Sprycel of Otsuka and BMS gets additional indication as the treatment of adult patients with newly diagnosed Philadelphia positive chronic myeloid leukemia in chronic phase

Sprycel of Bristol Myer Squibb and Otsuka Pharamceutical is now approved to be used for the treatment of adult patients with newly diagnosed Philadelphia positive chronic myeloid leukemia in chronic phase in the US.  

Chromic myeloid leukemia is a slow-growing type of leukemia.   Philadelphia chromosome is condition in which patients' chromosomes (9 and 22) were recombined inappropriately and lead to defective BCR-ABL genes which send signals that lead to the overproduction of white blood cells.  CML can affect both adults and children but higher incidence is observed in adult population.

Normal white blood cell values is 4 to 11 x 10^9 / L.  Patients with chronic myeloid leukemia often have uncontrolled number of abnormal white blood cells production. Hence, their white blood cell count will be higher than this.

Sprycel or dasatinib is originally approved in 2006.  Dasatinib is a kinase inhibitor that can inhibits BCR-ABL, SRC family, c-KIT, EPHA2, and PDGFR-beta.  It is predicted to bind to multiple conformations of the ABL kinases.

Sprycel was discovered and developed by Bristol-Myers Squibb.  BMS and Otsuka are collaborative partners in the commercialization of Sprycel in the US, Japan, and major EU countries.  

It was approved originally through the accelerated FDA approval process in 2006 as the treatment for adults for all phases of Ph+ chronic, accelerated, or myeloid or lymphoid blast phase (CML) with resistance or intolerance to prior therapy including Gleeve.  In 2009, the FDA granted Sprycel its full approval.

Sprycell is now indicated for the following:

• Chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib 
• Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy 
• Newly diagnosed Philadelphia-chromosome positive chronic myeloid leukemia (Ph+CML) in chronic phase. The effectiveness of SPRYCEL is based on cytogenetic and major molecular response rates. The trial is ongoing and further data will be required to determine long-term outcome

 Source - BMS
Source  - Leukemia

Latuda or lurasidone is now approved to be used as treatment of schizophrenia in adult patients

The FDA on Oct 28, 2010 has approved the use of once a day Latuda or lurasidone tablets to be used as first line treatment of schizophrenia in adult patients.

Patients diagnosed with schizophrenia often exhibit symptoms such as hallucinations, delusions, disorganized thinking, lack of energy, problems with memory, attention, and ability to plan, organize, and make decision.

Lurasidone is an atypical antipsychotic developed by Sunovion Pharmaceuticals.  According to the package insert, as with other atypical antipsychotic, the exact mechanism of lurasidone is unknown.  However, it is suggested that it works through a combination of central dopamine Type 2 (D2) and serotonin Type 2 (5HT2A) receptors.

The drug was approved based on data from more than 40 clinical trials using LATUDA for the treatment of schizophrenia in approximately 2,700 patients.

As with other atypical antipsychotic, Latuda also carries a boxed warning

• Increased mortality in elderly patients with dementia-related psychosis (Latuda is not approved to treat patients with dementia-related psychosis).

Sunovion Pharmaceutical plans to launch the product in February 2011.



Sunovion Pharmaceutical based on Marlborough, Mass is a wholly-owned subsidiary of Dainippon Sumitomo Pharma.  Dainipon is a Japanese company that markets pharmaceutical, animal health and food and specialty products. 
 It is also important to note that atypical antipsychotic often exhibits many adverse side effects such as:

• extrapyramidal syndrome (not as much as other antipsychotic + it's often related to dose and duration)
• neuroleptic malignant syndrome (rare but has been observed)
• increase production of prolactin (milk production)
• weight gain, increase serum lipid concentration, diabetes, hypertension (metabolic disorders: very prominent) 
• Others.  

However, the frequency of these adverse effects varies from one atypical psychotic medication to another atypical psychotic medication.

For example: Extrapyramidal symptoms are often characterized as repetitive and involuntary muscle movements.  Extrapyramidal symptoms can be classified as either acute or tardive.

• Acute conditions are: dystonia, akathisia and parkinsonism,
• Tardive conditions are: tardive dyskinesia and tardive dystonia.  these conditions tend to be permanent.

Atypical antipsychotics often are employed as treatment of schizophrenia because it reduces the risk of developing extrapyramidal symptoms.

• In atypical medication, acute conditions are rare.  However, tardive conditions are often developed when patients are using atypical antipsychotic long term.  In addition, each drug within the atypical antipsychotic class carries different risk profile in developing EPS.  

• For example: aripiprazole has low potential to cause EPS but asenapine has higher potential to cause EPS.

Although atypical antipsychotic carries its own risk and its use needs to be cautious in specific population (e.g. diabetic, patients with lipid disorders), it is still a good treatment when appropriate interventions are employed in case of adverse events.

Press Release

Teva acquires Theramex,a women health and gynecology diivision of Merck

Theramex, women’s health and gynecology division of Merck KGA based in Monaco, is sold to Teva for 265M EU.  

Both Merck and Teva have signed an agreement under which Teva will acquire 100% shares of Theramex S.A.M (of Monaco) and Theramex S.p.A of Italy.  Also under the agreement, Merck will be entitled to receive certain performance-based milestone payments.  Teva has rights to distribute Theramex products in certain countries including Spain and Brazil while Merck Serono still has rights to continue distributing Theramex products in certain other countries.

Currently, Theramex markets women health’s products in 50 countries around the world. Its portfolio landscapes target gynecology, osteoporosis, peri-menopausa, menopause and contraceptives. 

Several marketed Theramex products are: Orocal, Colpotrophine, Lutenyl, Monazol, Estreva, Antadys and LeelooGe. 

Now part of Teva, Theramex is considered to be a partner with Merck and Co in the development of a new oral contraceptive containing nomegestrol acetate (2.5 mg) and 17 beta-estradiol (1.5 mg).  The new oral contraceptive is currently being registered in Europe.

Teva is one of the leaders in the generic market.  Its acquisition of Theramex will expand its portfolio in women health’s products and its presence in European countries. 

Source - Merck

AstraZeneca filed a suit against Watson in regard to its NDA for rosuvastatin zinc

Watson files a new drug application to seek US FDA approval of rosuvastatin zinc 5, 10, 20 and 40 mg tablets.  Rosuvastatin zinc is a new salt formulation of Crestor, rosuvasatin calcium, marketed by AstraZeneca.  

Rosuvastatin is a HMG-CoA reductase inhibitor.  HMG-CoA reductase is an important enzyme that is used to make mevalonate, a precursor of cholesterol.  As a result, inhibition of HMG-CoA reductase leads to reduction of cholesterol production.

AstraZeneca has filed suit against Watson to prevent the commercialization of Watson's product  prior to Crestor or rosuvastatin calcium's patent RE 37,314 expired.  Originally, rosuvastatin calcium was set to be expired in Jun 12, 2012.  RE37,314 was originally issued to Shionogi in 2007 to extend its original patent (approved in 1993) by 1305 days from June 12, 2012.  Hence, the new patent expiration date is Jan 08, 2016.  

Several of other HMG-CoA reductase inhibitors are

• atorvastatin
• simvastatin
• fluvastatin
• lovastatin
• pitavastatin
• pravastatin

Currently, rosuvastatin calcium or Crestor is approved to be used for the following conditions:

• primary hyperlipidemia and mixed dyslipidemia as an adjunct to diet to reduce elevated total-C, LDL-C, ApoB, nonHDL-C, and TG levels and to increase HDL-C
• hypertriglyceridemia as an adjunct to die
• primary dysbetalipoproteinemia (Type III hyperlipoproteinemia) as an adjunct to diet
• homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C, total-C, and Apo
• slowing the progression of atherosclerosis as part of a treatment strategy to lower total-C and LDL-C as an adjunct to die
• pediatric patients 10 to 17 years of age with heterozygous familial hypercholesterolemia (HeFH) to reduce elevated total-C, LDL-C and ApoB after failing an adequate trial of diet therapy
• risk reduction of MI, stroke, and arterial revascularization procedures in patients without clinically evident CHD, but with multiple risk factors
  
  
  Source (Patent)
  Source - Watson
  Source - Crestor 
  
  

Update from PPD - Financial Earnings and other collaborations

Update from PPD - Financial Earnings and other collaborations

• PPD reported a net revenue of 365.4 in the third quarter 2010, an increase of 21 M from the same quarter of last year.  The company's net income in the first 9 months was 76.1 M, a significant decrease of almost 64 M from the same time of last year.  This was primarily attributed to an increase in cost from selling, general and administrative (372 M vs 282.8 M in the first 9 months of 2009).  At the end of September 30, 2010, the company had 613 M in cash, cash equivalents, short-term investments, and long-term auction rate securities.  Source
• PPD announced its collaboration with Bend Research on Oct 26, 2010 to strengthen its position as leader in "drug formulation resource for pharmaceutical companies". Under the collaboration, each company will refer potential business opportunities to the other in certain areas: compound characterization, particle engineering, formulation development, clinical trial material (CTM) manufacturing, analytical development, stability programs and Good Manufacturing Practice release and quality control testing.  The focus of this collaboration will be inhalation formulation development and particle engineering for drug therapies.  Source
• On the same day, PPD announced its new strategic alliance with VirtualScopics Inc, a imaging solution provider based in Rochester, NY in the development of oncology clinical trials.  Utilizing VirtualScopics' advanced software application, PPD hopes to offer its clients seamless, "near real-time, consistent and reliable medical imaging information" to progress clients' drug development programs.  In return, using PPD's strong operational and medical expertise as well as its global presence, VirtualScopics will be able to implement its medical imaging and clinical services to a broader and stronger customer base.  VirtualScopic utilized its proprietary algorithm-based methodology to build its advanced software application that could analyze medical images across different platform such as MRI, PET, CT and ultrasound.  Source

Celtic Therapeutics (formerly Celtic Pharma) has entered an option agreement with Resolvyx Pharmaceuticals

Celtic Therapeutics (formerly Celtic Pharma) has entered an option agreement with Resolvyx Pharmaceuticals in regards to the development of RX-10045 of Resolvyx.  Under the agreement, Celtic Therapeutics will have exclusive option to acquire and license rights to RX-10045 for all eye indications.  In return, Celtic Therapeutics purchased a note convertible to Resolvyx equity.

 RX-10045 is a synthetic resolvin analog.  It’s currently being studied as a topical eye drop product to treat dry eyes.  The compound is set to enter a randomized, placebo-controlled, multi-center phase III trial for the treatment of dry eyes.  The trial is start in 2011. 

Resolvin is a naturally occurring, small molecular mediator.  It protects healthy tissues during inflammatory response occurring within the body when the body is under attack from infection or suffers from injury or other environmental damages.  It can also act to resolve inflammation and promote healing.  Besides RX-10045, Resolvyx is currently developing the oral formulation, RX-1001.

 Source

Vertex reported net loss of 209.0 M in third quarter 2010

Vertex Pharmaceuticals reported  its third quarter 2010 financial earnings with a GAAP net loss of 209.0 million, an increase in net loss of almost 60 million compared to the same quarter of last year. Total revenue was down by 1.2 million compared to the same quarter of last year ( 23.8 M vs 25 M)

Vertex had 1.2 billion in cash, cash equivalents and marketable securities as of September 30, 2010.

Source

New Oral Contraceptive, Lo Loestrin Fe, of Warner Chilcott has been approved

Almost every month, I see some new contraceptive pills entering the market.  This always intrigues me.  Maybe someday I will understand how the market is really behaving. Is the female population on the rise?  Or is it because female tends to delay having a family + children to later days?  Is it the basis for having more contraceptive medications on the market? I don't know.  But it's apparent that this is not going to stop. 

Recently, Beyaz of Pfizer was approved.  Unlike other contraceptive pills, Beyaz contains levomefolate calcium.  The idea behind the pill is to supplement women who are taking contraceptive folate or folic acid.  This they think will prevent the incidence of neural tube defect in newborn whose mother lacks folate in the body during conception. 

Just a few days ago,  the FDA announces the approval of the oral contraceptive by Warner Chilcott, Lo Loestrin Fe. 

Lo Loestrin Fe contains: norethindrone acetate, ethinyl estradiol, and ferrous fumarate. Unlike other contraceptive medications on the market, Lo Loestrin Fe contains only 10 mcg of estrogen which is the lowest dosage of estrogen in any other contraceptive medications. With the approval, Warner Chilcott plans to commercially launch Lo Loestrin Fe in early 2011. Warner Chilcott currently markets Loestrin Fe which contains 20 mcg of ethinyl estradiol.  

I wonder whether this has to do with all the concerns about estrogen and cancer.  Recently, the New York Times reported additional results of the 2002 study (part of the Women' Health Initiative) showed an increase risk of breast cancer in women taking hormone replace therapy (mostly Prempro containing horse derived estrogen and synthetic progesterone).  The effect according to the article is accumulative.

In addition, the National Cancer Institute has also posted some information about oral contraceptives and cancer risks.  The answer though remains inconclusive as to whether the intake of oral contraceptives will increase the risk of various types of cancers.  Even though science is investigating the risk of getting cancer from oral contraceptive, studies have repeatedly shown a decease in risk of ovarian and endometrial cancer in patients using oral contraceptives.  Much of these information remain inconclusive.  Hence, the decision as to whether using hormone therapy or oral contraceptives rely heavily on the patients to make the most informed decision possible.


Just like with any other contraceptive, the boxed warning has been issued:

• Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use.  The risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked.  For this reason, COCs should not be used by women who are over 35 years of age and smoke.

Source - Bayer
Source
Source - Lo Loestrin Fe