Astrazeneca Development Partner, Pozen, Inc., Submits New Drug Application For Pn400

AstraZeneca today announced that its development partner, Pozen, Inc., has submitted a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for VIMOVO (PN400) (enteric coated naproxen /esomeprazole magnesium) tablets, a product under investigation for the treatment of the signs and symptoms of osteoarthritis (OA), rheumatoid arthritis (RA) and ankylosing spondylitis (AS) in patients who are at risk of developing NSAID-associated ulcers. PN400 is a fixed-dose combination of enteric coated naproxen and immediate release esomeprazole.

The proposed trade name is VIMOVO, pending regulatory approval. Upon the FDA’s notification of acceptance of the NDA filing for PN400, a $10 million milestone payment from AstraZeneca will be payable to POZEN.

If approved, PN400 would offer a new arthritis treatment option for patients at risk of gastric ulcers, associated with non-steroidal anti-inflammatory drugs (NSAID). Nearly 27 million US residents and 140 million people worldwide suffer from osteoarthritis. The risk factors for NSAID-associated gastric ulcers include age (>/= 50 years), a documented history of gastric ulcers, or concomitant use of low-dose aspirin.

The NDA submission is based on data from a comprehensive clinical trials programme. The PN400 301/302 studies fully met their primary objective, showing subjects taking PN400 experienced significantly fewer endoscopically confirmed gastric ulcers compared to subjects receiving enteric coated (EC) naproxen. The primary endpoint was the cumulative incidence of gastric ulcers through six months. In each of the trials, approximately 400 subjects received either PN400 or EC naproxen 500mg, twice daily, over a six-month treatment period. Subjects underwent upper endoscopies at baseline and at one, three, and six months.

About VIMOVO (naproxen sodium/esomeprazole magnesium)

VIMOVO is an investigational product under co-development by AstraZeneca and POZEN, Inc. that combines the pain reliever naproxen (an NSAID) with esomeprazole, a proton pump inhibitor (PPI). VIMOVO is under investigation for the treatment of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis in patients who are at risk of developing NSAID-associated gastric ulcers.

About Osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease caused by the breakdown and eventual loss of the cartilage of one or more joints. Osteoarthritis is the most common form of arthritis and the most common cause of chronic pain, affecting nearly 140 million individuals worldwide, and impacting approximately 18% of women and 9.6% of men aged 60 and above. A combination of factors can contribute to osteoarthritis, including being overweight, aging, joint injury or stress, heredity and muscle weakness.Osteoarthritis commonly affects the hands, feet, spine or large weight-bearing joints, such as the hips and knees.

About Ankylosing spondylitis

Ankylosing spondylitis is a chronic inflammatory disease that primarily causes pain and inflammation of the joints between the vertebrae of the spine and the joints between the spine and pelvis (sacroiliac joints). Ankylosing spondylitis may also cause inflammation and pain in other parts of the body as well.

About AstraZeneca

AstraZeneca is a major international healthcare business engaged in the research, development, manufacturing and marketing of meaningful prescription medicines and supplier for healthcare services. AstraZeneca is one of the world's leading pharmaceutical companies with healthcare sales of US$ 31.6 billion and is a leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infectious disease medicines. For more information about AstraZeneca, please visit:www.astrazeneca.com

Source : www.pressreleasepoint.com

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FDA Approves Heart Drug After New Trials

The FDA has approved the antiarrhythmic dronedarone (Multaq) for treatment of atrial fibrillation and atrial flutter, the drug's developer announced today.

Dronedarone is the first drug approved in the U.S. that has shown a clinical benefit to reduce cardiovascular hospitalization in patients with those conditions.

Calling the drug's approval "exciting," Stuart Connolly, MD, of McMaster University in Hamilton, Ontario, and a principal investigator in the ATHENA trial of dronedarone, suggested that the drug's reduction in hospitalizations "could change the way we approach the management of [atrial fibrillation and flutter]."

The FDA rejected the drug in 2005 following cancellation of the ANDROMEDA trial after enrollment of only 627 of 1,000 planned patients because of "worsening heart failure in the dronedarone group [n=25 versus 12 (placebo), P=0.027]," said a sanofi-aventis press release.

But the ATHENA trial, reported in the Feb. 12, 2009, issue of the New England Journal of Medicine, found a 25% reduced risk of the primary outcome of hospitalization for cardiovascular events or death (P<0.001)>

In ATHENA, 71% of at-risk patients had no heart failure, while 29% were in NYHA class I-III with stable heart failure, and 24% had a reduction in cardiovascular hospitalizations or death from any cause. Because of the ANDROMEDA findings, however, dronedarone is contraindicated, in patients with class IV heart failure or class II-III with recent decompensation needing treatment, said a sanofi-aventis press release.

Dronedarone is available in a 400 mg tablet that should be taken twice daily at morning and evening meals. Common adverse reactions include diarrhea, nausea, vomiting, abdominal pain, weakness, and rash.

Source : www.medpagetoday.com

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Expect FDA Approval of AMAG Pharmaceutical's Feraheme

expects the U.S. Food and Drug Administration (FDA) to decide on the marketing application of AMAG Pharmaceuticals, Inc.’s (AMAG) Feraheme (formerly known as Ferumoxytol), designed for the treatment of iron deficiency in anemia patients with chronic kidney disease (CKD), including dialysis dependent and non-dialysis dependent CKD patients.

Anemia is a condition of abnormally low levels of red blood cells (RBCs) in the blood and hemoglobin. Hemoglobin is a protein present in RBCs that is responsible for transporting oxygen to the body tissues. Deficiency of iron is one of the reasons behind the development of anemia in CKD patients.

Kidney disease eventually leads to kidney failure, a condition in which the kidney fails to perform its functioning of removing wastes from the body in the form of urine. Regular dialysis is required when both the kidneys have stopped working. Dialysis is a medical procedure of removing impurities and waste products from the blood, when the kidneys are unable to do so.

Feraheme, the lead pipeline candidate of AMAG, is being tested for the treatment of iron deficiency in anemia patients with CKD and as an agent to improve the visibility of internal bodily structures (contrast agent) during magnetic resonance angiography (MRA) in peripheral artery disease (PAD) patients. MRA is a non-invasive medical imaging technique, which is used to produce detailed three-dimensional images of the blood flow in the blood vessels.

PAD is a condition that reduces the blood flow in the legs.

Anemia is a major problem associated with CKD. Iron replacement therapy, currently available in both oral and intravenous/IV (injected in the veins) formulations, is the existing standard treatment for anemic CKD patients. However, oral iron replacement therapies are associated with various side effects (like diarrhea and cramping) and the injectable products take a long time to be administered.

If successfully developed and approved, Feraheme could emerge as the preferred iron replacement therapy for anemia patients with CKD, promoting safety and faster administration. We estimate the peak revenue potential of the drug at approximately $450 million, or 49.08% of the company’s current market capitalization.

Potential Impact:

Feraheme, the lead pipeline candidate of AMAG, is under evaluation for the treatment of iron deficiency in anemia patients with CKD (including dialysis dependent and non-dialysis dependent patients) as well as a contrast agent for MRA in PAD patients. On May 25, 2008, AMAG entered into an agreement with 3SBio Inc. (SSRX), whereby SSRX obtained the exclusive rights to develop and commercialize Feraheme for CKD in China. In addition to this, AMAG is exploring potential partnership opportunities for the drug in other countries.

In December 2007, AMAG filed a New Drug Application (NDA) with the FDA for the approval of Feraheme for the treatment of iron deficiency in anemia patients with CKD. In October 2008, the company received a Complete Response Letter (CRL) from the FDA for the drug. In this letter, the FDA requested for additional information regarding the clinical trial data of Feraheme that had been submitted by AMAG and the company subsequently provided the relevant information to the FDA. However, in December 2008, the FDA issued another CRL to the drug. AMAG responded by resubmitting the NDA of Feraheme. The next crucial event for AMAG, the decision on the marketing application of Feraheme by the FDA, is expected by June 29, 2009.

CKD is characterized by a decline in the kidney functioning of an individual for a period of 3 months or more. Anemia, an under-recognized but characteristic feature of CKD, is associated with severe consequences such as cardiovascular disorders, hospitalizations and can even lead to death in the advanced stage CKD patients. In fact, anemia becomes more prevalent as the kidney functioning declines in the advanced stages, ranging from approximately 27% in the initial stages of CKD to 76% in the most advanced stages.

Anemia occurs due to iron deficiency in CKD patients, who require iron replacement therapy to manage their condition. Currently, iron replacement therapies are available in both oral and IV formulations. Oral iron replacement therapies suffer from the problem of being poorly absorbed in anemic patients and have a poor tolerability profile, thereby causing side effects like diarrhea and cramping, often resulting in discontinuation of treatment. Though IV therapies are far more effective than the orally administered ones, they also suffer from certain limitations.

Some of the existing IV therapies like Venofer from Fresenius Medical Care AG & Co. (FMS)/Vifor International, a subsidiary of Galenica AG, which is a Switzerland-based company, and Ferrlecit from Watson Pharmaceuticals, Inc. (WPI)/Sanofi-Aventis (SNY) need to be administered slowly and periodically in small dosages to meet the total dosage requirement of patients. Most patients require a total of 1,000mg Venofer to obtain treatment benefit, however, this 1,000mg cannot be administered in a single administration. In non-dialysis dependent anemic CKD patients, the total dosage of Venofer is divided into 5 sub-dosages (200mg each), with each sub-dosage requiring 5-10 minutes for administration. These 5 sub-dosages are given at 5 different occasions distributed over a 14-day period. In dialysis dependent anemic CKD patients, the total dosage of Venofer is divided into 10 sub-dosages (100mg each) and each sub-dosage requires 5-10 minutes for administration. All these 10 sub-dosages are administered at 10 different occasions.

Ferrlecit is only approved for dialysis dependent anemic CKD patients and has to be furnished at a dosage totaling 1,000mg to show treatment effect. However, the entire dosage of Ferrlecit can also not be administered in a single administration and is broken into 8 sub-dosages (125mg each), with each sub-dosage taking approximately 10 minutes (which sometimes extends to 1 hour) for administration. These 8 sub-dosages are given over 8 consecutive dialysis sessions.

Another disadvantage of the IV therapies is that they are associated with rare and life-threatening anaphylactic reactions (severe, life-threatening allergic reactions, which are characterized by symptoms such as low blood pressure, wheezing, vomiting and diarrhea). All these factors have left the market open for more effective treatment options in development for this condition.

Feraheme demonstrates many benefits over the currently available iron replacement therapies. Previous clinical trials indicate that Feraheme does not cause the side effects associated with oral iron replacement therapies. Unlike the inconvenient dosing schedule of the existing IV iron replacement therapies, Feraheme can be rapidly administered in two 17-second injections. Moreover, no cases of serious anaphylactic reactions have been observed in the clinical trials of Feraheme. Driven by these advantages, Feraheme could emerge as a therapy of choice for anemia patients with CKD. The U.S. IV iron replacement therapy market (currently approximately $570 million) represents an attractive opportunity for AMAG, with approximately 354,000 CKD dialysis dependent patients and 1.6 million CKD non-dialysis dependent patients, being currently eligible for Feraheme treatment. We believe Feraheme could generate peak revenues of approximately $450 million, or 49.08% of the company’s current market capitalization.

Expectations:

We expect the FDA to approve Feraheme for the treatment of iron deficiency in anemic CKD patients, including dialysis dependent and non-dialysis dependent ones by June 29, 2009.

In December 2007, AMAG submitted the marketing application of the IV formulation of Feraheme for the treatment of iron deficiency in anemic CKD patients. The filing was primarily based on the data from three Phase III efficacy and safety trials and one Phase III safety trial.

Across all the Phases of the clinical trials, a total of approximately 2,800 dosages of Feraheme had been administered. However, there were no cases of anaphylactic reactions and no incidences of any drug-related deaths reported in the Feraheme patient group. Additionally, throughout the clinical trials, only three (0.17%) out of the 1,726 Feraheme patients experienced serious adverse events like cardiac problems, while one (0.35%) among the 289 oral iron replacement therapy patients and one (0.13%) of the 781 placebo patients experienced serious adverse events.

On October 20, 2008, the FDA issued a CRL to Feraheme, which reflected their view that the drug was not ready for approval. In the CRL, the FDA requested for additional information regarding the clinical trial data submitted by AMAG. The agency also asked for certain clarifications regarding its inspection of one of the Phase III trial sites of Feraheme in addition to raising a question regarding a pre-approval inspection of AMAG’s manufacturing facilities. AMAG indicated that all of these issues were addressable and submitted its response to the CRL on the basis of the existing clinical trial data and stated that no additional trial was needed to be initiated. The FDA accepted the response to the CRL on November 13, 2008 and assigned Feraheme a new approval date of December 30, 2008.

However, on December 22, 2008, AMAG announced that it had received a second CRL for Feraheme. This time also the FDA had raised some additional queries regarding the pre-approval inspection of AMAG’s manufacturing facilities. Additionally, there were some questions regarding Feraheme’s labeling-related decisions. Though the company is seeking an FDA approval of Feraheme for the treatment of iron deficiency anemia in all CKD patients, patients who are on dialysis and patients who are not on dialysis, it is the FDA who has to decide on the final labeling of Feraheme. In the CRL, the FDA mentioned that it is yet to take a final decision regarding the labeling of the drug.

On May 1, 2009, AMAG declared that all the outstanding issues related to the manufacturing sites of Feraheme had been successfully and satisfactorily settled with the FDA. Additionally, the company stated that it had successful interactions with the FDA regarding the content of the label of Feraheme. Given that all the manufacturing issues related to the drug have been resolved, the company is optimistic that the FDA will be able to take a final decision regarding the labeling of Feraheme.

On May 12, 2009, AMAG announced that their response to the second CRL has been accepted by the FDA and the agency has designated it a Class I resubmission, assigning it a new approval date of June 29, 2009.

Class I resubmission deals with minor application deficiencies, such as labeling issues, commitments to perform post-marketing studies, safety updates and other minor clarifying information. Class I resubmission starts a new 60 days review cycle.
Based on the fact that the company succeeded in satisfactorily answering the FDA’s queries regarding the manufacturing of Feraheme, the major concern of the agency, which was highlighted in both the CRLs, we are optimistic about the company receiving approval this time for Feraheme by June 2009.

The Product:

Chronic kidney disease (CKD) patients often suffer from anemia, a condition of abnormal reduction in the number of red blood cells (RBCs) and hemoglobin (the iron-containing protein present in RBCs) in the body. Hemoglobin carries oxygen to the body’s tissues.
The production of RBCs depends upon two factors: firstly a hormone called erythropoietin, which is produced by the kidneys, and secondly iron. Erythropoietin, after being released by the kidneys, travels to the bone marrow (the soft tissue in the center of bones, responsible for the blood cell production) via the blood. Upon reaching the bone marrow, erythropoietin stimulates RBC production. An adequate concentration of iron is also essential for the bone marrow to produce the hemoglobin part of RBCs since iron is an integral component of hemoglobin.
Both erythropoietin and iron should work together to produce the required amounts of RBCs in the blood. An imbalance in the erythropoietin and iron levels leads to anemia.
The diseased kidneys in CKD patients do not produce the required amounts of erythropoietin. As a result, the bone marrow produces lesser amounts of RBCs, which is insufficient to meet the body’s RBC requirement. Additionally, CKD patients suffer from increased iron loss due to inadequate nutrition (which results in poor dietary iron intake), blood loss caused by multiple blood draws, dialysis (if needed), gastrointestinal bleeding and surgical procedures. Iron deficiency and an inadequate supply of erythropoietin together make patients anemic.
Anemic CKD patients are often treated with Erythropoietin Stimulating Agents (ESAs), like Amgen Inc.’s (AMGN) Epogen, to increase the production of RBCs. ESAs are synthetic versions of the natural erythropoietin and function in a similar manner to the natural hormone. The initiation of ESAs result in rapid increase in the production of RBCs. Besides erythropoietin, iron is another prime requirement for the production of RBCs. Thus, the rapid increase in RBC production on the initiation of ESAs involves an increased usage of iron in the body. CKD patients have low levels of iron in the body. Long-term usage of ESAs depletes the existing iron reserves in these patients and the consequent iron deficiency limits the effectiveness of ESAs. As a result, the majority of CKD patients require iron replacement therapy to replenish their iron levels.
Feraheme, an intravenously (IV) administered iron replacement therapy, works to replenish the iron levels, which is lost in anemic CKD patients with iron deficiency.
Advantages of Feraheme:

Avoids the Side Effects Associated with Oral Iron Replacement Therapies – Oral iron replacement therapies have limited efficacy and they do not adequately increase the body's iron levels in anemic CKD patients. Additionally, oral iron replacement therapies are poorly absorbed in anemic CKD patients, resulting in unwanted side effects such as diarrhea and cramping, often leading to the discontinuation of treatment. In contrast, the IV formulation of Feraheme provides greater amounts of iron in anemic CKD patients, while avoiding the side effects linked with oral iron replacement therapies.
Rapid Administration and Less Frequent Dosing – The existing IV iron replacement therapies (like Venofer from FMS/Vifor International and Ferrlecit from WPI/SNY) need to be administered slowly and in small dosages over several sessions to meet the body’s total iron requirement. The recommended dosage of Venofer is 1,000mg, which cannot be administered at a single go.
In non-dialysis dependent CKD patients, the total dosage (1,000mg) of Venofer is divided into 5 sub-dosages (200mg each), with each sub-dosage requiring 5-10 minutes for administration. The 5 sub-dosages are given in 5 different occasions within a 14-day period.
In dialysis dependent CKD patients, the total dosage (1,000mg) of Venofer is divided into 10 sub-dosages (100mg each), with each sub-dosage administration requiring 5-10 minutes. All these sub-dosages are administered in 10 different occasions.
Ferrlecit, which is approved only for dialysis dependent CKD patients, has a recommended dosage of 1,000mg. Like Venofer, Ferrlecit cannot be given in single administration. The total dosage is broken into 8 sub-dosages (125mg each), taking approximately 10 minutes (which sometimes can extend to an hour) for administration of each sub-dosage. These 8 sub-dosages are given over 8 consecutive dialysis sessions.

In contrast, Feraheme is rapidly administered in two 17-second injections, making it more patient friendly.

The Market:

Chronic kidney disease (CKD) is the gradual and usually permanent loss of kidney functioning, which occurs as a result of physical injury or a disease (such as high blood sugar or high blood pressure) that damages both the kidneys. This loss of kidney functioning is gradual that may take even months or years. In CKD, the tiny filters in the kidneys (called nephrons) are damaged and the kidneys ability to remove wastes from the body gets declined.

Based on the severity of the disease, CKD is divided into 5 categories ranging from Stage 1 to Stage 5. Stage 5 is the most severe condition, which is characterized by total or near-total loss of kidney functioning and patients requiring dialysis or kidney transplantation to stay alive.

Anemia, an abnormal reduction in RBCs, is a rational consequence of CKD. This is because the damaged kidneys are incapable of producing sufficient amounts of erythropoietin, a hormone stimulating RBC production. Thus, CKD patients are at high risk for developing anemia and the treatment of anemia in CKD patients is extremely important to keep them healthy.

To increase RBC production, anemic CKD patients are treated with ESAs. The production of RBCs also requires iron, thus increasing the utilization of the existing iron stores of the body. The continuous usage of ESAs initiates an increased usage of iron in the body, thereby causing a progressive reduction in the body’s iron reserves, resulting in an iron deficiency. This decreases the effectiveness of ESAs as a treatment of anemia. Additionally, blood loss caused by multiple blood draws, surgical procedures, dialysis as well as due to gastrointestinal bleeding, reduces the iron levels in CKD patients. Therefore, a majority of CKD patients eventually develop iron deficiency anemia, requiring iron replacement therapy.

Source : seekingalpha.com

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A New Drug to Lengthen Eyelashes

I can almost hear the voiceover... "Are pale, stumpy, thin lashes undermining your confidence and destroying your life? Ask your doctor about Latisse to see if you have Low-Bat Syndrome (LBS). And blink your way back to life."

From an actual press release about the prescription solution in December: "'LATISSE™ fulfills a significant and previously unmet need in the medical aesthetic marketplace with a product approved by the FDA that increases the growth of eyelashes, making them longer, thicker and darker,' said Scott Whitcup, M.D., Allergan's Executive Vice President of Research and Development." Apparently there is a condition called "eyelash hypotrichosis"--not having "adequate" eyelashes.

I'm sure this is a real thing--I know when I had chemo and my eyelashes jumped ship it was a weird, unfun thing that really did undermine my confidence. But, um, really? This is not just being marketed to those with a rare medical syndrome, but rather as an alternative to mascara (an admittedly imperfect product).

So now you can trade your racoon eyes for, wait for it, side effects or "safety information" (bolding mine): "LATISSE™ use may cause darkening of the eyelid skin which may be reversible. Although not reported in clinical studies, LATISSE™ use may also cause increased brown pigmentation of the colored part of the eye which is likely to be permanent. It is possible for hair growth to occur in other areas of your skin that LATISSE™ frequently touches... It is also possible for a difference in eyelash length, thickness, fullness, pigmentation, number of eyelash hairs, and/or direction of eyelash growth to occur between eyes. These differences, should they occur, will usually go away if you stop using LATISSE™." Plus it can cause redness and itching.

Perhaps even more distressing is that Latisse's spokeswoman is Brooke Shields. You can see her Latisse "before and after" shots here. The commercial is similar to any old Covergirl ad. So now we're adding more chemically mysterious junk to our bodies in the name of beauty? One that can also cause "ocular pressure"? And the lovely Brooke is so hard-up to promote this? C'mon, gal. We love you. Love us back and walk away from the campaign.

By : Valerie Reiss
Source : blog.beliefnet.com

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Covance Announces Integrated Radiolabeled Clinical Pharmacology Studies

Covance Inc. today announced its integrated radiolabeled clinical pharmacology studies in compliance with Food and Drug Administration (FDA) guidance on Metabolites in Safety Testing (MIST). Recent MIST guidance requires earlier human absorption, metabolism and excretion (AME) testing in support of Investigative New Drug/Clinical Trial Application (IND/CTA) submissions.

"Integrated human AME services are designed to help reduce the time and cost of drug development by integrating clinical pharmacology AME study conduct and data management services with bioanalytical chemistry and drug metabolism," said Robert Kochan, PhD, clinical pharmacology, Covance. "Our integrated service capabilities developed by our team of experts has made us the industry leader in integrated AME testing as we recently completed our 130th AME study."

The results of AME studies provide essential information about the disposition of a drug by direct characterization of the compound's pharmacokinetics and information related to AME characteristics. Stringent data requirements for AME studies demand experienced radiochemical and chemical analysis services to obtain definitive metabolite disposition data in humans.

Covance offers 24-hour turnaround of Good Laboratory Practices (GLP) sample radioanalysis and Good Manufacturing Practices (GMP) stability and release testing of dose formulations. With more than 130 AME studies completed, Covance's team of experts deliver integrated AME study services, including on site Authorized Nuclear Pharmacist-formulated doses; cGMP formulation testing; AME study conduct and analysis of parent compound; total radioactivity; pharmacokinetic interpretation; and metabolite profiling and identification.

Covance's clinical development services include Phase I-IV clinical trial support in more than 55 countries, including emerging markets across Asia Pacific, Central and Eastern Europe, and Latin America.

Source : news.prnewswire.com

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More data needed on Glaxo nausea drug

The U.S. Food and Drug Administration has rejected GlaxoSmithKline PLC's application to approve an experimental drug for nausea and vomiting, saying more data is needed.

The British drugmaker said Tuesday that it had received a "complete response letter" from the FDA regarding its application for casopitant. Glaxo applied to the FDA in May 2008 for approval to sell the drug for nausea and vomiting that occurs after surgery or is triggered by chemotherapy.

The FDA's Center for Drug Evaluation and Research issues complete response letters when staff have finished reviewing all the experimental and other data in a new drug application and there are outstanding questions or issues that bar approval of the product.

GlaxoSmithKline said in a statement that the company is reviewing the FDA's letter and will work with the agency to decide the next appropriate steps.

Company spokeswoman Lisa Behrens said the FDA is requiring specific, additional information in order to consider approval of casopitant.

Glaxo plans to sell the drug under the trade name Rezonic. It already sells a drug for nausea caused by chemotherapy and radiation therapy, Zofran, and tested Rezonic for its effectiveness in combination with both Zofran and a third drug, dexamethasone.

If approved, Rezonic would compete with a few similar drugs, including Whitehouse Station, Merck & Co.'s Emend, Tokyo-based Eisai Co. Ltd.'s Aloxi and New Jersey-based Par Pharmaceutical's Marinol.

Source : www.google.com

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Cytopia Lodges IND for JAK2 Inhibitor CYT387

Cytopia Ltd announced today that it has filed an Investigational New Drug Application (IND) with the US Food and Drug Administration (FDA) for its novel, potent orally active JAK2 inhibitor CYT387.

Following FDA review, the company intends to commence a Phase I/II trial for CYT387 in patients with myelofibrosis, a serious progressive and chronic condition where scar tissue develops in the bone marrow. CYT387 is expected to be the second Cytopia developed drug candidate in clinical studies and the first trialled in the United States, with the anticancer .

vascular disrupting agent CYT997 now in Phase II clinical studies in Australia.

Over-activity of the JAK2 enzyme is implicated in a variety of haematological conditions known as the myeloproliferative disorders (MPDs). This suite of conditions includes myelofibrosis, polycythemia vera and essential thrombocythemia. Cytopia has demonstrated that CYT387 inhibits the overactive JAK2 enzyme in an invivo preclinical model and in cells from patients with MPDs. This data suggests that the compound may exert a profound effect on the human disease.

Myelofibrosis results in a compromised ability of patients to produce sufficient blood cells and a reliance on organs other than the bone marrow, including the liver and spleen, to produce cells. Typical symptoms include an enlarged spleen and progressive anemia and poor overall survival.

"The filing of an IND for CYT387 is the culmination of a comprehensive preclinical development effort by the Cytopia Drug Development team," said Mr Andrew Macdonald, CEO of Cytopia. "Our deep knowledge of the JAK2 target has been integral to the design of this drug and the program is significantly bolstered by the intellectual property we hold over the JAK2 target."

The clinical utility of CYT387 is also expected to have broader applicability in diseases driven by disregulated JAK2 signalling, including some cancers and various inflammatory conditions. Cytopia is exploring the utility of CYT387 in these conditions.

Source : www.marketwatch.com

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New Novartis ‘Niche Drug’ Approved for Rare Genetic Disorder

Drug maker Novartis AG has gained Food and Drug Administration approval for a new drug that treats a rare genetic disorder which afflicts just a few thousand people in the world.

The drug, Ilaris, represents a change in course of sorts for drug companies, who have begun developing more new drugs that are designed to correct one or two genetic triggers which cause rare diseases rather than cranking out medications designed to treat millions of people afflicted with more common disorders.

It may sound counter intuitive to market drugs for so-called “niche diseases” that affect fewer people than other conditions, but by focusing on specific genetic-based disorders that can be easier to unravel and develop drugs to treat, Novartis and other drug companies are gambling on the belief that such an approach will pay off in the long run, according to a report in The Wall Street Journal.

Novartis hopes the approach to developing new drugs will one day blossom into a market as big as today’s blockbuster drugs. Ilaris is Novartis’ first venture into genetic trigger drugs.

The new way of developing drugs certainly doesn’t come cheap. In 2002, Novartis spent $4 billion to build a new research center in Cambridge, Mass. and hired hundreds of scientists to work there, according to the Journal report.

Novartis won’t say how much it will cost to produce Ilaris, but industry analysts say it is likely to be among the world’s most expensive drugs.


Rare Genetic Syndrome is Treated
Ilaris is delivered via a shot and treats a rare, genetic disorder called cryopyrin-associated periodic syndrome (CAPS). The syndrome is caused by a mutation in a single gene and there are just 300 known cases in the entire United States. Worldwide, there are maybe 7,000 world-wide, medical experts say.

People with CAPS produce too much interleukin-1, a protein that is associated with the immune system, and develop inflammation, chronic rash, joint pain, and fever. In the most serious cases, CAPS can lead to kidney failure, deafness, and even death. Ilaris and its rival drug, Arcalyst, prevent the disease by stopping production of the protein.


Broader Uses Are Possible
The makers of Ilaris and Arcalyst are considering asking for FDA approval to treat gout, a more common inflammatory condition that causes chronic joint pain. Clearing the drugs for broader uses would increase profits for the drugs.

Novartis also is working on other drugs that genetically target disease. Those drugs currently in development include AIN457 for psoriasis and an inflammatory disorder of the eye that could hit pharmacy shelves as early as 2010 and AFQ056, a Parkinson’s disease drug the company plans for a 2012 launch.

Source : www.attorneyatlaw.com

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Strativa's New Drug Application For Ondansetron Orally Dissolving Film Strip Accepted By FDA

Strativa Pharmaceuticals, the proprietary products division of a wholly owned subsidiary of Par Pharmaceutical Companies, Inc. , today announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for ondansetron orally dissolving film strip (ODFS). Strativa is seeking approval of ondansetron ODFS for the prevention of nausea and vomiting associated with highly- and moderately-emetogenic chemotherapy, radiotherapy and surgery.

The ODFS, a new oral formulation of ondansetron designed to rapidly dissolve on the tongue, was developed using MonoSol Rx' proprietary PharmaFilm(TM) thin film technology. In clinical studies, this formulation demonstrated bioequivalence to ondansetron orally disintegrating tablets (ODT), both with and without water. Pursuant to Prescription Drug User Fee Act (PDUFA) guidelines, Strativa expects the FDA will complete its review or otherwise respond to the NDA by the first quarter of 2010.

"We are very pleased with the acceptance of our NDA submission and look forward to cooperating with the FDA on its review," said John A. MacPhee, President, Strativa Pharmaceuticals. "We believe the quick dissolving film strip formulation of ondansetron offers a convenient and easy-to-administer option for managing nausea and vomiting associated with chemotherapy, radiotherapy and surgery."

Nausea and vomiting is a common side effect associated with chemotherapy, radiation and surgery. Left untreated, nausea and vomiting can have serious consequences such as exhaustion, dehydration and undernourishment, which can interfere with treatment and healing.

In June 2008, Strativa and MonoSol Rx entered into an exclusive licensing agreement under which Strativa acquired the U.S. commercialization rights to ondansetron orally dissolving film strip.

About Strativa Pharmaceuticals

Strativa Pharmaceuticals is the proprietary products division of Par Pharmaceutical, Inc. Strativa is committed to developing and marketing novel prescription drugs. Its initial focus is on supportive care therapeutics in HIV and oncology. Drawing on the specialty products expertise of its staff, Strativa possesses the resources to prepare products for commercialization and to help ensure their success after launch.

About Par Pharmaceutical

Par Pharmaceutical, Inc. develops, manufactures and markets generic drugs and innovative branded pharmaceuticals for specialty markets.

Safe Harbor Statement

Certain statements in this news release constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. To the extent any statements made in this news release contain information that is not historical, these statements are essentially forward-looking and, as such, are subject to known and unknown risks, uncertainties and contingencies, many of which are beyond the control of the Company, which could cause actual results and outcomes to differ materially from those expressed herein. Risk factors that might affect such forward-looking statements include those set forth in Item 1A of the Company's Annual Report on Form 10-K for the year ended December 31, 2008, in other of the Company's filings with the SEC from time to time, including Quarterly Reports on Form 10-Q and Current Reports on Form 8-K, and on general industry and economic conditions. Any forward-looking statements included in this news release are made as of the date hereof only, based on information available to the Company as of the date hereof, and, subject to any applicable law to the contrary, the Company assumes no obligation to update any forward-looking statements.

Source : www.medicalnewstoday.com

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OSI Pharmaceuticals Announces Acceptance Of Tarceva Supplemental New Drug Application For Review By The U.S. Food And Drug Administration

OSI Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has accepted for filing and review the supplemental New Drug Application (sNDA) for the use of Tarceva® (erlotinib) as a first-line maintenance treatment for patients with advanced non-small cell lung cancer (NSCLC) who have not progressed following first-line treatment with platinum-based chemotherapy. Based upon the March 17th receipt of filing the FDA Prescription Drug Fee Act (PDUFA) review date will be on or about January 18, 2010.

"We are pleased with the FDA's decision to review the data to evaluate Tarceva as a first-line maintenance therapy," stated Colin Goddard, Ph.D., Chief Executive Officer of OSI Pharmaceuticals. "This decision puts us one step closer toward accomplishing our goal of making Tarceva available earlier in the course of lung cancer treatment, offering a non-chemotherapy choice for all NSCLC patients in the maintenance setting."

The sNDA filing is based on a pivotal Phase III placebo-controlled, randomized, double-blind trial known as SATURN. On May 14, 2009, OSI announced data from the SATURN study, which was formally presented at the 45th Annual Meeting of the American Society of Clinical Oncology on May 31, 2009 in Orlando, Fla.

About SATURN

SATURN is an international, placebo-controlled, randomized, double-blind, Phase III study conducted by Roche that enrolled 889 patients with advanced NSCLC at approximately 160 sites worldwide. Patients were treated with four cycles of standard first-line platinum-based chemotherapy and were then randomized to Tarceva (150 mg) or placebo if their cancer did not progress. The primary endpoint of the study was progression-free survival in the overall population, as determined by investigators, and was defined as the length of time from randomization to disease progression or death from any cause. The co-primary endpoint was PFS in patients with EGFR positive tumors by IHC. Secondary endpoints included overall survival, safety and an evaluation of exploratory biomarkers, including EGFR mutations and K-ras mutations.

The study met both of its co-primary endpoints by demonstrating a statistically significant 41% improvement in the time patients live without their disease worsening (as measured by progression free survival, or PFS) compared with placebo (Hazard Ratio = 0.71, p-value <0.00001; pfs =" 0.69," hr="0.76," value="0.0148," n="359);" hr="0.68," n="525).">

Pre-planned biomarker analyses of tissue samples collected as part of the SATURN protocol provided important information on the potential role of EGFR mutations and K-ras mutations in predicting possible outcomes of Tarceva therapy in NSCLC patients. The subgroup analysis of patients whose tumors possessed an activating EGFR mutation and were eligible for analysis (n=49) demonstrated a statistically significant ten-fold increase in the time patients live without their disease worsening (as measured by PFS) for patients treated with Tarceva compared with placebo. The hazard ratio was 0.10 (p-value <0.0001). hr="0.78," n="388).">

There were no new or unexpected safety signals observed in the SATURN study. Adverse events were consistent with those observed in previous Tarceva studies in NSCLC, and included rash (49.2% with Tarceva versus 5.8% with placebo) and diarrhea (20.3% with Tarceva versus 4.5% with placebo). Dose reductions were necessary in 11% of the patients treated with Tarceva versus 1% of those treated with placebo. Discontinuations due to adverse events were necessary for 4.6% of the patients in the Tarceva arm versus 1.6% in the placebo arm.

About Lung Cancer

According to the American Cancer Society (ACS), lung cancer is the single largest cause of cancer death among men and women in the U.S. and nearly 159,390 Americans are expected to die from the disease in 2009. Most people with lung cancer are diagnosed with advanced stage disease that cannot be surgically removed or has spread to other parts of the body. The majority of people with advanced lung cancer survive less than one year. NSCLC is the most common type of lung cancer.

About Tarceva

Tarceva is a once-a-day pill that targets the EGFR pathway. Tarceva is designed to inhibit the tyrosine kinase activity of the EGFR signaling pathway inside the cell, one of the critical growth factors in NSCLC and pancreatic cancers. Tarceva is indicated as a monotherapy for patients with locally advanced or metastatic NSCLC whose disease has progressed after one or more courses of chemotherapy. Results from two multicenter, placebo-controlled, randomized Phase III trials conducted in first-line patients with locally advanced or metastatic NSCLC showed no clinical benefit with the concurrent administration of Tarceva with platinum-based chemotherapy (carboplatin and paclitaxel or gemcitabine and cisplatin) and its use is not recommended in that setting. In pancreatic cancer, Tarceva is indicated in combination with gemcitabine for the first-line treatment of patients with locally advanced pancreatic cancer, pancreatic cancer that cannot be surgically removed or pancreatic cancer that has spread to distant body organs.

Tarceva Safety

There have been infrequent reports of serious Interstitial Lung Disease (ILD)-like events including deaths in patients taking Tarceva. Serious side effects (including deaths) in patients taking Tarceva include liver and/or kidney problems; gastrointestinal (GI) perforations (the development of a hole in the stomach, small intestine, or large intestine); and severe blistering skin reactions including cases similar to Stevens-Johnson syndrome. Patients taking Tarceva plus gemcitabine were more likely to experience bleeding and clotting problems such as heart attack or stroke. Eye irritation and damage to the cornea have been reported in patients taking Tarceva. Women should avoid becoming pregnant and avoid breastfeeding while taking Tarceva. Patients should call their doctor right away if they have these signs or symptoms: new or worsening skin rash; serious or ongoing diarrhea, nausea, loss of appetite, vomiting, or stomach pain; new or worsening shortness of breath or cough; fever; eye irritation. Rash and diarrhea were the most common side effects associated with Tarceva in the non-small cell lung cancer clinical study. Fatigue, rash, nausea, loss of appetite, and diarrhea were the most common side effects associated with Tarceva plus gemcitabine therapy in the pancreatic cancer clinical study.

Source : www.medicalnewstoday.com

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Zicam, the FDA and Homeopathy

The FDA just warned consumers to stop using certain Zicam Cold Remedy products designed to be used in the nose. The agency said it has received more than 130 reports of loss of smell associated with the use of the products, which are available without a prescription.

The warning letter the agency sent to Matrixx Initiatives, which sells Zicam, illuminates a corner of the health-care world we don’t often mention on the blog: homeopathy.

According to this explainer from the National Institutes of Health, homeopathy is based on “giving extremely small doses of substances that produce characteristic symptoms of illness in healthy people when given in larger doses.” (The active ingredient in Zicam is a form of zinc.)

The NIH says that individual studies of homeopathy have had varying results, but adds that “systematic reviews have not found homeopathy to be a definitively proven treatment for any medical condition.”

Zicam is marketed as a “homeopathic medicine.” As the FDA’s warning letter makes clear, “many homeopathic drug products are manufactured and distributed without FDA approval.” But, the letter adds, the agency can intervene when there’s evidence a homeopathic drug may pose a risk to consumers. That’s what it’s doing in this case.

The warning letter to Matrixx says that, because of the possible risks, the FDA will enforce its standard new-drug approval requirements for the intranasal Zicam products. That means Matrixx will have to demonstrate to the FDA’s satisfaction that “based on adequate and well-controlled clinical investigations … [the] product is safe and effective for each of its intended uses.”

Update: Matrixx posted a statement that said the products are safe and don’t cause loss of smell. The company called the FDA action “unwarranted” and said it is “in the process of determining its response.” The affected products accounted for about 40% of the company’s net sales, the statement said.

Source : blogs.wsj.com

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FDA Flags Psychiatric Risks Of Asthma Drugs

New labels on popular asthma drugs like Merck's Singulair must highlight language about suicidal behavior, depression and anxiety seen in a small number of patients, federal regulators said Friday.

After 15 months of investigation, the Food and Drug Administration said Merck & Co. Inc., AstraZeneca and Cornerstone Therapeutics will have to raise label warnings about psychiatric problems reported by a handful of patients taking their drugs.

"Patients and healthcare professionals should be aware of the potential for neuropsychiatric events with these medications," the FDA said in a posting to its Web site.

A spokeswoman for Merck said the language already appears in Singulair's label, but will be raised to the "precautions" section. It's now listed in a section about various side effects reported by patients.

"We've been working with the FDA since Singulair came to market and every time we update the label it's in cooperation with them," said Merck spokeswoman Pamela Eisele.

Singulair was Whitehouse Station, N.J.-based Merck's best-selling product last year, with U.S. sales of $3.5 billion.

A spokesman for London-based AstraZeneca said new labeling on its drug would only mention two psychiatric problems: depression and insomnia.

A spokesman for Cary, N.C.-based Cornerstone Therapeutics had no immediate comment Friday evening.

FDA regulators last spring began reviewing a handful of reports about mood changes, suicidal behavior and suicide in patients who had taken Singulair. The agency also launched probes into other drugs in the class, including AstraZeneca PLC's Accolate and Cornerstone Therapeutics Inc.'s Zyflo.

Earlier this year, the agency said company studies of the three drugs did not show an increased risk of suicidal behavior, though they were not designed to detect such problems. An FDA spokeswoman said Friday the agency is monitoring ongoing reports of suicide and other psychiatric problems among patients.

"We did move this language to the 'precautions' section to highlight that we're continuing to see these things," said FDA spokeswoman Karen Riley.

The exact language of the labeling updates has not been released, but the FDA said it could mention a slew of psychiatric problems, including: "agitation, aggression, anxiousness, dream abnormalities and hallucinations, depression, insomnia, irritability, restlessness, suicidal thinking and behavior -- including suicide -- and tremors."

In general, the FDA has started notifying the public earlier about possible safety issues with drugs after the agency came under fire for acting too slowly on drugs like Merck's painkiller Vioxx, which was removed from the market in 2004 because it doubled the risk of heart attack and stroke.

Source : www.wdsu.com

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Liver Transplant Drug Linked to Increased Risk of Death

Liver transplant patients who were treated with the drug sirolimus (also called Rapamune) following surgery appear to be at increased risk of death, the Food and Drug Administration is warning.

New clinical trial data suggests that stable liver transplant patients who were switched from a calcineurin inhibitor (CNI)-based immunosuppressive regimen to treatment with sirolimus were more likely to die or suffer severe adverse reactions, the FDA said.
The clinical trial was conducted by Wyeth, the maker of sirolimus. Wyeth submitted the results of the study to the FDA on March 25, 2009, officials said. The trial compared stable liver transplant patients who were switched from a CNI-based therapy to sirolimus to patients who remained on the CNI-based regimen.

The FDA is advising transplant physicians and patients about the clinical trial findings and continuing to examine the study data. The agency may decide to order changes to the labeling of the drug to further warn users and their doctors of the risk of mortality, officials said.

The FDA also issued the following recommendations on how physicians should handle sirolimus treatment:

• Sirolimus is indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving kidney transplants.

• The safety and the efficacy of sirolimus as an immunosuppressant have not been established in liver or lung transplant patients. This information is in the Boxed Warning of the sirolimus label.

• The current Boxed Warning of sirolimus indicates that the use of sirolimus in combination with tacrolimus was associated with excess mortality and graft loss in a study in de novo liver transplant patients. Many of these patients had evidence of infection at or near the time of death.

• Therapeutic drug monitoring is recommended for all patients receiving sirolimus.

• Therapeutic drug monitoring should not be the sole basis for adjusting sirolimus therapy. Careful attention should be paid to clinical signs and symptoms, tissue biopsy findings, and laboratory parameters.

• Patients unable to take the tablets should be prescribed the sirolimus oral solution and instructed in its use.

• Patients should be counseled that sirolimus is to be taken by mouth, once a day, consistently and with or without food.

• Sirolimus tablets should not be crushed, chewed or split.

Source : www.attorneyatlaw.com

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MDRNA gets FDA nod for generic osteoporosis nasal spray

Shares of MDRNA Inc more than doubled after the company said U.S. health regulators approved its generic nasal spray to treat osteoporosis, adding that its partner Par Pharmaceutical Cos Inc had launched the product.

The calcitonin-salmon nasal spray is the copycat version of Miacalcin nasal spray that is marketed by Novartis (NOVN.VX) in the United States.

The nasal spray is indicated for the treatment of osteoporosis in females who have low bone mass, after five years or more of menopause, relative to healthy premenopausal females, Par Pharma said in a statement.

U.S. sales of Miacalcin were about $112 million in 2008, the company said, citing IMS Health data.

In March, Par agreed to buy MDRNA's abbreviated new drug application for the generic nasal spray and its cGMP manufacturing facility in Hauppauge, New York, for an upfront cash payment and profit sharing on sales of the drug for five years.

"Any revenue generated from that product will go into our RNA interference research programmes," MDRNA's spokesman Matthew Haines said.

However, Haines declined to give more details about the nuances of the profit-sharing agreement.

RNAi or gene silencing as a way to fight disease, is one of the hottest areas of biotechnology research and has attracted investment from a range of major drugmakers.

MDRNA currently has a liver cancer programme in preclinical stage development.

MDRNA shares touched a high of $3.55 before paring some gains to trade up about 90 percent at $2.94 Tuesday morning on Nasdaq. Shares of Par Pharma were up 1 percent at $14.70 on the New York Stock Exchange.

Source : www.reuters.com

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Morphotek(R), Inc. Announces FDA Acceptance for the Treatment of Solid Tu

Morphotek(R), Inc., a subsidiary of Eisai Corporation of North America, announced that the U.S. Food and Drug Administration (FDA) cleared its investigational new drug (IND) application to study MORAb-004 in the treatment of patients with solid tumors. MORAb-004 targets endosialin, a protein expressed on cells associated with tumors and tumor blood vessel cells. The IND became effective 30 days after its initial submission to the FDA by Morphotek.

Some researchers have demonstrated that endosialin, the target of MORAb-004, is necessary for the development of new blood vessels (a process called angiogenesis). New blood vessels are required to provide blood flow to tumors for growth. Endosialin is expressed on pericytes which are cells that surround the smallest blood vessels and are needed for the survival, migration and differentiation of small blood vessels.

"The mechanism of action of MORAb-004, the concept of disturbing the tumor environment, is novel in cancer therapy," said Martin D. Phillips, M.D., Morphotek's Chief Medical Officer. "We are pleased to be carrying out the Phase I study with one of the world's leading health care institutions to focus on treating solid tumors and continue clinical development of this potential new treatment."

MORAb-004, which targets the growth of endosialin-expressing cells in tumor blood vessels, will be used to treat patients with solid tumors. Other anti-angiogenesis drugs target tumor endothelial cells, rather than pericytes. Treatment with MORAb-004 offers an alternative means to suppress tumor angiogenesis and growth.

"MORAb-004 is another unique therapeutic antibody being developed by our company that is believed to inhibit tumor growth via a disease-associated pathway identified and studied by one of our collaborative partners," said Nicholas Nicolaides, President and CEO of Morphotek. "Targeting of pericytes is a novel strategy in the anti-angiogenesis field and we look forward to reporting the results of these studies."

Morphotek obtained exclusive rights to develop and commercialize this antibody worldwide from the Ludwig Institute for Cancer Research (LICR). The endosialin protein as well as a precursor monoclonal antibody specific for endosialin, which is related to MORAb-004, were discovered in Dr. Lloyd Old's laboratory at LICR.

Source : news.prnewswire.com

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FDA Considers New Psychiatric Drugs for Children

The U.S. government is considering clearing three blockbuster psychiatric drugs currently taken by adults for use in children and adolescents, the Associated Press reported.

The drugs are now approved to treat schizophrenia and bipolar mania, also known as manic depressive disorder, in adults.

The Food and Drug Administration said the drugs appear to work in adolescents, but reviewers worry about exposing youngsters to the medications' side effects, which include weight gain, high blood pressure and sleepiness.

"These risks are of particular concern because of the lifelong nature of these disorders," Dr. Thomas Laughren, the FDA director for psychiatric products, wrote in documents posted online, the AP reported.

The issues will be discussed at a meeting Tuesday, when outside experts will voice their opinions about the drugs' risks and benefits. The FDA usually follows its advisory panels' advice, the AP said.

The drugs -- made by Pfizer Inc., Eli Lilly & Co. and AstraZeneca -- are currently approved to treat schizophrenia and bipolar mania in adults. Together, they accounted for $7.4 billion in sales last year, according to IMS Health, the AP said.

Many physicians already prescribe these drugs to children and teens. While it is permissible for doctors to prescribe as they see fit, pharmaceutical companies can only promote the drugs for FDA-approved uses, the APadded.

Source : www.empowher.com

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Somaxon resubmits new drug application for insomnia drug

Somaxon Pharmaceuticals, a specialty pharmaceutical company, has resubmitted its new drug application to the FDA for Silenor for the treatment of insomnia.

The resubmission includes additional statistical analyses of the company's clinical data relating to the durability of subjective sleep maintenance efficacy. It also includes the results of the company's completed clinical trial of doxepin that evaluated the potential for electrocardiogram, or ECG effects.

The results of that clinical trial demonstrated that Silenor had no effect on QT interval prolongation when administered at 6mg or under exaggerated exposure conditions of 50mg. The FDA has indicated that the review cycle for the resubmission will be six months.

Richard Pascoe, president and CEO of Somaxon, said: "We are confident that the additional clinical efficacy data analyses included in the resubmission demonstrate sustained subjective sleep maintenance efficacy in adults. Based on those analyses, as well as the favorable results from our ECG study, we believe that the resubmission can support a determination by the FDA that Silenor be approved for the treatment of insomnia."

Source : www.tradingmarkets.com

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Still No Winner in Acute HAE; FDA Wants New Cinryze Trial

Another runner has stumbled on a regulatory hurdle on the race to get the first acute hereditary angioedema (HAE) drug to market.

In a complete response letter to ViroPharma Inc., the FDA asked for a new trial of Cinryze (C1-esterase inhibitor) in treating acute HAE attacks, citing a lack of robustness in data - but no safety concerns - from the placebo-controlled Phase III trial. Cinryze already has approval as a prophylaxis therapy, but ViroPharma had been hoping to secure the C1 inhibitor market in HAE for itself under the seven-year orphan drug exclusivity rule.

It looked like the drug might have a chance late last year when competing C1 inhibitor Berinert, from King of Prussia, Pa.-based CSL Behring, got a complete response letter of its own, leaving the space potentially clear for a Cinryze sweep. But the latest setback might, instead, prove a boon to CSL, which has since resubmitted its biologics license application for Berinert, though that company said no review date has yet been set.

That raises the question of whether Exton, Pa.-based ViroPharma will opt for the expense of another Phase III trial.

Analyst Joel Sendek, of Lazard Capital Markets, wrote in a research note that the firm most likely will initiate a new trial, though Liisa Bayko, an analyst with JMP Securities, said management had indicated Thursday morning that the company remained "undecided as to whether or not it will pursue an additional study."

Bayko, however, remained optimistic, predicting "little impact" of the complete response letter to Cinryze revenue projections.

Cinryze sales totaled $6.7 million in the first quarter. Lazard's Sendek is projecting full-year 2009 revenue to reach $61 million based on the prophylaxis label alone.

But, as the first product to hit the market for any use in HAE, Cinryze easily could be picked up for acute treatment use even if the company is unable to promote that indication. ViroPharma also recently got an expansion on the prophylaxis label to include a more convenient self-administration, which could increase the probability of off-label use.

An approval of Cinryze in acute treatment of HAE "would have been strategic in nature, as it would have effectively blocked CSL from entering the market," Bayko wrote in a research note, but the fact that patients and physicians already are familiar with the product gives it "a significant leg up from the competition, should there be any."

Investors seemed to agree, as shares of ViroPharma (NASDAQ:VPHM) were dinged a mere 9 percent in trading Thursday, losing 64 cents to close at $6.29.

But another potential competitor got a boost on the news. Shares of Cambridge, Mass.-based Dyax Corp. (NASDAQ:DYAX) gained 19 cents, or 11.6 percent, to close Thursday at $1.83.

Dyax received a complete response letter in late March for Kalbitor (ecallantide), a plasma kallikrein inhibitor that works via a different mechanism than a C1 inhibitor and, therefore, would not be kept off the market by a C1 inhibitor approval.

Dyax is working to resolve issues raised in the agency's letter, including a request for a risk evaluation and mitigation strategy and additional information relating to the chemistry, manufacturing and controls section of the BLA. No new trials were required. (See BioWorld Today, March 30, 2009.)

Also coming down the regulatory pipeline is Pharming Group NV's Rhucin, another C1 inhibitor. The firm, based in Leiden, the Netherlands, said in April that it was in pre-BLA meetings with the FDA. (See BioWorld Today, April 17, 2009.)

And Basingstoke, UK-based Shire plc has said it plans to conduct another pivotal study of icatibant, a bradykinin B2 receptor antagonist, in acute HAE attacks later this year in a second attempt to get the product on the market in the U.S.

The FDA rejected a new drug application for icatibant last year, though the drug subsequently was launched in Europe as Firazyr. (See BioWorld Today, April 25, 2008.)

The BLA for Cinryze initially was filed in mid-2007 seeking approval in both prophylactic and acute treatment indications. The FDA issued an approvable letter in early 2008, though no new trials were required at that time according to Lev Pharmaceuticals Inc., which had developed the product prior to the firm's acquisition last year by ViroPharma. (See BioWorld Today, Feb. 1, 2008.)

Most of ViroPharma's revenue comes from sales of Vancocin (vancomycin), the only approved product for treating Clostridium difficile-associated pseudomembranous colitis.

Despite having lost patent protection several years ago, Vancocin has been spared generic competition largely due to the FDA's cumbersome clinical trial requirements for generic vancomycin. But the agency has scheduled an advisory panel Aug. 4 to discuss bioequivalence recommendations for generic vancomycin products.

Vancocin also could face completion from a macrocyclic antibiotic in late-stage development at Optimer Pharmaceuticals Inc., of San Diego, which reported striking Phase III data in C. difficile-based infections last year showing that the drug surpassed the primary endpoint of noninferiority to Vancocin. Later data, however, showed no difference between the two drugs in treating the most virulent strain of C. difficile, which analysts had been hoping ultimately would give fidaxomicin a marketing edge over ViroPharma's drug.

Assuming no generic versions are approved this year, ViroPharma anticipates Vancocin sales of between $250 million to $270 million.

Source : www.bioworld.com

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FDA's Anti-Infective Drugs Advisory Committee Review of Restanza

Advanced Life Sciences Holdings, Inc. announced today that the FDA's Anti-Infective Drugs Advisory Committee voted in the majority that Restanza(TM) (cethromycin) demonstrated safety for the outpatient treatment of adults with mild-to-moderate community acquired pneumonia (CAP) (11 positive, 3 negative, 1 abstaining). However, the committee voted that Restanza did not demonstrate efficacy in the treatment of CAP (3 positive, 11 negative, 1 abstaining).

"We believe in Restanza's potential and remain committed to its development. We were particularly encouraged by the supportive comments of several members of the committee relative to their positive review of the safety profile of Restanza, the therapeutic need for more effective treatments for CAP and their interest in seeing the company pursue further development," said Dr. Michael Flavin, Chairman and CEO of Advanced Life Sciences. "As we have throughout the review process we will continue to work closely with the FDA as they complete their assessment of the Restanza new drug application (NDA)."

Although it is not binding, the Committee's recommendation will be considered by the FDA as it completes its review of Restanza's NDA in CAP. The FDA has established a Prescription Drugs User Fee Act (PDUFA) date of July 31, 2009 for the Restanza NDA.

Source : www.bio-medicine.org

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New era of U.S. tobacco regulation at hand

In a historic shift in public health policy almost half a century after the U.S. surgeon general first warned of the lethal dangers of smoking, Congress is poised to give the federal government sweeping new authority to regulate the manufacturing of cigarettes and other tobacco products.

The legislation, long resisted by the tobacco industry, could allow consumers to see for the first time what chemicals and other additives tobacco companies put in their products. It would empower the Food and Drug Administration to put new limits on harmful ingredients and prohibit tobacco companies from marketing "light" cigarettes.

And it would give the FDA new authority to enlarge warning labels and severely restrict full-color ads for cigarettes and other tobacco products.

Yet the victory, which eluded anti-tobacco advocates for decades, comes with challenges as well as promise, as federal officials are given never-before-used tools to control a product that is still linked to some 400,000 deaths every year in the United States.

Particularly tricky may be keeping up the momentum of the anti-smoking campaign even as regulators try to make cigarettes safer, an effort that could paradoxically make some smokers less inclined to quit.

"We just don't know what is going to happen," said Kenneth E. Warner, dean of the University of Michigan's School of Public Health who has studied tobacco use for decades. "This is uncharted territory." Nonetheless, the legislation - which has passed the House and is expected to clear the Senate in coming weeks - would effectively end an era in which the tobacco industry was largely exempt from the regulatory scrutiny that has been standard for food, drugs and other consumer products.

The bill culminates a decades-long campaign by advocates who have chipped away at the industry's power with taxes, multibillion-dollar lawsuits and state and local limits on where smoking is allowed.

"This would be the most significant change in the federal government's approach to tobacco in history," said Matthew L. Myers, president of Campaign for Tobacco-Free Kids, a leading national advocate of tougher tobacco regulation. "It would fundamentally change the way tobacco is marketed, advertised and sold in this country." In recent years, dozens of states and cities have passed "clean-air" regulations banning smoking in government buildings, bars, restaurants and other public places. Earlier this year, Congress passed the largest-ever increase in the federal cigarette tax, boosting it by 62 cents to $1.01 a pack to pay for an expansion in children's health insurance.

Today, an estimated 20 percent of adults in the U.S. smoke, down from 42 percent in 1965, a year after the surgeon general's office issued its first warning.

But the industry has repeatedly dodged more stringent limits, including basic regulation of what is in tobacco products. Tobacco companies went to court in the late 1990s to block a Clinton administration bid for FDA authority over tobacco.

"If you look at a box of macaroni and cheese, you can see what kind of dye has been used. All the ingredients are scrutinized to determine whether they are dangerous to consumers' health," said Gregg Haifley, a senior lobbyist for the American Cancer Society Cancer Action Network.

"Not so tobacco. It has remained virtually the only unregulated consumable product in America." Public health advocates say that has allowed companies to advertise "light" and "mild" cigarettes as safer alternatives when, in fact, the products contain harmful additives and induce many users to intensify their smoking.

Under the legislation moving through Congress - sponsored by Rep. Henry Waxman of California and Sen. Edward M. Kennedy of Massachusetts, both Democrats - the FDA would have the power to prohibit such claims.

The agency also would be able to ban most flavorings in tobacco products and place limits on addictive nicotine as well as other ingredients and byproducts generated when tobacco products are smoked.

Manufacturers would not be able to introduce new products unless they are reviewed by the agency and would face new regulations requiring their outdoor advertising and advertising in most retail locations be limited to black and white. Businesses catering only to adults, such as bars, would be exempted.

And the FDA would have the authority to require new warning labels on up to 50 percent of the front and rear panels of tobacco product packaging.

The bills do not permit an all-out ban on nicotine. They also exempt menthol from the flavoring ban.

Lawmakers made additional concessions to the industry by requiring the FDA to consider the economic impact of any new restrictions and giving tobacco companies nonvoting representation on a new scientific advisory panel.

Those compromises are not insubstantial, said Stanton Glantz, a longtime tobacco control advocate who heads the Center for Tobacco Control Research and Regulation at the University of California, San Francisco. "One thing one learns from dealing with tobacco companies is that the devil is in the details."

Glantz is among a handful of public health advocates who fear that tobacco companies will end up gaming the regulatory process to enhance the reputation of their products.

Altria - the parent company of industry leader Philip Morris, which might have an easier time maintaining dominance in a more regulated market - endorses the bill.

"Our goal, under the federal regulation, would be to design the best products we can for someone who wants to enjoy tobacco without the health risks," said company spokesman William Phelps. Other manufacturers oppose the legislation.

Several Republican lawmakers have also expressed concerns that tobacco products will be perceived as safer because they are regulated by the FDA.

There is some risk that could decrease smokers' motivation to quit, said Dorothy Hatsukami, associate director of cancer prevention and control at the University of Minnesota's Masonic Cancer Center. "We have to make sure that we are continuing to educate the public to let them know that even if these products have reduced toxicants, they are still harmful."

Source : www.baltimoresun.com

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