Expensive targeted therapies are on the rise. Does cost ever play a role drug treatment? I think we are going to have to deal with this soon.

As the pharma and biotech industry moves towards more targeted therapies, cost of treatment increase dramatically. The latest cancer drugs are targeted to specific DNA sequeneces and mutations and their costs can be over $100,000 per course of treatment. They also might only extend life for a few months. However, expensive and targeted treatments have given some patients years.

Avastin, which lost its approval for breast cancer, is one of those extremely expensive treatments. Patients and even oncologists do not like losing treatments even if they do not seem to work all of the time or even predictively. Patients on Avastin were horrified to lose the drug's approval and it was heart-wrenching to read their stories.

But does cost play a role in the delivery of US drug treatments? It does in other countries.

Does stronger efficacy and more precise patient stratification make very expensive drug use more defensible? Targeted therapies are supposed to be just that, targeted to a particular marker and theoretically they don't work as well or at all in the absence of that marker. But patients report being on Herceptin who do not have HER2+ breast cancer. And we see that there are lung cancer patients on Tarceva who do not have have the EGFR mutation. Sometimes after patients fail on other treatments, we do see the use of targeted therapies in untargeted ways. Should they be if there is no evidence that they would work?

Unfortunately Avastin lost its approval because it was considered to be ineffective and Genentech could not explain why the 17,500 women who found the drug valuable were different. Why does Avastin work for some patients and not for others? If the brand knew that then I think the FDA would have allow the drug to keep its approval for the right patient and people would have been less likely to call out the death panels.

Development of more targeted drugs is a trend on the rise. So astronomical cost for treatment will be on the rise as well. Do we demand more patient stratificatoin and then make everyone stick to it? What is fair to the patient and what is fair for everyone else?

I think we are all going to have to really deal with these issues in the very near future.

Does Facebook matter for pharma companies the way they think it does?

Over the last few weeks, pharma companies and those who follow pharma have been talking about Facebook not allowing pharma to continue to block comments on their pages. I have been confused by all of the fuss this causes.

Wool Labs has been studying patient and physician experiences and behavior online for a few years now. In the hundreds of studies we have performed, Facebook has never been one of the top 200+ sites that houses or shares influential content for patients or physicians. Never. What we mean by influential content is content that patients and/or physicians read, discuss, comment on, share with others, use to make decisions, and change behavior.

So as far as we can see (as we see very far indeed), Facebook pages do not host deep, involved, well-read, or heavily discussed content consumed by patients and/or physicians who suffer from or follow a particular disease/condition or use/prescribe a particular treatment.

Now, of course pharma-sponsored sites don't allow comments so that explains why their sites don't show up in our studies. But presumably a patient who is discussing his/her condition would allow comments and invite others to share similar stories. And we see those but they are not drawing the thousands or tens of thousands of patients that others sites draw. And those non-Facebook sites are what need to matter to pharma.

Patients and physicians share their experiences all across the Internet from well organized disease-specific communities to personal blogs to seemingly unrelated non-health sites.

So while I think it is sad to see some pharma companies pulling Facebook pages, as I always want to see pharma involved with their customers. I would also like to see pharma put as much effort into studying the rest of the Internet as I have seen them put into Facebook.

It is the rest of the Internet that is screaming for pharma to pay attention. It is the rest of the Internet where pharma can learn what their patients and physician believe and how they choose their actions. It is the rest of the Internet that influences and therefore, matters more.

Another Actos Prediction Comes True & Lawsuits Begin

Back in February of this year we studied the oral diabetes drug, Actos. We had previously studied Avandia and found the starter back in 2004 for the lawsuits that eventually happened in 2008. A friend asked me why Avandia became so damaged while Actos seemed to escape the same fate even though we found that Actos had many concerns from cardiac problems to cancer risks. But the one thing that seemed to not haunt Actos was reported deaths attributed to Actos the way that deaths were attributed to Avandia.

That seems to have changed to today. We predicted that if patients and caregivers started to attribute deaths directly to Actos, that lawsuits would happen almost immediately. Avandia lawsuits took years to happen but the legal community has been looking for an Actos weakness for years. And we predicted that once they found it, the lawsuits would follow fast, furious and in large numbers.

The cancer risk problem that had Actos to be removed from the market in Germany and France in June and caused the FDA to increase warnings, is causing deaths from bladder cancer. Patients and caregivers are directly attributing fatal cancers and death to Actos.

One law firm is reporting that they represent 120 clients and every day that they will add 30 or more a week. Dozens of other firms are advertising for clients.

We see this development as the beginning of the end for Actos. Their combination product of Actos + alogliptin should be at risk as should the use of Actos for other indications such as multiple sclerosis.

If we deepen our prediction as lawsuits begin, we believe that Actos will lose FDA approval by end of the year. And the last TZD falls.

Diabetes Medication and Weight Gain

As we continue to study various diabetes medications and patient experiences, I am struck by the number of oral medications that cause weight gain. Patients reported weight gain with 12 of the 18 drugs we studied. And 6 drugs had weight gain incidences of 12.9% (Amaryl) to 31.5% (Actoplus Met). This means that of all of the reports of side effects, weight gain reports comprised 31.5% for Actoplus Met, for example.

Many type 2 patients are trying to lose weight. So the fact that their medication makes that close to impossible and actually has them gaining what could be significant amounts of weight is unacceptable to them.

However, many physicians seem to dismiss patient complaints of weight gain. And today I read an article that sparked this post. I was reviewing information about Takeda releasing new data this week to the FDA on their DPP IV inhibitor, alogliptin. Alogliptin and Actos+alogliptin were originally rejected by FDA because Takeda did not have enough cardiovascular safety data. Takeda is running more studies to specifically look at cardio issues, which is a good thing.

In my research, I found an article from 2010 where researchers favorable to the Actos+alogliptin combo stated that the greater the increase in weight a patient experienced, the greater the decrease in HbA1c. He therefore concluded that the weight gain was purely cosmetic and not a metabolic issue. This was a peer-reviewed article on the NIH website published in Vascular Health Risk Management. In our study, Actos had an incidence of weight gain of 22.5% with some patients report as gaining as much as 50-60 pounds in a manner of a few months.

Significant weight gain has to further stress the already stressed system of a patient with diabetes. More weight has to be a bigger problem that simply cosmetic.

So not only are patients faced with physicians who do not disclose the weigh gain potential of their medications but those evaluating new drugs may not take this side effect seriously. There are several studies that show that even a 5-10% reduction in weight, say 10 to 20 pounds in someone who weight 200, reduces blood glucose levels and reduces the need for medications.

Patients find weight gain caused by diabetes medication to be important and want physicians and researchers to feel the same way.

AZ & BMS's new diabetes drug, dapagliflozin, not approved by FDA

Two weeks ago, I wrote about AZ & BMS's new diabetes drug, dapaglifizon. Looking at the data, I had my concerns about the drug and its links to cancer, increased infections, and increased renal stress and liver stress.

The drug had it review on July 19. By 9 to 6 votes, the panel rejected the drug over liver and cancer concerns. This was to be the first drug in this new class of SGLT2 inhibitors that removes glucose by moving it through the kidneys and then through urine.

It will be interesting to see what happens with similar drugs from Lilly, J&J, Astellas and Boehringer Ingelheim. Will they have time to ensure they have different data? Can they have different data?

I have to say I was not excited about this new class when I first read about it. I understand it would be once a day dosing and doesn't seem to impede weight loss - these are big positive for patients especially the weight loss.

But the risks of some of the newest classes of drugs are high. And we have just begun to see problems with DPP IV's which I predict will increase.

The FDA may send dapagliflozin back for more trials. But for me, efficacy would have to be tremendous and physicians would have to really screen who gets the drug, for the risks to be worth it.

Proactive Product Safety and Efficacy Surveillance Through Observational Research

I just read an article in PharmaVoice on the value of proactive pharmacoviligance . It was dated February 2011; I'm a bit behind on my reading.

However, I couldn't agree more. Manufacturers need to study their products closely post commercialization in order to understand how those products perform once they are used outside of the clinical setting. It is unrealistic to assume that patients and physicians will always have the exact same experiences observed in clinical trials. The world outside of the clinical trial is filled with comordities, concomitant medication, variable adherence, and more. Post-marketing surveillance studies can also serve as a way to catch concerns and address them before they become real issues like lawsuits and loss of approval.

Manufacturers should also want to preserve their products for potential future indications and to ensure that the right patients get the right treatment. I expect executives to would want to know how physician and patient experiences are going to impact the company's bottom line.

Let's face it, all safety and efficacy issues bubble to the surface eventually. We assume that executives would want to proactively manage their portfolios not just because it is good patient care, but because it is good business too.

We spend a good deal of time analyzing patient and physician experiences with pharmaceutical products. We get a real look at how patients and physicians use drugs and devices in real-world settings. We see safety and efficacy issues that definitely can pose potential problems for brands and for companies. We see misunderstandings that offer companies the opportunity to fix things at the source.

When we did our 10-year retrospective study on Avandia, we learned that problems were evident as early as 2004. GSK would have had time to change their label and marketing, instruct physicians, and educate patients. Maybe then in 2008 lawsuits would not have been the recourse patients/caregivers felt that they had to take. Maybe it didn't have to cost GSK so much in legal fees and consumer trust.

When we studied Actos earlier this year, we learned that Takeda faces some real problems with Actos that could impact approvals for future indications. Bladder cancer, bone fractures, and cardiovascular risks are not going away. We believe that Takeda needs to address these risks now for both their current diabetes patients as well as for new trials in different disease states..

So why isn't pharma being more proactive in pharmacoviligance as well as efficacy studies?

We believe that observational research and surveillance studies need to start as soon as a drug or device is in market. It is not only in the best interest of the patient but it is also ultimately in the best interest of the company and the industry. The contributors to the article I read were mostly from non-manufacturers like we are at Wool Labs.

How do we get more of the manufacturers on board?

Too Many Diabetes Drugs Simultaneously and Drug Interactions

I have been working on the analysis of a new study we just completed focused on 18 oral diabetes medications.

Part of the analysis is looking at the medications that patients are taking and the potential impact on the performance of their diabetes drugs.

First, I am struck by the fact that many patients are on many drugs simultaneously. It seems that if one drug is not working, then they are prescribed another to add on top without any analysis of why that initial drug didn't produce the desired results. Yes, some patients are on a more obviously structured approach of shorter-acting combined with longer-acting products. Others, though, seem to have the kitchen sink thrown at them. This approach seems unique to diabetes type II. I can't say that I see this in anyother disease state; even cancer with its cocktails and combination therapy is quite disciplined.

Ok, so what are we seeing. First, patients get prescribed a drug at diagnosis, not uncommonly, Metformin. So patients' initial physical response is supposed to be (1) reduction in blood glucose, (2) reduction in hA1c, and/or (3) side effects or not. If the patient's numbers don't improve, I typically don't see evidence that the patient and the physician sit together and ask why. (We'll skip the fact that physicians tend to ignore patient complaints of side effects with Metformin and therefore, patients are not taking the drug as prescribed in many, many cases - which would be why).

What we do see is that patients will be prescribed another drug to put on top of Metformin, not always switched, just added to. And sometimes that happens again and again. Drugs don't always get removed from the regimen, just added to. And dosing schedules get complicated.

Each time a drug is added, several things can happen. First complicated regimens are hard for patients to keep up with. Second, these drugs can have interactions both with each other and with other non-diabetes drugs. Some diabetes drugs interfere with one another creating hypoglycemia and/or unstabled blood glucose numbers, which is maddening for patients who can't seem to get their numbers under control. Next, physicians see the lack of control and more often than not, blame the patient without always scrutinizing the whole process.

At some point, sometimes quite confusingly for patients, the drugs all get swamped out for a new set. Sometimes patients just start on one new drug. But the pattern starts again of adding but not subtracting until the next critical mass happens.

The pattern doesn't necessarily change if the patient starts on insulin. At first, insulin seemsused alone but that doesn't always last and oral meds are added back.

At the same time, patients are working changing their diet and exercise patterns, which also impacts drug performance at the original dosing regimen many times resulting in hypoglycemia. And with patients on multiple drugs at one time, the non-diabetes drug interactions grow - birth control and blood pressure meds, NSAIDS, thyroid drugs, some antibiotics, asthma meds - all increase risk for both hypoglycemia and hyperglycemia simultaneously. No wonder so many people can't get their numbers under control.

The whole process doesn't seem the best way to tackle what is called an epidemic. Many patients do figure it out with hard work and lots of research. But a lot more don't.

So more drugs on the market is not going to make this better. Diabetes needs a better approach that figures out why some medications work and others don't, how diet and exercise really impact medication needs, and how to reliably stop the advance of the disease. The kitchen sink approach is not a long-term strategy.