GATTEX of NPS & Nycomed met primary endpoint in pivotal phase III trial

The phase III study evaluating the efficacy and safety of Gattex or teduglutide of NPS Pharmaceuticals in patients with Adult Short Bowel Syndrome met primary efficacy endpoint.

About teduglutide

• Teduglutide is the generic name of Gattex. Teduglutide is a novel, recombinant analog of human glucagon-like peptide 2.
• Glucagon-like peptide 2 is released by the L-cell of the ileum in the presence of food. Glucagon-like peptide 2 has been shown to stimulate the brush-border enzyme activities in the intestine. In addition, it has been shown to reduce the mucosal cell death in the intestine. Other effects such as increase the growth of the intestine as well as nutrient absorption have been observed.
• Teduglutide being an analog of human glucagon-like peptide 2 is hoped to do what the natural substances do. Patients with short bowel syndrome often have poor quality of life. They often are not

Pfizer and Takeda signed co-promotion agreements

Pfizer entered into co-promotion agreements with Takeda Pharmaceutical to promote rheumatoid arthritis medications in Japan.

• The first co-promotion agreement is the extension of its previous agreement under which Takeda is now able to co-promote Pfizer's Enbrel (or etanercept) for its use in Rheumatoid Arthritis for a longer period of time in Japan.  The previous agreement was signed between Takeda and Wyeth (which is now part of Pfizer).

• About Enbrel:
• Enbrel or etanercept is a tumor necrosis factor alpha inhibitor. It binds to the TNF-alpha, which plays an important role in inflammatory activities, to reduce the inflammation. Rheumatoid arthritis is characterized by high inflammatory activity. As a result, etanercept can be used to reduce the inflammation.
• Enbrel has been approved in over 80 countries.
• Pfizer and Amgen has co-promotion agreement that is to expire in October 2013 to co-promote

First Radiology Application - Mobile MIM - has been approved by the FDA

One of the coolest thing ever yet? (I'm sure it will be topped but this is just way too cool at least for folks living in the US!)

I remember when Apple first announced the iPad arrival, I was hoping the medical community would catch on the fever. How cool will it be to look at the patients' notes/labs/reports on the touch screen devices and make notes on them?

It seems that many people have resonated with me because its usage in medical community has increased. And now the first diagnostic radiology application to be used in the iPad and iPhone has been approved by the FDA to allow physicians to view medical images on these “handheld” devices. (Side note: on the

Makena of Hologic has received the approval from the FDA

Makena of Hologic has received the approval from the FDA to be used in patients at high risk of having preterm birth due to history of having lateast one sponteanous preterm birth . However it will probably be marketed by KV Pharmaceuticals according to the agreement signed between Hologic and KV Pharmaceuticals in 2008. (See below for more details)

About Makena

• Makena is the brand name of hydroxyprogesterone caproate. The drug has been assigned different brand names over the years. Progesterone is a natural hormone produced by the ovaries (and the placenta during pregnancy).  Its level often rises in pregnancy.  Low level of progesterone has been associated with risk of having a miscarriage. As a result, supplementing patients with synthetic progesterone might help decrease this risk in patient who has had miscarriage in the past.

• As stated above, the indication for Makena is very specific. If you look at what I have written later on, there are other risk factors that put patients at high risk of giving pre-term births. With Makena, it can only be used in

Regorafenib of Bayer received Orphan Drug Designation

Regorafenib of Bayer received orphan drug designation for the treatment of Gastrointestinal Stromal Tumors from the FDA.

About regorafenib

• Regorafenib is an oral multikinase inhibitor. It can bind to different receptors which take part in endothelial vascular growth as well as other angiogenesis processes (meaning cell growth).  Once binds, it will inhibit ligands from binding to respective receptors and hence inhibit the signaling cascade that often leads to cell proliferation. 
• Several kinase receptors have been found to be inhibited by regorafenib are Vascular Endothelial Growth Factor Receptors and TIE2 receptors.  Other oncogenic kinases have been shown to be inhibited by regorafenib are RAF, RET and KIT. As a result, it potentially can inhibit cancer growth.

Implication of orphan drug designation

• Once given the orphan drug, Bayer will have a seven-year market exclusivity for this indication

Sunovion has launched Once-daily Latuda or lurasidone HCl

Sunovion has official launched Latuda or lurasidone in the US.  The medication is now available in US pharmacies nationwide. Latura was originally approved in the US on October 28, 2010. 

• Sunovion Pharmaceuticals is a US subsidiary of Dainippon Sumitomo Pharma Co.
• Lurasidone is manufactured by Bushu Pharmaceuticals (now under the management of TMC Buyout 1 Co. Ltd which is managed by Tokio Marine Capital Co., Ltd.)

About lurasidone or Latuda

• Lurasidone is an atypical antipsychotic that has been approved to be used in the treatment of schizophrenia in adult patients.
• Currently, the exact mechanism of how lurasidone work is unknown.  It's hypothesized that it works through antagonizing the central dopamine Type 2 and serotonin Type 2 receptors.
• Lurasidone is metabolized mainly through CYP3A4.  As a result, other medications that either inhibit or

AV-299 of AVEO has been given a nonpriorietary name flictazumab

It's always nice to learn how to pronounce a new drug name. It's a different language of its own.

AVEO Pharmaceuticals has received the official USAN (United States Adopted Names) for its agent AV-299.  AV-299 will have the nonprioprietary generic name "ficlatuzumab" (pronounced as fye" kla tue' zue mab).

About AV-299
AV-299 is a novel molecule that is discovered within AVEO Pharmaceutical using its Human Response Platform (HRP).  Based on the name, it's a humanized monoclonal antibody that targets the hepatocyte growth factor in the HFG/c-MET pathway.  Hepatocyte growth factor can bind to c-Met receptor which once activated will increase cell proliferation and wound healing.  However, in the case of uncontrolled replication, cancer development and metastasis could potentially develop. 

Current development:
A Phase II trial evaluating the use of AV-299 in combination with gefitinib against gefitinib monotherapy (the generic name for Iressa of AstraZeneca) has been initiated in patients with non-small cell lung cancer.  The company expects to have the top of the line data results in late 2011.

Agreement
Even though a collaboration with Schering Corporation (now Merck) was developed in April 2007, in December 2010, AVEO has regained worldwide rights to develop and commercialize AV-299.

Hospira received approval from the FDA to market topotecan powder for solution for injection

The FDA has approved the ANDA for topotecan injection submitted by Hospira.  Hospira plans to launch the product by the end of February.  The product will be available at a concentration of 4 mg / 4ml.

Topotecan is the generic name for Hycamtin® marketed by GlaxoSmithKline.  

GSK is currently marketed Hycamtin in two formulations: capsule and lyophilized powder for solution for injection. 

Generic topotecan has been in the market but it is only available in the lyophilized powder for solution for injection formulation.  These are marketed by Three Rivers Pharmaceuticals, APP Pharmaceuticals and Sagent Pharmaceuticals.

About topotecan

• Topotecan is a semi-synthetic derivative of camptothecin.  It works to inhibit topoisomerase I which is an important enzyme that cuts one strand of the DNA.  In normal situation, the cut DNA will be able to ligate or get back to one another.  However, in the presence of topotecan which inhibits the topoisomerase I, the ligation cannot occur and lead to DNA damage.  Hence, this lead to cell deaths.

Different formulation of topotecan is approved for different indication:

• For the capsule formulation: topotecan is indicated for use in the treatment of relapsed small cell lung cancer patients who had prior complete or partial response and are at least 45 days from the end of the first-line chemotherapy
• For the lyophilized powder for solution for injection: It is indicated for the treatment of metastatic carcinoma, small cell lung cancer.  It can also be used in combination with cisplatin to be used in stage IV-B, recurrent, or persistent carcinoma of the cervix.  For more detail information, you can look at the product insert.

Valeant Pharmaceuticals acquired rights to non-ophthalmic formulation of Zovirax in the US and Canada

Valeant Pharmaceuticals through its subsidiary, Biovail Laboratories Interational SRL has acquired all US and Canadian rights to non-ophthalmic topical formulation of Zovirax or acyclovir of GlaxoSmithKline with $300 M.

Zovirax were marketed by GSK and BTA (which is a subsidiary of Biovail - which eventually means that is is part of Valeant Pharmaceuticals in the US). 

By GSK:

• Zovirax is marketed in 3 different formulations: capsules, tablet and suspension

By BTA:

• Zovirax is marketed in 2 different formulations: ointment and cream

About Zovirax

• Zovirax is the brand name for acyclovir (its generic has already been available and marketed by many different companies.  However, generic Zovirax ointment and cream have not been available in the US yet).
• Acyclovir is a synthetic purine nucleoside analogue.  As the molecule implies, it mimics purine nucleoside and interferes with the replication of viral DNA by binding to thymidine kinase (of herpese simplex virus type 1 and 2 as well as varicella-zoster virus).  Thymidine kinase converts acyclovir into acyclovir-monophosphate which eventually gets converted into acyclovir-triphosphate.  Acyclovir triphosphate once incorporated into the viral DNA will terminate the growing viral DNA chain.  In addition, also competively inhibit viral DNA polymerase in addition to its ability to inactivate viral DNA polymerase.
• Acyclovir is actually a very effective medicine in the treatment of herpes simplex virus.

My note: This transaction will give Biovail a larger market share of Zovirax in the US and expand its presence in Canada. However, due to the competing generics, I wouldn't expect profit will be very high or will be a market changer.

Vyvanse is now approved for use in a new ADHD patient group in Canada

Vyvanse or lisdexamfetamine of Shire has been approved for the treatment of attention deficit hyperactivity disorder in adolescent and adults in Canada by Health Canada.

Although this is the same indication as before, Vyvanse now can be used in a new patient population.  In 209, it was approved for use in ADHD patients whose age ranges from 6 to 12.  This new approval will expand its

Update on necitumumab of Lilly and Bristol-Myers Squibb

First of all, Happy Lunar New Year if you celebrate Lunar New Year where you are!  Whether it's a year of a rabbit or a year of  cat (depending on where you from), Pharmapodia wish you a successful year ahead! :)

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With this, it's unfortunate but I'm going to talk about a trial that has been stopped on Feb 2nd, 2011.

Lilly and Bristol-Myers Squibb announced that it has stopped the enrollment of one of the phase III trial susing necitumumab for the treatment of lung cancer.

The phase III trial is Called INSPIRE.  It's a randomized, multi-center (global), open-label study comparing the safety and efficacy of necitumumab in addition with Alimta (pemetrexed) and cisplatin against the combination of Alimta and cisplatin as first line treatment in patients with advanced non-small cell lung cancer.

The decision came after the independent Data Monitoring Committee (DMC) found that patients who were being treated with in the experimental arm (necitumumab, Alimta and cisplatin) appeared to have an increase risk of developing thromboembolism (which means blood clot).  As a result, no new or recently enrolled

The FDA issued a complete response letter in regard to the new drug application submitted by Orexigen for Contrave.

The FDA issued a complete response letter denying the approval of the new drug application submitted by Orexigen for Contrave on Monday, Jan 31, 2011.

And if you have followed the stock market, Orexigen has taken a massive plunge within a day going from $9.2 to around 2.7 (approximately 70-71% drop in value! NASDAQ:OREX).  Its price has been hovering around the $2.5-$2.8 territory. 

If you remember, it was news back in December when the FDA panel recommended the approval of Contrave under a condition that a large clinical trial would be needed to study its cardiovascular effect.

Isis initiated phase I trial of ISIS-FXIRx

The phase I trial using ISIS-FXIRx of ISIS has been initiated. 

About FXIRx

• ISIS-FXIRx is an antisense drug that is designed to treat clotting disorder by inhibiting factor XI production.  Factor XI is part of an intrinsic coagulation cascade.  ISIS-FXIRx will bind to the mRNA of factor XI and inhibit A decrease in factor XI concentration will lead to a lesser amount of activated factor XI.  Activated factor XI is a protease which in turn will activate factor IX which will impact the rest of the coagulation cascade.  As a result, this would reduce blot clot.   

Concert Pharmaceutical and Walter Reed Army Institute enter into a CRADA

Concert Pharmaceutical and Walter Reed Army Institute enter into a Cooperate Research and Development Agreement (CRADA) to perform clinical testing on compound developed using Concert’s deuterated chemical entity platform (DCE Platform).  The compound is aimed to provide seizure protection associated with traumatic brain injury (TBI).  

Under the agreement, the cost to perform preclinical efficacy evaluation of the novel compound derived from DCE Platform will be shared between both parties.  The compound will be tested in the preclinical model of brain injury of WRAIR.  It will also work to evaluate the compound for the potential treatment in brain diseases and injury.

Genzymes and its transaction

Genzyme and Sekisui Chemical Co.

• Genzyme announced that it has completed the sale of its Diagnostics Business to Sekisui Chemical Co. Ltd for a $256M in cash. In addition to purchasing all of the assets of the above business, both companies have entered into a supply agreement under which Sekisui Chemical will provide Genzyme with enzymes that are part of the production of imiglucerase or Cerezyme.  Cerezyme is an analogue of the human enzyme beta-glucocerebrosidase that is indicated for the treatment of Type 1 Gaucher disease in patients having one of the following conditions: Anemia, thrombocytopenia, bone disease, hepatomegaly or splenomegaly.
• Sekisui Chemical Co. plans to keep all positions at the Diagnostic Business intact.

Genzyme and International Chemical Investors Group (ICIG)

• In the same press release, Genzyme has entered into a purchase agreement with International Chemical Investors Group or ICIG.  An intermediate business of Genzyme will be acquired by an affiliate of ICIG.  No financial term is disclosed but the transaction is due to close in the first quarter of 2011.  ICIG will rename the newly acquired business as Corden Pharma Switzerland LLC.  It plans to maintain the operation at the manufacturing facility in Liestal, Switzerland and retains approximately 120 employees once the acquisition is complete.   
• Under the agreement, Genzyme enters into a supplying contract with ICIG under which it will be purchasing material needed for the production of eliglustat tartrate – an investigational compound that is being studied in phase III clinical trial for the treatment of Type 1 Gaucher Disease – from ICIG in the next five year. 
•  Both companies have also agreed to let ICIG supply materials needed to manufacture compounds for other treatments that are in early stages of developments.  Neo-GAA, an investigational product in preclinical development to be used as potential treatment of Pompe Disease, is also included in this contract.

Carfilzomib of Onyx gets Fast Track Designation

The FDA has issued a fast track designation to carfilzomib of Onyx.  Under this designation, carfilzomib is entitled to go through an accelerated approval process.  Through this process, Onyx is allowed to submit the New Drug Application for carfilzomib on a rolling basis.  This means that Onyx can submit data for each section of the New Drug Application separately rather than waiting to complete the entire application for submission.  The FDA will review its sections as they are submitted and this will speed up the NDA review process.

Up until now, Onyx has submitted to the FDA the non-clinical section of carfilzomib.  The complete NDA submission is expected in mid-2011.

About Carfilzomib

• Carfilzomib is a proteasome inhibitor.  It has an orphan drug status for its use in the treatment of multiple myeloma.
• The phase III clinical trial called ASPIRE investigating thesafety and efficacy of using combination of lenalidomide and low dose dexamethasone with or without carfilzomib in patients experiencing relapsed multiple myeloma.  The trial design and analysis were approved by both the FDA and EMA.
• In addition, it is also being studied in another phase III trial called FOCUS to investigate its use in patients with relapsed and refractory myeloma in Europe. 
• Carfizomib is also currently being studied to be used as treatment in advanced solid tumors in a phase 1b/2 study.