Webinar

OMG what a waste of time!!! Are you kidding me!!

 

Record the damn things and make them a weekly lms requirement, but don't waste our time by taking us our if the field in the middle of the day for these freaking programs. The see the value, but not the waste of valuable selling time. Who really has time to find to stop, up ll over to the side of the toad and watch a webinar. Its a flawed design.

 

A little tip about reminding drs to write daw on each prescription, II DOESN'T FUCKING MATTER!!!!!! Both Tivorbex and Zorvolex are unique formulations that are non substitutible anyway, so DAW doesn't mean shit, especially if the RPh is going to screw you over anyway. When you talk to drs like automatons they lose respect for and eventually marginalize anything you say.

 

If the patient balks at the copay then it is switched, end of story.
Whether the pharmacy calls the doctor or not DAW means nothing.

 

My prayer for the week. " lord, please get me out of the dead end, career screwing position as soon as possible"

 

Once again nothing but reminders and just a big waste of time. Folks do you really think this is great information?? What are we learning? If you have nothing to say then don't waste our time. WTF.

 

The FDA mantra over and over. No real science to support it. The lowest effective dose is 7.5 mg of meloxicam. Thanks for the samples and the free lunch. Goodbye.

 

How stupid....it does not make any sense comparing the dosage strength of one NSAID molecule with that of another and saying 7.5 mg is lower.

There is incredible science behind the lower doses and lower adverse events. Observational trials have clearly demonstrated that serious GI, CV and Renal adverse events are dose related. (Agency of Healthcare Research and Quality, AHRQ, a HHS department) recommends the utility of observational trials in comparing harms of various therapies (or dosages of therapies) in their Methodology for Comparative Effectiveness. In fact, the exact relationship between the dose and the serious adverse events have been identified for diclofenac and indomethacin based on the data from these observational studies. Based on that relationship, you have an opportunity to reduce the risk of these serious adverse events significantly with your product.

In addition, observation trials have shown that the immediate release formulations further lower risk of these AEs compared to the delayed release formulations. The quantum of this reduction in risk is being estimated.

These are not just vagaries of data seen in observational trials. There is strong methodological rationale as to why there is this risk reduction with dose and immediate release formulation. NSAIDs work by inhibiting the cyclo-oxygenase enzymes (COX). There are two types: COX-1 that is constitutive (means that they exist in many organs including the stomach, kidney, blood vessels etc>) and COX 2 that is generally generated only when there is an inflammation or injury (on exception is the blood vessels, where COX 2 is constitutive and is instrumental for producing prostacyclin or PGI that performs an important homeostatic role by inhibiting platelet aggregation). COX 1 performs protective functions in the stomach wall, in the renal wall and in the platelets. The COX 1 and COX 2 inhibition that happens with NSAID are dose (plasma drug concentration) related - that is the higher the dose the higher the levels of inhibition of COX 1 and COX 2 enzymes. So at higher doses, more of COX 1 is inhibited and since they protect stomach, kidney and the heart, as more of COX 1 production is inhibited that protection is lost resulting in the adverse events to stomach, kidney and the heart. so you may ask, the same rationale holds for COX 2 also - so if at lower doses COX 2 inhibition will be lower and since COX 2 inhibition is important for efficacy against pain or inflammation, would'nt lower COX 2 inhibition result in lower efficacy. This is the where the science is so elegant - Scientists have looked at the peak therapeutic effects of over 22 different NSAIDs and have shown that noticeable efficacy is seen after 50% COX 2 inhbition and the peak therapeutic efficacy is seen at about 80% of COX 2 inhibition. More than 80% of COX 2 inhibition does not add meaningful increase to the efficacy. This is where the beauty of of a product like Zorvolex comes - PK studies have shown that Diclofenac at 75mg (or 150mg) a day provides about 1300ng/ML of peak drug concentration. To achieve a COX 2 inhibition of 80%, you need only about 78ng/mL peak drug concentration and that should be maintained for about 3-4 hours in a dosing interval to achieve that inhibition. Diclofenac 50mg or 75mg overshoots it with not much efficacy benefit. 80% of COX 1 is inhibited around 800-1000ng/ML. Zorvolex PK studies show the peak drug concentration for the 18mg dose aroung 400ng/ML and 35mg around 600 ng/mL. At these concentrations, you can achieve the 80% COX 2 inhibition and maintain efficacy but lower the COX 1 inhibition.

The above is just the effects of the actual levels of inhibition. Let us discuss the role of formulation when it comes to both the safety and efficacy. Researchers who were examining the reasons for high rates of CV issues with Vioxx found out that when the drug is in the plasma for a longer time, which happens with long half life drugs and delayed release products, they inhibit the COX 2 enzymes in the cell wall of the blood vessels all the time not allowing the COX 2 enzymes to produce prostacyclin or PGI2. PGI2 inhibits platelet aggregation and COX 1 in the platelets promote aggregation. Since PGI2 is not produced, COX 1 allows aggregation to happen without the homeostatic effect of PGI2 and as a result clots form in blood vessels resulting in heart attacks and other CV problems. In addition PGI2 is a vasodilator (meaning expands the blood vessels) while COX 1 is a vasoconstrictor. Again consistent COX 2 inhibition does not allow the production of PGI2 resulting in the vasoconstrictive activities of COX 1 unopposed. This results in lowering of blood flow to the the kidney and the gastric mucosa in the stomach. Lowering of blood flow to kidney increases hypertension (adding to CV risk) and acute renal failure. Lowering of blood flow to gastric mucosa weakens mucosal defense to injury. So it is important not to have constant high drug levels in the plasma for a long time not allowing breaks where COX 2 is not inhibited so they can produce PGI2. Hence the increased serious CV, GI and renal adverse events seen in observational trials with longer half life drugs or delayed release products.

Let us then discuss efficacy - if you dont have constant blood levels, how can you get efficacy for the course of the dosing period. Drug levels in the plasma does not do anything to reduce inflammation or pain. Drugs get absorbed in to the blood after oral administration just so that the blood can transport and distribute the drug to the various tissues and organs. Where the drug is needed is where the pain or inflammation is - the synovial fluid of the knee or hip or back etc. Typically in the pain pathway, especially the nocciceptal one, the role of the COX 2 is to sensitize the area to the other pro-inflammatory mediators such as cytokine, bradykinin etc. that gets released during an injury or inflammation. Once sensitized, the stimuli then is transmitted through the basal horn of the spinal cord to the receptors in the brain causing the person to experience pain. So the faster you inhibit COX 2, the faster you inhibit the sensitization by COX 2 and interrupt the transmission of pain thus improving both the speed and quality of pain relief. So, when you have an NSAID you want to try to get it to the tissues as fast as possible. To get to the tissues fast, you need to get sufficient levels fast in the plasma so it can transfer to the tissues fast. That is exact what the SoluMatrix technology does. Since the molecules are ground in particles that are about 200-400 nm in size, they provide more surface area for absorption and hence achieve rapid blood levels for distrbution to tissues. And since diclofenac has a short half life, it is distributed fast and leaves the blood levels with 4-5 hours allowing atleast 3-4 hours with very minimal drug plasma levels - so the COX 2 enzymes do not have any measurable drug levels in the plasma to inhibit them - so they can go ahead and produce PGI2. Peak levels in the tissue are achieved within a 2-3 hours and the half life of diclofenac in the tissue is more than 2-3 times longer than that of its plasma half life. So the drug remains in the tissue longer where you want it to be and gets out where it should get out. In addition, diclofenac being an acidic NSAID is highly lipiphilic (likes proteins) - and since injured or inflammed tissues have more protein (albumin) than other tissues, diclofenac gets distributed preferentially to just the injured or inflammed tissues - the ones where you want the drug. In contrast, products like naproxen, meloxicam, celecoxib are all non acidic. Means that they get equally distributed to both healthy and inflammed tissues - they inhibit COX enzymes equally in healthy and inflammed tissues.

A lot of this science have been developed since 2005. These different pieces have not really been put together. I think with Zorvolex, you have the most ideal NSAID out there - the best of all the NSAIDs out there. Sure, you dont have all the data yet. Celebrex didnt have any data that they reduced GI bleeds at launch. They had a concept that preferentially inhibiting COX 2 could spare GI AEs. Then after approval and launch, they started building additional data. When my family needs an NSAID, the only one I ill be confident in giving is Zorvolex(r). It provides the best opportuntiy for efficacy and safety based on all the science above.

There are about 4MM patients that take diclofenac every year in the US. Most of them (about 80%) take 150mg daily in delayed release format. At the estimated rates of AEs, for the 4MM people, about 150,000 AEs are likely to happen. You can make a difference to someone's life by taking this seriously and promoting the use of lower doses - this is when all the hardships that you go through in the field, the lunches that you had to carry, the long drives and the long waits - all worthwhile. You will feel genuinely satisfied about doing the right thing and facilitated potentially preventing an injury to happen.

I hope you guys realize that.

 

Wow, I guess you told us. I want to be just like you.

 

It's a very simple question for you - is Zorvolex as effective as generic diclofenac?

You know the answer, we don't know. And you know why Iroko won't do the study? They are too scared that the result would be that Zorvolex is less effective.

So you are asking Dr.'s to believe that a lower dose at cheap price is as good as generic diclofenac with zero evidence and you want us to all believe that the 20% in dose difference creates such an significantly higher cardiovascular risk than generics.

You can site cox-2 inhibition all you want but a head-to-head diclofenac study would answer a big question and your company is deathly afraid to do it.

 

it doesn't matter. What is important is whether Zorvolex improves provides
Pain/symptom relief in acute pain and in OA and the answer is it does and now we have a product that can take care of what the patient comes into see the doctor at lower doses

 

It might not matter to you but it does to our customers. Wouldn't you want to know how it compares to something you've been using effectively for the last 20-30 years? Are you focused on your customers or your bonus check-if you get one?

 

The copay is in the way with Tivorbex. Once the pharmacist offers the generic cheaper, all our hard work goes out the window. Delivery pharmacies maybe an option, but many drs and pts either don't want to be bothered or deal with it. This is not an easy drug to sell, especially considering a modest and not particularly well documented improvement over current options.

 

Marketing directors should be field based and need to spend at least 25% if their time in drs offices so the can speak from experience not from behind a desk. In fact, the industry has changed so much in the last 5 years, even tenured insiders have no clue the BS going on now. Frankly, after one or two more hmo mergers, the hmos are going to direct everything and make our jobs obsolete. They will have so much power in the formulary process, the patients will have to be the primary payers in order for pharma to make any money. Bye bye $0 copay cards.

 

Carve the throat

 

Yo are wrong. This is what shows that you may hear the words your customers say but may not have drawn the right insights. What the customer wants is that when he writes the product does it provide the pain relief required for his patients and does not create any safety issues for him. This experience of the pain relief that his patients have gotten from the generic diclofenac that he had been using is an abstract thing. Its not as if all his patients received the same level of pain relief with generic diclofenac or any other NSAID for that matter. For physicians, efficacy that they see is generally expressed where the patient has not called back saying the product does not work or the next time when he sees that patient the patient says that product is doing well for him. The starting pain levels of the patients are so heterognous so the pain relief perception they have is all abstract and they cannot provide any concrete idea. That's why you could still meet this need of confidence for the physician by pointing out what the starting pain score in the clinical trial and the magnitiude of pain relief acheived. In the post op trial, in 12 hours pain was reduced by 48% and almost 70% by 24 hours where the starting pain score was 74 out of 100 scale. In the OA trial, the WOMAC scores were reduced by about 35 points in 12 weeks - if you care to look at OA trials done with diclo sodium at 150 mg, the magnitude of reduction is very similar to what we saw with Zorvolex and the WOMAC reduction seen with Celebrex and meloxicam were a little lower than what we saw with Zorvolex(r). But essentially the WOMAC reduction seen is typically what you see with NSAIDs. When you put that into perspective to your physicians, that actually answers his need that was expressed by his question. Perceptual studies done with 100s of physicians in our targets have shown that physicians consider the efficacy of Zorvolex to be slightly superior to other NSAIDs. So this is not theoretical. Also, I have personally been with multiple territories across the country and have provided the perspective when such a question is raised. If you cannot understand the deeper insights from your customers, even a head-to- head will not get you success as your customer will give you another question regarding something that you do not have.....

 

You lost. LOSER!!! Go back to Craig's list.

 

i dont know how long you have been with Iroko but the marketing team including the SVP and Executive Director of Zorvolex have spent majority of their time working with reps in the territories since launch and all of 2014. They have also conducted advisory board meetings in various regions and local areas meeting over 500 physicians. They have also been very hands on visiting majority of the managed care organization personnel. They also have systematically collected customer feedback through organized market research in both qualitative and quantitative manner periodically so that they understand the progress of the messages with customers, their questions and what the best way to answer them. The analytics done with the data is one of the best in the industry.

Regarding your comment on the managed care organizations and the mergers, if you had the perspective of following the industry over the past 20 years or so, what you will see is the various stakeholders make strategic moves and neutralize the others advantage. It is really fascinating not only to watch but be a part of the process. That is what is fun. In the early 90s when the PBMs like Medco were beginning to emerge, there was similar cries of the sky falling down. However, what you see is how the various stakeholders like the pharma, physicians, pharmacies all respond to neutralize the others' advantage. What you have stated are signficant strategic moves by the payers. However pls. do not underestimate the role played by pharma. Payers cannot exist without pharma. Despite all these posturing, what the payers want is to use pharmaceuticals to reduce the use of procedures and hospitalizations. You will see Pharma and physcian groups make strategic adjustments. and regarding your jobs, despite all the hue and cry, if you ask most top executives in Pharma, personal selling is the most effective communication media in this industry - none of the others including digital have shown to be anywhere close. So I wouldnt worry. It was just that in the late 90's and early 2000s, excess capacity was added - so when the R&D productivity for pharma in terms of new drugs began to become lean, that excess capacity was shed.

 

The fact that you have to resort to name calling rather than provide rational, lucid arguments shows who the Loser is... Good Bye, Kiddo

 

With all that great marketing knowledge, field rides, and expertise why are the numbers so low? You are getting answers to your questions from doctors who you have paid to sit in meetings for a few hours and hear the message. What do expect them to tell you? I've talked with these doctors and there response is-tell them what they want to hear and maybe some more checks will come my way. Do you honestly believe they are going to be negative about the concept or product if there is money on the table? Come on ladies and gentlemen, don't be so naive.