At Health and Life, we have been grappling with the question – what drugs are relatively unknown today, the Winter of 2010, but will be major players 5 years from now?

To get an answer, we needed a better question.  What pharmacological innovations will allow the necessary marketing to turn a treatment into a major success and hopefully better treatments for patients?

This list of ten treatments spans from the already approved to the investigational.  Each has some aspect that shines through.  Read for curiosity’s sake or to know where the market is going.

Anticipated Blockbuster Drugs

1) Byetta once weekly is a medication we like and think will do well.  Chemically, it acts like glucagon-like peptide 1, a substance released when you eat food that does a bunch of nifty things.  Byetta reduces your appetite, blood sugar, and helps improve important markers associated with diabetes.

In one study, 75% of those on Byetta with diabetes lost weight.  That’s pretty impressive.

Byetta is on the market right now and is taken twice daily by injection.  A once weekly form is up for FDA review which is significantly more convenient and could even improve results.  Some studies have shown that once weekly treatment slightly improves HbA1c, an important diabetes related marker, with 77% achieving target levels.

The main concern is the advent of similar medications in the same class and that Byetta might not completely pass the upcoming FDA review.  One analyst commented that the movement of the FDA review from March 5 to March 12 is a sign of bad news and a possible request for more data.

A delay for Byetta once weekly could cost it significant market share.

Market: People with Type II diabetes, a large market and one that is only growing.  The upcoming FDA decision will determine how quickly Byetta once weekly can enter the market.

2) Stelara should do well.  It is a very good treatment for psoriasis, achieving 75% reduction in plaque area and severity in at least 2/3 of those who take it.  This improvement is large.  We’re talking about going from almost complete skin coverage in psoriasis to almost clear skin in some patients.

Studies have shown its superiority over traditional psoriasis treatments.

That’s a good start but not a clear winning advantage.  Studies that show superior efficacy of one treatment over another might not receive the widest distribution, or are susceptible to challenge.

The second part that makes Stelara so exciting is that it only needs to be given 5 times a year.  This is a lot better than most of its competitors.  Enbrel, for instance, needs to be given weekly.  Since delivery of both is by injection that is a significant advantage.  Think 5 injections per year, or 52 injections.  Which would you prefer?

Stelara might even have uses for other conditions beyond psoriasis.

Market: The psoriasis market is fairly large but has a fair amount of competitors.  Considering the advantages Stelara has, however, it should do well.

3) Valdoxan is a new antidepressant that has some exciting new biochemical activity – it avoids the serotonin pathways that are so popular and instead works on melatonin.  Its novel activity is already making for a great marketing angle.  (Skeptics will recall that there are already antidepressants that aren’t serotonin based.)

Because of its new mechanism of action, it’s likely that Valdoxan will have significantly less side effects compared to the SSRIs.  If it overcomes the concerns around it, efficacy, liver issues, suicidal ideation – two thirds of which apply to the SSRIs, Valdoxan could easily be a blockbuster.

Market: 10% of Americans are on antidepressants, and rate of use appears to be still growing.  A very significant percentage of people who start antidepressants report side effects as a serious issue.

4) Provenge is a novel treatment for prostate cancer.  It works well but there have been concerns about its ability to get FDA approval.  We strongly think it’s going to make it.  But we’re not sure is how well it will sell.

Here’s why.

First, Provenge is made by harvesting blood cells from a patient, training them to develop an immune response to certain prostate markers, then putting them back in.  This is a complex, multi-step procedure that is impossible to fully standardize.

It is a far cry from manufacturing 100,000 pills all with the exact same chemical composition.

The FDA in 2007 asked for more data on Provenge despite it showing very significant survival benefit because the trials failed to meet their primary goal.  The primary goal was to increase the time it took for the cancer to progress.  Critics were outraged because the trials did show a significant increase in life expectancy.

A new study on Provenge designed with the primary goal of increasing objective survival recently released data showing it met its goal.

We’re talking about a 35% increase in life expectancy in metastatic, androgen independent prostate cancer patients who take it.

That’s huge.  We expect Provenge to get approval despite its complexity because it is a proven life-prolonging treatment and the new study meets most of the concerns the FDA raised.

Market: Men with prostate cancer, a condition that kills 28,000 people yearly.  Some analysts predict 10-20% market penetration by Provenge.

5) Apixaban is a new cardiac medication being developed for a variety of conditions, ranging from preventing deep venous thrombosis to being used as a prophylactic treatment after an acute coronary event like a heart attack.

It targets a key factor in the blood clothing pathway.

Those indications are a tremendously sized market.

Most importantly, Apixaban seems to work fairly well.  In one study for preventing thrombosis after knee replacement, the problem of blood clots forming after surgery, 9% of those on Apixaban had an adverse event, as opposed to 15% of those on Lovenox and 26% of those on Warfarin.  Those type of data makes specialists’ jaws drop.

Also in its favor, Apixaban can be taken orally and has pharmacological behavior that is quite promising, like minimal drug interactions.  Lovenox and Warfarin, two of its existing competitors, must be given by injection and Warfarin has many drug interactions

Market: Potentially very many cardiac related uses.  While Apixaban seems very promising, it has not yet been FDA approved, while competitors like Rivaroxaban and Dabigatran are entering the market in Europe and Canada.

6) Lyrica is an interesting medication and its variety of action means it can be prescribed to an awfully large audience.  Lyrica reduces anxiety and pain and while also acting as an anti-convulsant.  This is the same profile of activity that is exhibited by the benzodiazepines like Xanax and Valium.

Xanax and Valium have been extremely, extremely successful despite their high risk of addiction and abuse.  (Or perhaps because of…)  The important thing is that it seems that Lyrica has less potential for abuse and addiction.

At the moment, Lyrica is approved for a variety of conditions like fibromyalgia and diabetic peripheral neuropathy.  Pfizer is researching its use for restless legs syndrome, sole therapy for epilepsy, and varied pain conditions.

And they are filing an application right now for its use in Generalized Anxiety Disorder (GAD).

Market: Lyrica is already approved for a variety of conditions like fibromyalgia.  We expect Pfizer to drastically increase its market by getting an indication for GAD as well as possibly over conditions

7) Sutent is a tyrosine kinase inhibitor that inhibits a variety of cancer related pathways.  It is less specific in its targets than other tyrosine kinase inhibitors which has proven to be extremely important.  A wider range of therapeutic action can mean more efficacy as well as ability to work as a treatment for different types of cancer.

Sutent has shown its mettle for treating renal cell carcinoma and as a back up therapy for gastrointestional stromal tumors.  Since it affects several cancer related pathways, it is highly likely it will show efficacy for other cancers as well, especially pancreatic.

Sutent costs around $50,000 a year.

Market: Sutent is currently used for renal cell carcinoma and as a back-up therapy for GIST.  Pfizer, however, is running trials of Sutent for Colon, Lung and Prostate Cancer and others – a positive indication for any of which greatly expand its uses.

Not to mention that Pfizer is applying for registration to use Sutent for a type of Pancreatic cancer.

8) Belatacept is a treatment to help prevent rejection of kidney organ transplants.  The benefits it has may include lower risk of developing diabetes and better blood levels control with a lower intensity regime in transplant patients.

You might just have to take Belatacept every few weeks as opposed to twice daily for Cyclosporine, the current standard of care.

Not to mention that studies have shown that patients on Belatacept have higher kidney function as well as better blood pressure levels.

Most concerning is an increase in rates of acute kidney rejection on those taking Belatacept.  On the other hand, there has been cases of rare conditions like progressive multifocal leukoencephalopathy in those on Belatacept.    Still, an FDA advisory panel just heavily voted for its approval, saying that such issues can be monitored over time.

There has not been much innovation in the transplant medication field, and Belatacept seems to have some advantages over current therapy.  We expect it to do well.

Market: 16,500 kidneys are transplanted per year in the USA

9) Benlysta

Lupus, a strange autoimmune condition, is an open market.  Anywhere from 250,000 to 1.5 million Americans have some form of it, and there has been no new medication in several decades.

Benlysta, a new lupus treatment, could shake things up.  It is a monoclonal antibody to B-lymphocyte stimulator which plays a role in the development of the immune system’s B-cells.  The mechanism of action is promising.

That said, the data have shown lackluster efficacy. In one study, 57% of patients responded to a higher dose of Benlysta compared to 43% response in placebo.

Still, the market is huge and wants a new medication.  Projections of sales for Benlysta, if it makes it past the FDA, go as high as $4 billion annually.

It is a medication worth watching but we would bet against it.

Market: Anywhere from 250,000 to 1.5 million Americans have some form of lupus

10) Intuniv is a new non-stimulant treatment for ADHD made by Shire.  Crucially, it seems to be more effective than Strattera, the first non-stimulant medication approved for ADHD which most people agree was a failure.

We expect it to be a winner because there is a significant demand for non-stimulant therapy for ADHD.  Add to that the proven power of Shire to market new ADHD pharmaceuticals (their launch of the stimulant Vyvanse has resulted in rapidly growing market share) and you get what will likely be a significant hit.

Market: Up to 10% of children and 5% of adults have ADHD.  30% of people either don’t respond to or have significant side effects from the stimulants like Ritalin and Adderall.

Intuniv can be used alongside traditional treatment or as monotherapy.  Our analysis has hinted at potential side effects like high rates of fainting – if those issues don’t rise like a specter, expect Intuniv to sell quite well.

Health and Life is proud to be hosting the 32cond edition of the Cancer Research Blog Carnival.

Why do we participate?

The Cancer Research Blog Carnival (CRBC) is a fun way to connect bloggers across different areas with one goal – to blog about some area of cancer research.  We’ve learned a lot from reading the past posts and hope that our edition of the CRBC will have some good ones!

Any preferences for entries?

Anything to do with cancer research is good.  That said, we at Health and Life are pharmacology buffs.  We love learning about medications.  Submissions relating to cancer chemotheraputics are especially welcome.

If interested, you can use this form to submit an entry.

Another week, another Pharma News Update from Health and Life.

#1 Glaxo Strikes Back At Critics – But It’s a Swing and a Miss

The biggest health news item over the last two weeks is what is shaping up to be yet another major health disaster.  Avandia, a popular diabetes medication, may have caused many heart attacks.

A medication in the same class, Rezulin, was removed from the market in 2000 due to liver problems.

Last week, Glaxo, its maker, tried to defend itself, but this piece argues it was a swing and a miss.

Seven of [the nine studies sponsored by GSK] showed either that there were some increased side effects in patients taking Avandia, including heart attacks, or that Avandia wasn’t as effective as other treatments.

#2 Back-and-forth on Seroquel as trial begins

Seroquel, an extremely popular antipsychotic, likely causes metabolic issues that can lead to diabetes.  It’s just something that – unfortunately – the antipyschotics tend to do.

This major lawsuit, the first one to put Seroquel on trial, alleges that AstraZeneca suppressed that risk in favor of aggressive marketing.

AstraZeneca’s lawyers said that Seroquel doesn’t cause diabetes, blaming plaintiff Ted Baker’s disease on his diet and lifestyle.

#3 The Most Expensive Drugs Today

Forbes reports on the most expensive drugs, with Soliris, costing $409,500 a year, coming in first.  Wowza.

But remember, some of these medications are for sickness that are very, very rare.  Some of which are so rare that there are only several thousand people with them in the world.

#4 These Drugs Generated Most Adverse Event Reports

PharmaLot, an excellent source of industry news, provides this analysis of which medications caused the most adverse event reports in the third quarter 2009.  Not surprisingly, Avandia is on there.

#5 An Untouched Market Waiting to Be Captured

30% of prescriptions for diabetes medications like Januvia or Actos are not filled.

28% of prescriptions for cholesterol medications like Lipitor or Crestor are not filled.

This represents a huge opportunity for Pharma companies.  Orders for their product are being made just not filled.  Marketing that increases the rate of prescriptions that are actually filled could be an easy way to make more money.  (And presumably improve the health of those taking them.)

#6 Transplanting Future Revenue

Belatacept is an exciting and promising new medication for preventing organ transplant rejections.  There has not been much innovation in this field for a while, and it is fairly important.  When you get a kidney transplant, you’d prefer that your body not try to kill the new kidney.

That said, documents released on Monday raise concerns about Belatacept’s potential to lead to complications like progressive multifocal leukoencephalopathy.

#7 Scientists Find Possible Cause of Tamoixfen Resistance

Who can forget that magical moment when the Human Genome Project finished sequencing the first human genome?  The only problem is that since then treatments based off genetics have been somewhat slow to come.

It seems that resistance to Tamoxifen, a very common treatment for breast cancer, may be predicted by the presence of a gene.  Breast cancer is extremely common and any treatment improvements can make a major difference.

#8 Extended-Release Mirapex Approved for Parkinson’s Disease

Mirapex ER, an extended release form of Pramipexole, was approved last week as a treatment for Parkinson’s Disease.

#9 Hints of Cancer Risk from Diabetes Drug Victoza

Will Victoza, a new diabetes medication, succeed?  Despite having some advantages, there has been a lot of complications that are getting in its way.  And it is likely only a matter of time before a once weekly form of Byetta, its competitor, is approved.

Some animal models have hinted at carcinogenicity in Victoza.  Such models aren’t necessarily examples of good science but this certainly won’t help Victoza in its extremely competitive market.

Some of the most interesting – on a pharmacological level – medications I’ve encountered are cancer treatments.

Take Tamoxifen, for instance.  This highly effective treatment for certain types of breast cancer works because it blocks the effects of estrogen in the breast.  Since estrogen plays a role in getting cells in the breast to grow, this has significant anti-cancer effect.

Yet there is a downside.  Tamoxifen acts like estrogen in the uterus, which increases risk of uterine cancer over time.

I love analyzing medications and that extends to cancer treatments.  But it is a more challenging interest than for other treatments.

When I look at an asthma medication, things are simpler.  Does it improve breathing?  Does it reduce the need to go to the emergency room?  Things get thorny when common medications have black box warnings, but still not too hard.

Cancer medications are challenging on many levels, intellectually, emotionally.  You are confronted with statements like “those on medication X lived 6 months on average, while those on placebo lived 4 months on average.”

The best part is finding new treatments that offer hope.  Even then I am weighed down by knowledge (or, more accurately, lack of knowledge) and the challenge of grappling with exceptionally complicated information.

Take the aromatase inhibitors.  Some studies say that they are a better treatment in post-menopausal woman than tamoxifen for preventing breast cancer from coming back.

The aromatase inhibitors were so much better that a study I look at was actually stopped to give participants the opportunity to switch to them.

That’s wonderful, right?

Yes.  That said, one study I looked at showed superiority of the aromatase inhibitors in preventing breast cancer recurrence but showed an increased rate of other cancers.

Let me end this post with some thoughts on where cancer treatments are going.

Future Cancer Therapies

The goal of future cancer treatments is to find the molecular pathways that are deregulated in cancers and target them alone.  Think doing a targeted missile strike on a house instead of carpet bombing a city.

The limitations to targeted treatments include the sheer complexity of cancers.  You can knock out one pathway that leads to cancer formation only to have the tumor adopt another approach.  Cancer doesn’t form when just one thing goes wrong, rather it happens when many things go wrong at once.

Resistance often arises.  Cancerous cells are full of nasty tricks, like developing pumps that get rid of the medications you throw at them called Multiple Drug Resistance pumps.

New cancer treatments for the past few years have tended to fall into two categories.  There are the tyrosine kinase inhibitors which are almost all named something that ends in “nib” (Lapatinib, Gefitinib, and Sunitinib).  Then there are the monoclonal antibodies that have extreme specificity to some molecular target.

The tyrosine kinase inhibitors try to stop specific pathways associated with the development of cancer.  Tyrosine kinases are a fairly large family of receptors and play a very large role in the regulation of cell growth.  Their efficacy can range from phenomenal, Gleevec, to disappointing, Gefitinib.

The monoclonal antibodies have a variety of targets but all try to knock out some key aspect involved in the cancer.  Herceptin, for instance, binds to HER2 receptors that are highly overexpressed in a significant percentage of breast cancers.  Avastin binds to VEGF, a messenger that tells blood cells to grow, feeding the cancer.

There are additional areas being investigated.  While unlikely to be used for at least several years, PARP inhibitors may play a role in treatment of breast cancer by increasing cells susceptibility to traditional chemotherapy.