GLG News by Kuldeepak Sharma, PhD

Implications: As a pharmaceutical consultant working in pain management area, I think lower dose will offer similar efficacy as Soma 350 mg but with a more favorable tolerability profile. Last week, Last week, The Food and Drug Administration (FDA) have approved 250 mg (lower dose) of Soma (carisoprodol) for treatment of painful musculoskeletal conditions such as backache. As a pharmaceutical consultant working in pain management area, I think lower dose will offer similar efficacy as Soma 350 mg but with a more favorable tolerability profile. FDA approved lower dose based on two randomized, double-blind, placebo-controlled, multi-site parallel group studies which have been ongoing for several years and included more than 1,300 patients. I think Soma is a well-established brand and generates around 10 million prescriptions per year. Soma 250mg is granted a minimum 3 year exclusivity period in the US.

Analysis: As a pharmaceutical consultant working in pain management area, I think lower dose will offer similar efficacy as Soma 350 mg but with a more favorable tolerability profile.

Last week, The Food and Drug Administration (FDA) have approved 250 mg (lower dose) of Soma (carisoprodol) for treatment of painful musculoskeletal conditions such as backache. Carisoprodol is a centrally acting skeletal muscle relaxant that does not directly relax tense skeletal muscles in man. The mode of action of carisoprodol in relieving acute muscle spasm of local origin has not been clearly identified, but may be related to its sedative properties. FDA approved lower dose based on two randomized, double-blind, placebo-controlled, multi-site parallel group studies which have been ongoing for several years and included more than 1,300 patients. I think Soma is a well-established brand in the US and the substance carisoprodol generates around 10 million prescriptions per year. Average daily cost of Soma is about $7 daily based on online information. Soma 250 mg is now the only available low-dose treatment of carisoprodol that can offer similar efficacy as Soma 350 mg but with a more favourable tolerability profile. Soma 250mg is granted a minimum 3 year exclusivity period in the US. The launch will start immediately.

Implications:  Food and Drug Administration (FDA) has approved the first generic versions of Coreg (carvedilol).  It is good news for patients. Coreg is a widely used medication that is FDA-approved to treat high blood pressure, mild to severe chronic heart failure and left ventricular dysfunction following a heart attack. Generic Coreg contains same active ingredients (Carvedilol) as brand-name drugs and work the same way.  Carvedilol tablets in four strengths (3.125 milligrams, 6.25 mg, 12.5 mg and 25 mg) are manufactured by about 15 generic drug companies. All 15 pharmaceutical companies got approval on September 5, 2007. The labeling of the generic products may differ from that of Coreg because parts of the Coreg labeling are protected by patents and/or exclusivity. Total annual market sales for Carvedilol Tablets were $1.6 billion . Overall I think it is a cost effective and safe alternative to expensive brand name drug product for patients.

Analysis:

Food and Drug Administration (FDA) has approved the first generic versions of Coreg (carvedilol).  It is good news for patients. Carvedilol is indicated for the treatment of mild-to-severe heart failure of ischemic or cardiomyopathic origin, usually in addition to diuretics, ACE inhibitor and digitalis. Carvedilol is also indicated to reduce cardiovascular mortality in clinically stable patients who have survived the acute phase of a myocardial infarction, as well as in the management of essential hypertension, alone or in combination with other antihypertensive agents. Generic Coreg contains same active ingredients (Carvedilol) as brand-name drugs and work the same way. The generic Coreg offers cost effective alternatives to patents in choosing their prescription drugs.  The Office of Generic Drugs, U.S. Food and Drug Administration, has determined the Ranbaxy formulations to be bioequivalent and have the same therapeutic effect as that of the reference listed drug Coreg(R) Tablets, 3.125 mg, 6.25 mg, 12.5 mg, and 25 mg, respectively, of GlaxoSmithKline.  Carvedilol tablets are manufactured by about 15 generic drug companies. All 15 pharmaceutical companies got approval on September 5, 2007. The following company’s applications were approved today (9/5): Actavis Elizabeth LLC; Apotex Inc.; Aurobindo Pharma Limited; Caraco Pharmaceutical Laboratories Limited; Dr. Reddy’s Laboratories; Glenmark Pharmaceuticals Limited; Lupin Limited; Mylan Pharmaceuticals Inc.; Ranbaxy Laboratories Ltd.; Sandoz Inc.; Taro Pharmaceutical Industries Ltd.; TEVA Pharmaceuticals USA; Watson Laboratories Inc.; and Zydus Pharmaceuticals USA Inc. The labeling of the generic products may differ from that of Coreg because parts of the Coreg labeling are protected by patents and/or exclusivity. Total annual market sales for Carvedilol Tablets were $1.6 billion and ranked30th top selling brand name drug by retail dollars in 2006. Overall I think it is a cost effective and safe alternative to expensive brand name drug product for patients.

Implications: This article is sad but consistent with overall increase use / abuse of opioids pain killers such as morphine, oxycodone, and hydrocodone. As a pharmacist & pharmaceutical consultant I think these are main reasons for alarming increase of opioids drugs use in America: The population is getting older. As age increases, so does the need for pain medications such as opiodsPharmaceutical companies have embarked on unprecedented marketing campaigns.A major change in pain management philosophy is now in its third decade. this leads to liberal use of opiodsMore people are abusing prescription painkillers because the medications are more available.I think that it is impossible to reliably measure painkiller abuse. Therefore we have to educate patients, physicians, medical community about the opiods us and abuse potential. We must help drug abuser such as Steve Dotson with medical treatment and other supports. Also we should improve DEA enforcement of law related opiods.

Analysis: This article is sad but consistent with overall increase use / abuse of opioids pain killers such as codeine, morphine, oxycodone, and hydrocodone. Based on recant DEA data More than 200,000 pounds of codeine, morphine, oxycodone, hydrocodone and meperidine were purchased at retail stores. That total is enough to give more than 300 milligrams of painkillers to every person in the country. In Appalachia, retail sales of hydrocodone -- sold mostly as Vicodin -- are the highest in the nation. Nine of the 10 areas with the highest per-capita sales are in mostly rural parts of West Virginia, Kentucky or Tennessee

As a pharmacist & pharmaceutical consultant I think these are main reasons for alarming increase of opioids drugs use in America:

1. The population is getting older. As age increases, so does the need for pain medications. In 2000, there were 35 million people older than 65. By 2020, the Census Bureau estimates the number of elderly in the U.S. will reach 54 million.
2. Pharmaceutical companies have embarked on unprecedented marketing campaigns. Spending on drug marketing has gone from $11 billion in 1997 to nearly $30 billion in 2005,
3. A major change in pain management philosophy is now in its third decade. Physicians now see pain management as an important ingredient in overcoming illness. This change in trend leads to liberal use of opiods.
4. More people are abusing prescription painkillers because the medications are more available. The vast majority of people with prescriptions use the drugs safely. But the number of emergency room visits from painkiller abuse has increased more than 160 percent since 1995, according to DEA
5. I think that it is impossible to reliably measure painkiller abuse. Therefore we have to educate patients, physicians, medical community about the opiods us and abuse potential. We must help drug abuser such as Steve Dotson with medical treatment and other supports. Also we should improve DEA enforcement of law related opiods.

I have followed this issue for my clients so please let me know if you need additional information from me.

Implications: The FDA has announced changes in the Warfarin label, recommending that a lower initial Warfarin dose should be considered for patients with certain genetic variations. Warfarin (Coumadin) is a commonly prescribed blood thinner with an exceptionally narrow safe-dosage range that varies dramatically from patient to patient. I think this label modification is one step closer to personalized medicine. Based on modern science and pharmacogenomics (the science that predicts a response to drugs based upon a person's genetic makeup) we can give the right drug in the right dose for the right patient. Overall as a pharmacist & pharmaceutical consultant I think, this labeling change highlights the opportunity to use genetic tests to improve initial estimate of a reasonable Warfarin dose for individual patients.

Analysis:  

The FDA has announced important changes in the Warfarin label, recommending that a lower initial Warfarin dose should be considered for patients with certain genetic variations. These labeling updates are based on an analysis of recent studies that found people respond to the drug differently based, in part, on whether they have variations of certain genes. Warfarin (Coumadin) is a commonly prescribed blood thinner with an exceptionally narrow safe-dosage range that varies dramatically from patient to patient. Warfarin is the second most common drug – after insulin –implicated in emergency room visits for adverse drug events. Historically, determining the correct dose often took multiple clinical visits and blood tests over several weeks or months. Until the correct dosing was established, patients were vulnerable to potentially deadly clotting events such as stroke, and side effects such as hemorrhages, excessive bruising or internal bleeding.

I think this label modification is one step closer to personalized medicine. Based on modern science and pharmacogenomics (the science that predicts a response to drugs based upon a person's genetic makeup) we can give the right drug in the right dose for the right patient. I strongly think that this will further enhance the safety and effectiveness of Warfarin.

Overall as a pharmacist & pharmaceutical consultant I think, this labeling change highlights the opportunity to use genetic tests to improve initial estimate of a reasonable Warfarin dose for individual patients. I also think that genetic testing may help optimize the use of Warfarin and lower the risk of bleeding complications from the drug.

Implications: Recently Johnson & Johnson announced the cutbacks to improve overall cost structure. Being a Pharmaceutical consultant, I follows industry trend. I think J&J is following the trend since Pfizer, AstraZeneca and Bristol-Meyers Squibb also announced that they would be trimming back staff this year. I think most cost saving will come from pharmaceutical division, HR, IT, and finance. Also I think they should better integrate its Cordis subsidiary. Overall I think J&J is being proactive for the future and adjusting to current drug development issues. I hope these actions will enable J&J to continue investing for future growth and profitability.

Analysis: Recently Johnson & Johnson announced initiatives that are expected to generate pre-tax, annual cost savings of about $1.4 in an effort to improve its overall cost structure. To further explain their initiatives, J&J announced that it would be laying off 3 to 4 percent of its global workforce. The most impacted will be pharmaceutical division, which faces numerous patent expirations, including top sellers such as migraine medication Topamax and antipsychotic Risperdal. J& J expected to file about 9 NDAs by 2010. Johnson & Johnson is the latest Pharma Company to announce cutbacks in operations. Pfizer AstraZeneca and Bristol-Meyers Squibb also announced that they would be trimming back staff. I think that these J&J cutbacks were not unexpected, in light major sales force layoffs at Pfizer and other companies. Pharma companies are trying to balance between maintaining a new structure and teams for products coming out, and maintaining existing products. Overall I think J&J is being proactive for the future and adjusting to current drug development issues. I hope these actions will enable J&J to continue investing for future growth and profitability.

Implications: As a pharmaceutical consultant, I think this IND will be novel groundbreaking treatment option for the treatment of bone diseases because it is one of first oral tablet formulation that enables oral absorption of gallium nitrate injection for treatment of cancer-related hypocalcaemia. Also this is unique collaboration of two different type drug discovery (Genta) & drug delivery companies (Emisphere). Both companies are similar size and active partner for this product. Phase 1 clinical trial that will examine initial safety and pharmacokinetics of G4544 in human subjects. I am hopeful that this oral tablet will be safe and effective since the active ingredient in G4544 has already demonstrated proof-of-concept activity in patients with multiple indications, including non-Hodgkin’s lymphoma, bone metastases, Paget’s disease, and osteoporosis.

Analysis:

Recently Emisphere & Genta announced the submission of IND (Investigational New Drug Exemption) for new drug known as G4544, Developed out of a joint collaboration announced last year.

G4544 is a new tablet formulation that enables oral absorption of the active ingredient contained in Ganite® (gallium nitrate injection), a drug that is marketed by Genta and approved in the U.S. for treatment of cancer-related hypercalcemia that is resistant to hydration.

Phase 1 clinical trial that will examine initial safety and pharmacokinetics of G4544 in human subjects. Genta will act as Sponsor of the IND and will direct the clinical development program.

Overall, I think this IND will be novel groundbreaking treatment option for the treatment of bone diseases because it is one of first oral tablet formulation that enables oral absorption of gallium nitrate injection for treatment of cancer-related hypocalcaemia.

Also this is unique collaboration of two different type drug discovery (Genta) & drug delivery companies (Emisphere). Both companies are similar size and active partner for this product.

I am hopeful that this oral tablet will be safe and effective since the active ingredient in G4544 has already demonstrated proof-of-concept activity in patients with multiple indications, including non-Hodgkin’s lymphoma, bone metastases, Paget’s disease, and osteoporosis.

Implications: Recently, Penwest Pharmaceuticals initiated Phase IIa study for oral Nalbuphine. Based on my extensive clinical experience in pain management, I think Oral Nalbuphine ER will be great addition oral treatment option for chronic pain patients. Currently this Nalbuphine is available in injection form and not suitable for chronic pain. Control release oral dosage form of this drug should be effective for chronic pain. Nalbuphine ER will be twice daily tablet, better option for chronic pain patent. This product will also improve compliance due to better deliver and pain management. Penwest Pharmaceutical is developing this product based on TIMERX technology. Penwest used same technology for Opana(R) ER (oxymorphone hydrochloride extended-release tablets). Overall based on Phase I study and Phase IIa study on Nalbuphine ER, I am very optimistic about this product. Please feel free to contact for additional information.

Analysis: Recently, Penwest Pharmaceuticals initiated Phase IIa study for oral Nalbuphine. This study is designed to assess the analgesic efficacy of Nalbuphine hydrochloride extended release tablet formulation (Nalbuphine ER). This study is a randomized, double-blind, placebo controlled design, with a forced weekly dose escalation and a total dosing period of 21 days in 216 patients.

Nalbuphine ER is a product being developed by the company for the treatment of chronic pain. It is designed as a twice-daily tablet and it uses the company's TIMERx drug delivery technology. Penwest used same drug delivery technology for Opana(R) ER (oxymorphone hydrochloride extended-release tablets).

Overall based on my knowledge, experience in pain management and Phase I study and Phase IIa study on Nalbuphine ER; I am very optimistic about this product. Please feel free to contact for additional information.

Implications: I think BEMA Fentanyl product will be very useful and novel method of delivering Fentanyl for the treatment of "breakthrough" cancer pain.

This clinical trial showed that the BEMA Fentanyl dosage form was convenient and comfortable to use for all patients and has dose linearity relationship with plasma level in patents.


Overall, based on my extensive experience with Fentanyl and related drugs, I think BEMA(TM) Fentanyl will play an important role in the future treatment of breakthrough cancer pain assuming FDA will approve this product

Analysis:  

BDSI (BioDelivery Sciences International, Inc.) is a specialty pharmaceutical company that is focused on developing innovative products to treat acute conditions such as pain.
Fentanyl BEMA(TM) drug delivery technology consists of a Fentanyl dissolvable, dime-sized polymer disc. This disk is applied to the mucosal (inner lining of cheek) membrane. BEMA(TM) discs deliver a rapid, reliable dose of drug across mucous membranes for given time.
BEMA(TM) Fentanyl is a lead product of BDSI. , a treatment for “breakthrough” cancer pain. Breakthrough cancer pain means episodes of severe pain which “break through” the medication used to control the persistent pain. Additional pain medication (same or different pain medicines) is required to control pain episode. Current treatments are not satisfactory and costly therefore large patients are under medicated. I think BEMA Fentanyl will satisfy unmeet need of Cancer patient.

This study consisted of Eighty (80) patients. This study was a double-blind, placebo-controlled. The results of this trial indicated that patients treated with BEMATM Fentanyl showed a statistically significant improvement in pain meaning a greater reduction in pain. This clinical trial showed that the BEMA Fentanyl dosage form was convenient and comfortable to use for all patients and has dose linearity relationship with plasma level in patents.