Monday, January 19, 2009

What is GFR?

Recently, I was presenting to a group that brought up the term GFR. In particular they were stating that the GFR for there plan was at 48% up from 38% the year before. Now for those of you who don't know what GFR is , it simply means Generic Fill Rate.
Now , If this is the case in your Drug Benefit Plan, it should be expected that this % has gone up. Why? Well, here in Canada we have had a few, very large drugs lose patent. When this occurs you see a spike in your GFR. The real question is can your plan sustain it. In the US today , the GFR is approaching 70 % while here in Canada it sits at about 50%.

What is GFR?

Recently, I was presenting to a group that brought up the term GFR . In particular they were stating that the GFR for their plan was at nearly 100%. The plan board thought that GFR was the same as Generic substitution. I really think that their insurance carrier or paid consultant should have explained the difference until I realized that the consultant did not fully understand the terminology difference. So let me explain. Here in Canada most plans have a Generic Substitution policy where once a drug goes off patent then the plan will pay for the less expensive alternative. This is Generic Substitution Rate or GSR. Thus you should currently see Atorvastatin commonly known as Lipitor which is just facing several Generic equivalents have a high GSR. This just occurred in the last week or so, so you may not see it in your current carrier reports but it will impact future reports and should be at 95% +. The GFR rate refers to the number of prescriptions written or filled generically in your plan. In Canada last year the combined average GFR for Public and private plans was at about 54%. In the US that percentage is much higher at over 70% pointing to most prescriptions being written as a generic. Canada is ahead of the US in terms of the number of blockbuster drugs that have gone off patent so we have not done enough to try to take advantage of the lower costs with generics. Much debate is currently going on , as to how we get better pricing on these off patent medications.

Friday, January 16, 2009

From: In the pipeline: Drugs to watch in 2009

For Those of you interested in what to expect in the future , here is an article from Modern Medicine at the following address
We can expect that as these blockbuster drugs come off patent a big shift is going to occur. In Canada we have a group called the Common Drug Review (CDR). A program funded by the FPT Ministries of Health that operates under the aegis of the Canadian Agency for Drugs and Technologies in Health. It reviews and makes recommendations but the provinces are free to make there own decisions. It will be interesting to watch for these new products as they come to market and our Health Care System struggles with the costs.

The article can be found below.

In the pipeline: Drugs to watch in 2009

Jan 20, 2009
Formulary ENews

Several blockbuster drugs will fight to hold onto their top spots in 2009 as new products come before FDA for marketing approval, reported Brian W. Kolling, PharmD, at a recent meeting of the Academy of Managed Care Pharmacy (AMCP) in Kansas City, Mo. Key therapies to watch as they move through the pipeline include medications for cardiovascular (CV) disorders, central nervous system (CNS) disorders, respiratory disease, and diabetes, he said.

According to Keith Bradbury, executive director of drug information at Medco Health Solutions Inc., FDA has delayed approval of many NDAs while the agency struggles with implementing new regulations established by the 2007 FDA Amendment Act (FDAAA).

“We are at a historic time in terms of the number of products the FDA has delayed or allowed the user end-date to pass and extended the review period,” Bradbury said.

For this reason, he said, as many as 62 NDAs could be submitted in 2009. Of these, perhaps 25 will be approved. “There are about 40 to 45 drugs sitting at the FDA today waiting for action,” Bradbury said.

According to Bradbury, a home run might occur in the CV field. Bradbury was referring to rivaroxaban (Bayer/Johnson & Johnson); if approved, this agent will be the first new anticoagulant oral drug to reach the market in more than 40 years, with the potential to replace warfarin.

“This is potentially a multibillion-dollar drug. It looks very promising,” Bradbury said. The benefit of rivaroxaban is the potential elimination of the costly monitoring associated with warfarin.

Another important CV agent in the pipeline is prasugrel (Daiichi Sankyo/Lilly), which, if approved, will compete with clopidogrel. The Cardiovascular and Renal Drugs Advisory Committee is scheduled to meet on February 3 to discuss prasugrel.

“The $64,000 question is: Is the FDA going to be able to tease out from the data whether the drug is in the net beneficial and not harmful? If this happens, then [clopidogrel] is going to have some...competition,” Bradbury said.

Although most of the new drugs expected to hit the market will inevitably carry hefty price tags, the introduction of several key generics should offset some of the medication costs consumers face. “It is our expectation that in 2009, about $11 billion of prescription drugs will be subject to generic competition,” Bradbury said.

The following therapeutic areas are the ones to watch for emerging therapies.

During the next several years, generic products will continue to make inroads into the CV market as the top statin, angiotensin II receptor blocker (ARB), and antiplatelet drug all go off patent by 2012. There is also a full field of factor Xa inhibitors, several of which are now in phase 3 trials.

Statins will still dominate cholesterol management, but combination products and several agents with new mechanisms of action are in development. New products to watch for include GlaxoSmithKline’s darapladib, which targets lipoprotein-associated phospholipase (Lp-PLA2), an enzyme linked to artery-clogging plaque, and Isis and Genzyme’s mipomersen, an apolipoprotein B100 antisense inhibitor designed as a lipid reducer for high-risk CV patients. Two new cholesteryl ester transfer protein (CETP) inhibitors, Merck’s anacetrapib and Roche’s dalcetrapib, are also on the horizon.

There has been a push to develop new antiplatelet and antithrombotic agents to replace less effective and more costly products. As mentioned above, if approved, prasugrel, a platelet inhibitor used for the prevention of CV events in patients with acute coronary syndrome (ACS), could rival clopidogrel, which is set to see its patent expire in 2011. Clinical trials demonstrated that prasugrel may be more effective than clopidogrel in preventing CV death, nonfatal myocardial infarctions (MIs), and strokes, but also that it was more likely to cause serious bleeding. If FDA calls for additional clinical trials to study the bleeding issue, the drug’s approval would be delayed.

SCH-530348 (Schering-Plough), an oral antiplatelet drug, would be the first in a new class of thrombin receptor antagonists. SCH-530348 prevents blood clots by inhibiting the action of thrombin, a key coagulation factor that converts fibrinogen into fibrin. This agent is in phase 2/3 trials.

Another new antiplatelet formulation is ticagrelor, the first reversible oral adenosine diphosphate (ADP) receptor antagonist. Developed to reduce the risk of thrombotic events in ACS patients, ticagrelor inhibits platelet aggregation, which may reduce clot formation. Clinical benefits of reversibility are unclear; however, results of phase 2/3 trials now under way may shed light on the issue.

With limited clinical choices for the prevention of thromboembolic disease, 2 new anticoagulants could meet the need for new products in this area: rivaroxaban, a once-daily direct Xa inhibitor being studied for the prevention of venous blood clots in adult patients undergoing elective hip- or knee-replacement surgery, and dabigatran etexilate (Boehringer Ingelheim), an oral reversible direct thrombin inhibitor being studied for acute venous thromboembolism (VTE) treatment and secondary prevention of VTE, as well as prevention of CV events in ACS.

Dronedarone (Sanofi-Aventis), a multichannel blocker with antiadrenergic properties that is chemically similar to amiodarone, is being studied in patients with atrial fibrillation or atrial flutter. Clinical trial results indicate that this agent may be better tolerated than amiodarone.

Central nervous system
Researchers are aggressively working to develop new products that will eliminate some of the undesirable side effects associated with many currently available CNS drugs. Several new migraine treatments are under investigation, as are new fibromyalgia agents. The CNS market will also see several top drugs going off patent in 2010 and 2011.

Existing antidepressants often have negative side effects, efficacy problems, and poor patient compliance. One new drug in the pipeline is saredutant (Sanofi-Aventis), a neurokinin-2 receptor antagonist with a mechanism of action different from any employed by existing drugs. It blocks the effects of neurokinin-2, thereby preventing the neurochemical changes induced by stressful conditions in various brain regions.

Melatonin receptor agonists are also in the pipeline, with one of the lead compounds, agomelatine (Novartis), now in phase 3 trials. Compared with existing antidepressants, agomelatine is the first melatonergic agent to demonstrate favorable results in its effect on sleep, weight, and sexual function.

Although antipsychotic drugs are the mainstay of schizophrenia treatment, common side effects such as metabolic disturbances, sexual dysfunction, hyperprolactinemia, and cardiotoxicity lead to poor long-term adherence. As a result, researchers are working to develop a third generation of antipsychotics that may provide broader efficacy, reduced side effects, and improved tolerability. Several NDAs have been submitted, among them applications for sertindole (Lundbeck), which is associated with less sedation when used to treat schizophrenia, and asenapine (Schering-Plough), a new 5-HT2A/D2 receptor antagonist for treatment of schizophrenia and bipolar mania disorder. FDA issued a complete response letter for asenapine earlier this month; the letter asked for supplemental data but not for additional clinical trials.

Two migraine treatments are in late-stage development: telcagepant (Merck), an oral calcitonin gene-related peptide (CGRP) receptor antagonist, and botulinum toxin A (Botox; Allergan), which is injected every 12 weeks in trials. Both agents are in phase 3 trials, and the manufacturers hope to file for FDA approval in 2009.

Milnacipran (Savella, Forest/Cypress), a selective norepinephrine serotonin reuptake inhibitor (NSRI), was approved earlier this month for the management of fibromyalgia. [S,S]-reboxetine (Pfizer), a norepinephrine reuptake inhibitor, is also in development for this indication. Reboxetine is in phase 3 clinical trials.

The sleep-disorder market may see the arrival of 2 new insomnia drugs: doxepin (Somaxon) and eplivanserin (Sanofi-Aventis). Unlike existing sleep aids, doxepin selectively blocks the neurotransmitter histamine and may improve insomnia symptoms without serious adverse effects. The PDUFA date for the doxepin NDA was recently extended to February 29, 2009. Eplivanserin, a selective 5HT2A receptor antagonist, is in phase 3 trials. Zolpidem tartrate extended release (Ambien CR; Sanofi-Aventis) is scheduled to go off patent in March 2009.

Respiratory agents
Respiratory drug development is focused on a wide range of potential combination therapies. A new class of drugs is not likely to be available for at least 3 to 5 years.

Novartis is developing indacaterol, an ultra-long-acting beta agonist inhaler, for the treatment of chronic obstructive pulmonary disease (COPD) and asthma. An NDA for aclidinium bromide (Forest/Almirall), an inhaled muscarinic antagonist for COPD, is expected to be filed in the fourth quarter of 2009 or the first quarter of 2010.

Tadalafil (Cialis, Lilly) has demonstrated promising results for the treatment of pulmonary hypertension. An NDA for inhaled treprostinil (United Therapeutics) for the treatment of pulmonary arterial hypertension was submitted in June 2008. Pfizer is awaiting FDA approval for sitaxsentan, an endothelin receptor antagonist for pulmonary arterial hypertension treatment.

Diabetes treatments
Few patients with diabetes achieve their target goals for blood glucose, cholesterol, and blood pressure, and many of these patients are undertreated. Drugs are being developed to meet the needs of this population as the incidence of diabetes assumes epidemic proportions.

Two new dipeptidyl peptidase (DPP-4) products, alogliptin (Takeda) and saxagliptin (Bristol-Myers Squibb/AstraZeneca), have demonstrated favorable results in patients not adequately controlled with existing insulin products. Alogliptin is pending FDA approval; the PDUFA date for this NDA was recently extended to June 26, 2009. An NDA was submitted for saxagliptin on June 30, 2008.

Novo Nordisk’s liraglutide, a GLP-1 analog, has demonstrated a risk of hypoglycemia much lower than that connected with many existing drugs. In phase 3 trials, more than half of the participating patients achieved a glycosylated hemoglobin A1c (HbA1c) of <7%. A benefit that liraglutide shares with other GLP-1 analogs is its potential to significantly reduce weight. An NDA was filed for liraglutide on May 23, 2008; the Endocrinologic and Metabolic Drugs Advisory Committee is scheduled to discuss this agent on April 2 or 3.

Dapagliflozin (Bristol-Myers Squibb/Astra-Zeneca), a highly selective inhibitor of sodium glucose cotransporter 2 (SGLT2), has a dose-dependent effect on HbA1c levels and fasting plasma glucose (FPG). In clinical trials, the drug produced slight weight loss but was also associated with a higher incidence of urinary tract infections.

In a field of failed attempts to market inhaled insulin, MannKind is hoping to gain approval for a delivery system that administers a dry-powder insulin formulation through a palm-sized inhaler. Phase 3 trial data comparing this powder formulation with injected insulin have demonstrated similar efficacy between the 2 formulations.
CMA President Seeking Health Care Answers

OTTAWA, Jan. 15 /CNW Telbec/ - Dr. Robert Ouellet, President the Canadian
Medical Association (CMA), will begin the second stage of his European health
care fact-finding mission on January 19.
"The goal of this project is to suggest compatible and efficient measures
that could improve access to our own health system and address lengthy wait
times," said Dr. Ouellet. "The current economic climate demands that we look
for ways to increase efficiency and provide value for money in health care
service delivery. There could be no better time to suggest to Canadians a
positive transformation of the health care system."
Dr. Ouellet's research will focus on finding concrete examples of how
certain measures were implemented and have contributed to improving the health
care system of various European countries. By drawing on the experience of
European countries that have been top performers in terms of value for money
and access to heath care, we can address the problems afflicting Canada's
health system.
Dr. Ouellet and CMA representatives will be meeting with key individuals
who have played a major role in improving their country's healthcare system
and will witness firsthand how certain programs or projects have been
implemented. The team will visit Denmark, Belgium, the Netherlands and France.
Stage 1 of this mission began in November 2007 with a visit to the United
"It's important that we look at the practices of countries that rank at
the top in terms of comparative international health policy studies. We're
going without any preconceived ideas, and we're keeping an open mind about all
types of practices," Dr. Ouellet stresses. "The first stage of the tour, to
the UK, revealed several interesting models. I'm looking forward to the second

A series of regional and national consultations with the Canadian public
will follow the first draft of the report of this study mission. The final
report should be made public in June 2009.

For further information: Lucie Boileau, Media Relations Manager, 800
663-7336, (613) 731-8610 ext. 1266
Here is a story from the CMA about Dr.H. Visser and how he uses EMR's.

Post #2 Government of Canada Works to Improve Knowledge About the Safety and Effectiveness of Drugs

From the Health Canada site:    Part of the discussions at the Conference in Boston centered around this issue.  The presentation from the FDA certainly made it clear that it is a global concern and that because of todays global outsourcing by both Brand and Generic companies , it is imperative that more controls are needed. 
Government of Canada Works to Improve Knowledge About the Safety and Effectiveness of Drugs

Thursday, January 15, 2009

First Post Jan 15, 2009

I read a really interesting Blog this morning by Dr. Fein of Drug Channels ( .  The US has exactly the same concerns  as we do here in Canada.  It appears from the Third Party Plan description that they are feeling the pinch.  
Take a look.