR pharmacy and anesthesiology budgets. Perhaps a better alternative is to minimize the waste of neostigmine by placing it in prefilled syringes, which facilitates a more cost conscious utilization of the drug. The high cost of the reversal agent may also promote more conservative use of neuromuscular blocking agents (NMBAs) in the perioperative period. However, it may also raise the danger of an increase in residual neuromuscular blockade in the PACU because providers might inadvertently under-dose patients during the reversal process in an attempt to save on the cost of neostigmine.
- Continue using neostigmine at a much higher cost
- Minimize "waste" of neostigmine by using prefilled syringes with fixed volumes/doses
- Consider an alternative like edrophonium (with premixed atropine), called “Enlon Plus”.
- Minimize or eliminate use of NMB drugs, and thus nullify the need for reversal agents altogether.
Changing to the only available alternative product, edrophonium plus atropine (“Enlon Plus” in its premixed fashion) also may have unintended consequences. Many anesthesia providers may be unfamiliar with the dosing, pharmacokinetics ,and side effects of this combination reversal alternative. For instance, there may be an increase in the incidence of central anticholinergic syndrome with the addition of atropine to edrophonium. Moreover, patients with comorbidities (specifically cardiac) may be more susceptible to the drug-induced effects of secondary tachycardia or bradycardia sometimes observed with this pre-mixed product. Additional education is certainly required to avoid drug errors and enhance clinician awareness of the potential adverse effects of this combination drug.
The difference in onset and offset of edrophonium (peak effect of 2–4 minutes) vs. neostigmine (peak effect of 6–10 minutes) must also be reviewed by anesthesia providers, and the administration should be timed appropriately. The recommended dose of Enlon Plus is 0.5–1 mg/kg edrophonium and 0.007–0.014 mg/kg atropine given intravenously over a minimum of 45–60 seconds.2 The anticholinesterase effect of edrophonium lasts approximately 70 minutes (assuming normal renal function), and therefore, it is unlikely to result in reappearance of neuromuscular block (“re-curarization”) with the intermediate acting modern muscle relaxants.2 To make it easier for clinicians, the solution is 10 mg/mL of edrophonium, and the dose range is from 0.05–0.1 mL/kg. Therefore, a 70-kg patient would typically receive 3.5–7 mL of the Enlon-Plus mixture. Lastly, the long-term availability of edrophonium is not entirely clear, particularly if the prices of “FDA-approved” neostigmine preparations start decreasing.
Edrophonium is not as effective as a reversal agent as neostigmine, because the bonds it forms to acetylcholinesterases are mostly ionic, rather than the more resistant covalent bonding of neostigmine. Thus, if edrophonium is used for reversal of neuromuscular block, the clinician should wait for sufficient spontaneous recovery (Train-Of-Four (TOF) count of 2–3) prior to reversal. Once this level of recovery is attained, the full dose of 1 mg/kg edrophonium should be administered over at least 3–5 minutes. It should be recognized that the faster the administration, the greater the peak plasma concentration of edrophonium/atropine, so the greater the potential for side effects. In patients at risk of bradycardia (elderly, pediatrics, patients on beta-blockers, etc.), the clinician should consider giving some additional atropine upfront. If TOF count is 4, and there appears to be no fade to TOF stimulation assessed subjectively, only 25%–50% of the full dose should be administered again, over at least 3–5 min.3
A final strategy to avoid the high cost of neostigmine is to refrain from using reversal agents altogether—the obvious concern with this choice is the high likelihood of residual neuromuscular blockade and its associated negative effects.4 A preferred alternative would be to monitor neuromuscular function objectively (by using an accelerograph or the integrated kinetomyograph) or at least with the use of a nerve stimulator in the TOF mode. Then, choose an appropriate reversal dose based on the degree of neuromuscular recovery.
While the dilemma of neostigmine shortage and high pricing highlights the impact of drug shortages on practice patterns, it will not be the last one. In the 2015 February issue of the APSF Newsletter, Orlovich and Kelly wrote a concise review on the drug shortage issue as it relates to anesthesia providers. They offered several factors and potential solutions to proactively prevent the ever-increasing anesthesia drug shortage epidemic.5 It is up to anesthesia organizations, business leaders, hospital administrators, and government officials to rethink viable solutions to this ever growing problem, so that our patients do not assume unnecessary perioperative risk. Lastly, but perhaps most importantly, Hsia et al. recently suggested that a clear majority of patients (60.9%) want to be informed of a drug shortage even if it made little difference to patient outcomes.6 On the other hand, informing patients of the shortages may increase their fear and anxiety unnecessarily, just prior to surgery, and therefore this disclosure needs to be reviewed carefully and critically. However, it may allow us, as providers, to stop and appreciate that our patients are becoming more concerned and knowledgeable about their care and the ever-escalating problem of drug shortages. This may be the right time to enhance our alliance with our patients and help lobby for effective changes to curb this recurring problem. Meanwhile, we must continue to prioritize patient safety and value-based care.
a. http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesbyFDA/SelectedEnforcementActionsonUnapprovedDrugs/ucm270834.htm. Accessed Aug 7, 2015.
b. http://bloxiverz.com. Accessed August 8, 2015.
Dr. Greenberg is Assistant Editor of the APSF Newsletter, Clinical Associate Professor in the Department of Anesthesiology/Critical Care at the University of Chicago Pritzker School of Medicine, and Director of Critical Care Services at Evanston Hospital, NorthShore University HealthSystems
Dr. Brull is the Patient Safety Section Editor, Anesthesia & Analgesia, Executive Committee Member of the APSF, and Professor of Anesthesiology at the Mayo Clinic, Jacksonville, FL.
Dr. Rao is an Anesthesiology Resident at the University of Chicago, Pritzker School of Medicine
Dr. Barkin is Professor of Anesthesiology, Pharmacology and Family Medicine at Rush Medical College in Chicago, IL. He is also a Clinical Pharmacologist at North Shore University Health System at Skokie and Evanston Pain Centers.
Dr. Thiel is Assistant Vice President, Pharmacy Services at NorthShore University HealthSystem.
Dr. Szokol is Vice Chairperson, Department of Anesthesiology, NorthShore University HealthSystem and Clinical Professor in the Department of Anesthesiology/Critical Care at the University of Chicago Pritzker School of Medicine
Dr. Prielipp is Chairperson of the APSF Committee on Education and Training, Executive Committee Member of the APSF, and Professor of Anesthesiology at the University of Minnesota.
Editorial Note: In a 2013 survey conducted by the AANA, 48.6% of respondents reported a neostigmine shortage as well.
- De Oliveira GS, Jr, Theilken LS, McCarthy RJ. Shortage of perioperative drugs: implications for anesthesia practice and patient safety. Anesth Analg 2011;113: 1429-35.
- Cronnelly R, Morris RB, Miller RD: Edrophonium: Duration of action and atropine requirement in humans during halothane anesthesia. Anesthesiology 1982; 57: 261-6.
- Thilen SR, Hansen BE, Ramaiah R, Kent CD, Treggiari MM, Bhanaker SM. Intraoperative neuromuscular monitoring site and residual paralysis. Anesthesiology 2012;117: 964-72.
- Murphy GS, Brull S. Residual neuromuscular block: Lessons unlearned. Part I: definitions, incidence, and adverse physiologic effects of residual neuromuscular block. Anesth Analg 2011;111: 120-8.
- Orlovich DS, Kelly RJ. Drug shortages in the US - A balanced perspective. APSF Newsletter 2015;29: 49-50.
- Hsia IKH, Dexter F, Logvinov I, et al. Survey of national drug shortage effect on anesthesia and patient safety: A patient perspective. Anesth Analg 2015;121: 502-6.
©Copyright 2015 Anesthesia Patient Safety Foundation
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