Financial updates: Furiex, Wex Pharma, NovaBay

Here comes a string of losses... financial update

• Furiex Pharmaceuticals
•  Furiex reported a net loss of 21.18 M in its third quarter of 2010, a big increase from a net loss of 5.7 from the same quarter of last year.  
• The main contributor to this net loss is coming from Research and Development Expense.  An increase of over 19.5 M compared to the same quarter of last year.
• The company had a total revenue of 288,000  a decrease of almost 160,000 compared to the same quarter of last year.
• The company total asset added up to 142 M at the end of September 30, 2010.  An almost 90 M increase from the end of December in 2009.  
• Furiex is a spin-off from PPD, a premier contract research organization which is based in Wilmington, NC. 
• Press Release Furiex
• WEX
• Wex Pharmaceuticals is a member of CK Life Sciences Group.
• On Nov 12, 2010, WEX Pharmaceutical announced a net loss of 2.37 M at the end of its third quarter which ended on Sept 30, 2010.  This was an increase of 0.33 M in net loss compared to the same quarter of last year. 
• From the beginning of its fiscal year, WEX has accumulated a net loss of 5.34 M, a decrease of 1.3 M compared to the same period of 2009.  
• As of Sept 30, 2010, the company had 19.38 M in cash and short-term investment.  This was an increase of 14M from 5.2 M at the end of Dec 31, 2009.
• WEX Pharma
• Novabay
• Novabay of  Emeryville, CA reported a net loss of 1.6 M in the third quarter of 2010, an increase of 1.5 M from the same quarter of last year. 
• The company earned 2.1 M from license and collaboration revenue in its third quarter of 2010, a decrease of 1.1 M compared to the same quarter of last year.
• NovaBay has a collaboration agreement with Alcon for the development of NovaBay's Aganocide compounds which are being investigated for the treatment of eye, ear and sinus infections (+ contact lenses care)
• In addition, NovaBay and Galderna have partnered to develop Aganocide compounds for major dermatological conditions.
• So what is Aganocide: aganocides are compounds that mimic human's natural defense system which is often employed to fight bacterial and viral as well as other infections.  According to the company website, these compounds are : fasting acting, broad in spectrum of activity, effective against multi-drug resistant bacteria, effective against biofilm and have good safety profiles.
• The company had 10.8 M cash, cash equivalents and short-term investments as of Sept 30, 2010.  this was a decrease of 0.5 M from the same quarter of last year.
• Press Release

Egrifta is approved for the treatment of the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy

Egfrita or tesamorelin of Theratechnologies has been approved for the treatment of the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy.


About Lipodystrophy in HIV-Infected patients:

This will be the first and only treatment for the above indication. Patients with HIV often are put into a combination of medications.  Often time, one of the component of their combination therapies is a class of drugs called protease inhibitor.  As a class, it has been shown to induce abnormal fat distribution (facial and peripheral wasting, buffalo hump and central obesity).  Protease inhibitors could also cause dyslipidemia (increase in lipid concentration in the blood).  As a result, when given long term, patients are often prescribed medications to control their serum lipid. 

About Tesamoreline:

Tesamorelin is a synthetic analogue (peptide) of the human growth hormone releasing factor (GFR) developed by TheraTechnologies. GFR activates pituitary cells in the brain to increase the synthesis and release of endogenous growth hormone. 

• Comment from me: A bit of a concern as to how this drug works.  Increase the human growth hormone releasing factor could affect metabolism in the body.  Although not a definitive, it could potentially increase cellular production.  As indicated in the press release, patients with known history of malignancies should not be treated with EGRIFTA. Besides this, patients who were treated with EGRIFTA had significant increase in the level of HbA1c.  HbA1c is a marker that physicians/practitioners often use to monitor patients' blood glucose conditions over past 3 months. Hence, patients need to monitor glucose level closely to prevent the development of diabetes. In diabetes patients, using EGRIFTA should be accompanied by frequent blood glucose monitoring to prevent the worsening of current conditions.  For other information, please refer to package insert.

Agreement + Marketing:

In 2008, Theratechnology signed a collaboration and licensing agreement with EMD Sereno, an affiliate of Merck.  Under the agreement, EMD Serono will have exclusive commercialization rights to EGRIFTA (tesamorelin for injection - side note: I don't know who designs the drug name, but this definitely stands out as one of the harder one to type...).  Upon approval, Theretechnology will receive $25 M USD as milestone payment.

Additional Required Information:

•  Upon approval, Theratechnology is required to performed three post-marketing requirements: 
• A long-term observational safety study for tesamorelin acetate
• a single vial formulation
• additional trial to assess whether EGRIFTA could affect diabetic retinopathy in diabetic HIV-infected patients with lipodystrophy and excess abdominal fat

Supply and Dosing

•  The package Insert recommended giving 2 mg of EGRIFTA subcutaneously once a day at the abdomen.  Sites should be rotated daily.
• EGRIFTA is currently available in 1 mg vial.  It comes with a vial of sterile water for injection which is used for power reconstitution.
• Comments from me: This explains why the FDA requires that Theratechnology reformulates the medication into a single vial.  If the required dose is 2 mg, patients will have to reconstitute two vials in order to meet the dosage requirement.

Adverse Events:

• Most commonly reported adverse reaction: arthralgia, erythema at injection site, pruritis, pain in the extremity, peripheral edema and myalgia.

• Other concern:  it's metabolized by P450 enzyme.   Hence, drug interactions need to be monitored closely.
• Avoid use in patients who are nursing
• It's contraindicated in pregnancy: Category X
• Comment from me: Many HIV medications are metabolized by P450.  The package insert indicated that a pharmacokinetic study in healthy subjects showed a decrease in concentration of ritonavir (a common HIV component of the combination therapy).  No viral load information is provided although the trials could have used the blood serum for these information.  If patients were to use EGRIFTA, viral load should be monitored closely due to a potential decrease of drug concentration.  In addition, this could potentially put patients at risk for other opportunistic infections.

Clinical Data

EGRIFTA was approved based on data from the two multi-center, randomized, double-blind, placebo-controlled phase 3 studies.  The first phase III trial consisted of a 26-week main phase and the second phase III trial was the 26-week extension.  EGRIFTA was tested in 816 HIV-infected patients having excess abdominal fat associated with lipodystrophy in these two phase III trials.

• The primary endpoint for the main phase was: the percent change in  visceral adipose tissue (VAT) from baseline.  The assessment was made using computed tomography scan at the L4-L5 vertebral level.
• Interesting study design which I think can make it hard to interpret
• Main phase: 1:1 randomization into either placebo group or EGRIFTA group
• Extension phase: patients who were treated with placebo were switched to EGRIFTA.  Patients who took EGRIFTA were re-randomized into either the placebo group or EGRIFTA group.
• Results
• Main phase:
• Significant reduction in VAT from baseline in EGRIFTA group was observed.  The least-square mean reduction from baseline was 27 cm2.  Patients in the placebo group gained an average of 4 cm2.  The difference in change between the two group was presented in 95% confidence interval with a range of -39 cm2 to 24 cm2.
• The percentage change of VAT from baseline was significantly higher in the EGRIFTA group compared to placebo.   The least-square mean reduction from baseline of the EGFRITA group was 18% reduction and the least-square mean increase from baseline of the placebo group was 2% increase. (95% CI : -24%, -15%)
• Extension phase:
•  Patients in the EGRIFTA group experienced a 14% of VAT while patients in the placebo group experienced a 2% decrease of VAT.  This difference was significantly (95%: -16%, 7%).
• For further information please refer to company information.

Press Release
Package Insert

October Drug Approvals Update

October Drug Approval has been update!

November list is coming!

Clinical Trial Updates: TB Alliance (PA-824) and Nabi Biopharmaceuticals (NicVAX)

• PA-824 of TB Alliance, a non-profit organization, moves into the phase II clinical trial (NC001) which uses PA-824 in combination with moxiflocaxin and pyrazinamide for the treatment of Tuberculosis.  The trial intends to study the effectiveness, safety and tolerability of the drug combination listed above after 2 week treatment and three months of follow-up.  The trial will enroll 68 patients at two centers in South Africa.
• The study is financially supported by the US Agency for International Development, the Bill & Melinda Gates Foundation, and the UK's Department of International Development
• Press Release - TB Alliance 

  **************************************

• Nabi Biopharmaceutical has successfully completed enrollment for its phase III trial using NicVAX(R), Nicotine Conjugate Vaccine) for the treatment of Nicotine Addiction and Prevention of Smoking Relapse.
• The trial was initiated in March 2010.  Final data are expected in early 2012.
• Regulation:
• The study was approved under the Special Protocol Assessment or SPA.  The European Medicines Agency has reviewed and provided scientific advice to Nabi Pharmaceuticals on the trial protocol. 
• Agreement:
• In March 2010, GSK Biologicals and Nabi signed an exclusive worldwide option and license agreement under which GSK biologicals will have rights for the development and commercialization of NicVAX.  Upon signing the agreement, GSK Biologicals SA paid Nabi Pharmaceuticals a nonrefundable $40 M upfront payment.  Other financial terms are also included. 
• About NicVAX(R)
• When a person smokes, nicotine which is a small molecule can travel to the brain and stimulate the secretion of stimulant which causes pleasure and addiction.
• NicVax is a vaccine that works to stimulate antibody (a molecule that can bind to nicotine) to nicotine.  The antibody-nicotine complex as a result will not be able to cross the blood brain barrier as easily as the simple nicotine molecule.  With this, the company hopes that the decrease access of nicotine to the brain will result in a decrease in fewer stimulant secretion.  Hence, a decrease in pleasure and addictive-effect of nicotine will be diminished.  
• What makes NicVax different from other therapy: the company hopes with the circulating antibodies, patients will be able to maintain abstinence longer than what other current therapy offer.
• Study Specific:
• Approximately 1000 patients are enrolled in the trials.  
• The study primary endpoint: long-term abstinence from smoking at 12 months.
• Secondary endpoints: abstinence rate at various time intervals, safety and immunogenicity, and the effect of NicVAX on withdrawal symptoms, cigarette consumption, smoking satisfaction and nicotine dependency.
• Related Study(ies)
• This is the second of the two required phase III clinical trials.  The first phase III trial has completed its patient enrollments in July 2010 and final data are expected in the fourth quarter 2011.
• Comment: in theory, it might be good if it works.  I would pay attention to adverse reactions that patients might experience.  The press release did not indicate common adverse events in previous trials (which I think should be included).  Withdrawal symptom is also a big factor in how well patients can tolerate the treatment.  I supposed, the antibody is developed, it will stay there.  This might prevent future relapse.  So the company might be even considering a long term trial to see if this is really the case.
• Press Release - Nabi

The FDA approved Kombiglyze XR of AstraZeneca and Bristol-Myers Squibb

The FDA has approved a new fixed-dose combination anti-diabetic drug , Kombiglyze XR, of Bristol-Myers Squibb and AstraZeneca.


In 2007, BMS and AstraZeneca entered into a collaboration to research, develop and commercialize selective investigational products for the treatment of type 2 diabetes. It will be manufactured by BMS and marketed by both BMS and AstraZeneca.


Kombiglyze XR is a fixed-dose combination of saxagliptin and metformin HCl extended release.  Kombiglyze XR tablets are available in 3 different strengths.

• 5 mg of saxagliptin and 500 mg of metformin HCl ER
• 2.5 mg of saxagliptin and 1000 mg of metformin HCl ER
• 5 mg of saxagliptin and 1000 mg of metformin HCl ER

 

Indication:

Kombiglyze XR is indicated for the treatment of type 2 diabetes in adults in addition to diet and exercise.

Clinical studies:

Kombiglyze XR is approved based on the following:

• A multicenter, randomized, double-blind, active-controlled, 24-week study enrolled 1,306 patients whose baseline A1C levels were 9.4%.  In this study, patients were treated with either placebo + metformin IR tablet or saxagliptin + metformin IR as separate tablets.  
• According to the package insert, Kombiglyze XR tablet has not been used in clinical study.  But bioequivalence between Kombiglyze and its counter part (saxaliptin and metformin XR administered separately) has been conducted.  However, in the two clinical trials that lead to the approval of Kombiglyze XR, metformin IR was used in place of metformin XR.  And no bioequivalence study has been conducted between Kombiglyze XR and combination of saxagliptin and metformin IR.

• According to the result of the 24-week trial: patients taking combination of saxagliptin 5 mg and metformin 1000 mg IR showed a significant reduction in A1C level when compared to placebo + metformin 1000 mg IR ( -2.5% vs 2.0%).
• In addition, the study also reported significant reductions in fasting blood glucose and post-prandial blood glucose were observed in the saxagliptin and metformin IR group when they were compared to the metformin IR and placebo combination.

• Another 24-week, randomized, double-blind, placebo-controlled study enrolled 743 type 2 diabetes patients whose baseline A1C levels were 8.1%.  In this study, saxagliptin and metformin IR were used in combination as separate tablet.  This combination was compared against metformin monotherapy. 
• The result showed significant reduction in A1C level in the combination therapy group compared to metformin monotherapy (-0.7% vs +0.1%; 5 mg saxagliptin + metformin IR vs metformin IR + placebo respectively).
• A significant reduction in A1C level in 2.5 mg saxagliptin + metformin IR compared to metformin IR + placebo was also observed (-0.6% vs 0.1%)
• Combination therapy also had significantly reduced fasting blood glucose and post-prandial blood glucose compared to metformin IR + placebo group.
• Incidences of hypoglycemia (low blood sugar) were as followed: 5.8%, 7.8% and 5.% for 5 mg saxagliptin combination therapy, 2.5 saxagliptin combination therapy and metformin IR monotherapy respectively.

How they work: 

• Metformin HCl is a biguanide and has long been used as the first line treatment for patients with type 2 diabetes.   Its brand name is Glucophage.  It works by increasing insulin sensitivity and decreasing glucose absorption as well as hepatic glucose production.

• Saxagliptin is dipeptidyl Peptidase IV (DPP-IV) inhibitor.  DPP-IV is an enzyme that degrades a hormone called incretin.  Incretin is a glucagon-like peptide and glucose-dependent insulinotropic polypeptide (GIP).  The presence of incretin will increase insulin synthesis and secretion from the pancreas.  At the same time, it also decreases glucagon secretion from the pancreas.  As a result, incretin is important in glucose homeostasis.  In diabetics, glucose sugar usually runs high. Hence, by inhibiting the degradation of incretin to prolong its effect in glucose homeostasis, a decrease in blood sugar is observed.  

Saxagliptin is not the only DPP-IV inhibitor on the market.  Sitagliptin is another DPP-IV inhibitor.  In addition, sitagliptin is available in fixed-dose combination with metformin.  The brand name for this combination is Janumet.

Safety information:

• Most common adverse reaction in naive-patients treated with  5mg of saxagliptin and 1000 mg metformin XL are: diarrhea (6.9%), headache (7.5%) and nasopharyingitis (6.9%)

Boxed Warning:

• Patients taking Kombiglyze XR should be aware of the risk of having lactic acidosis due to accumulation of metformin in the body.  The risk is higher in patients having sepsis, dehydration, excess alcohol intake, hepatic impairment, renal impairment, and acute congestive heart failure
• For additional information, please refer to Kombiglyze XR Package Insert

Please refer to package insert for more information and consult physician before taking new medication.  The information provided here is not meant to offer medical advices or consultations.

Source - Press Release

Update: Pfizer with tasocitinib and Valeant Earnings

The phase III trial using tasocitinib as monotherapy for the treatment of moderately to severe rheumatoid arthritis against placebo showed a significant improvement in ACR20 response rate and mean change in the HAQ-DI scores from baseline compared to placebo group.  The study did not meet its third primary endpoint which was the rate of DAS28-4 (ESR) < 2.6. 

•  Tasocitinib or CP-690,550 is an investigational novel, oral JAK inhibitor.  It inhibits an enzyme called JAK which is involved in the production pro-inflammatory cytokines in the inflammatory pathway.
• ACR20 is a scale developed by American College of Rheumatology. 
• HAQ-DI is health Assessment Questionnaire Disability Index
• DAS is Disease Activity Score
• Source - Press Release

Valeant reported a net loss of 207.9 M in its third quarter of 2010 ended on September 30, 2010.  This is a significant decrease from a net income of 40.4 M compared to the same quarter of last year. 

• The company had 11.1 B in assets an increase of 9B when compared to the end of 2009.
• Source - Press Release 

Update from: Watson (earning & agreement), Savient (earning & Krystexxa launch), cadence ( earning)

Cadence pharmaceutical announced a net loss of 11.7M, an increase of 0.3 M compared to the same quarter of last year.  

• Ofirmev (intravenous formulation of acetaminophen) of Cadence pharmaceutical has been recently approved by the US FDA.
• Compared to the same quarter of last year, the company spent 0.9 M less in research and development (3.5M in 2010 vs 4.46 M in 2009) due to the discontinuation of the development of omiganan pentahydrochloride.
• As of September 30, 2010, the company had 59.7 M in cash, cash equivalents and short-term investments.
• Source - Press Release

Watson pharmaceutical announced a net income of 105.9 M in its third quarter of 2010, an increase if 15.9 M in the same quarter of last year

• The company had 882.4 M in revenue, a 220M increase from the same quarter of last year.
• Watson is one of the leading pharmaceutical companies in developing and distributing generic pharmaceuticals products and specialized branded pharmaceuticals products on Urology and Women’s Health
• As of September 30, 2010, the company had 265.9 M in cash and marketable securities.
• In addition, on November 2, 2010, Watson has signed an exclusive agreement with Ortho-McNeil-Janssen Pharmaceuticals to market the generic version of Concerta (R) or methylphenidate hydrochloride extended release.  Under the agreement, Watson will begin commercial launched of its authorized generic of Concerta on May 1, 2011 in the US.  OMJPI will receive share of the net sales from Watson’s authorized generic Concerta.  Concerta (R) or methylphenidate is approved for the treatment of attention deficit hyperactivity disorder.  The agreement will be valid until the end of 2014.
• Source - Press Release - Financial Earning
• Source - Press Release - Agreement

Savient pharmaceuticals announced a net loss of 59.4 M in the third quarter of 2010, an increase in 45.5 M in net loss compared to the same quarter of last year.  

• On the same day, Savient announced that it will ship its newly approved product Krystexxa to specialty distributors starting Nov 30, 2010.  Krystexxa was recently approved by the US FDA for the treatment of chronic group in adult patients refractory to conventional therapy.  
• Krystexxa or pegloticase ss a PEgylated uric acid specific enzyme.
• Pegloticase works by catalyzing the oxidation of uric acid to allantoin.  This leads to the reduction in serum uric acid.
• As of September 30, 2010, the company had 75.7 M in cash and short-term investment
•  Source - Press Release