FDA approves Victrelis (boceprevir) for Hepatitis C

The U.S. Food and Drug Administration today approved Victrelis (boceprevir) to treat certain adults with chronic hepatitis C. Victrelis is used for patients who still have some liver function, and who either have not been previously treated with drug therapy for their hepatitis C or who have failed such treatment. Victrelis is approved for use in combination with peginterferon alfa and ribavirin.

The safety and effectiveness of Victrelis was evaluated in two phase 3 clinical trials with 1,500 adult patients. In both trials, two-thirds of patients receiving Victrelis in combination with pegylated interferon and ribavirin experienced a significantly increased sustained virologic response (i.e., the hepatitis C virus was no longer detected in the blood 24 weeks after stopping treatment), compared to pegylated interferon and ribavirin alone, the current standard of care.

Changes to Clinical Studies of Vorapaxar

Yesterday, Merck announced changes to the clinical studies for vorapaxar. Vorapaxar is a selective PAR-1 (Protease Activated Receptor) Thrombin Receptor Antagonist designed to diminish thrombosis (clot formation).

The combined Data and Safety Monitoring Board for the two studies has reviewed the available safety and efficacy data, and made recommendations for study changes to the chairpersons. The study chairpersons have agreed to implement these changes, and communicated the following information to study investigators:

* In the TRACER study, patients will discontinue study drug and investigators are to begin now to close out the study in a timely and orderly fashion.

* In the TRA-2P study, study drug will be continued in patients who had experienced a previous heart attack or peripheral arterial disease (approximately 75 percent of the patients enrolled in the study), and will be immediately discontinued in patients who experienced a stroke prior to entry into the study or during the course of the study.

You can read more about their changes here on the Merck website.

An update on vorapaxar (SCH 530348)

Here's an update on vorapaxar from the American Journal of Cardiovascular Drugs: 1 December 2010 - Volume 10 - Issue 6 - pp 413-418

Abstract

Merck & Co. is developing vorapaxar (SCH 530348), a thrombin receptor antagonist, for the prevention and treatment of arterial thrombosis. Vorapaxar is currently being evaluated in two large-scale multinational phase III trials (TRA*CER and TRA 2°P-TIMI 50) for the treatment and prevention of cardiac events in almost 30 000 patients with acute coronary syndromes and those with prior myocardial infarction or stroke, as well as patients with acute coronary syndrome and those with peripheral arterial disease. This review discusses the development history and scientific profile of this new compound.

Click here for more details.

Vorapaxar: Merck's most promising experimental medicine?

Earlier this month, I was reading a Reuters report on vorapaxar (previously known as SCH 530348). Here's what the story said:

Industry analysts have dubbed Vorapaxar, now in late-stage trials among thousands of patients with a history of heart disease, Merck's most promising experimental medicine. Cowen and Co predicts it will generate annual sales of $1 billion by 2015.

Why such optimism? Vorapaxar does not appear to increase bleeding risks. Here's what the report says:

Merck & Co's (MRK.N) experimental drug to prevent blood clots is unlikely to increase bleeding risk, a potential boon to heart patients that would distinguish it from standard treatments...

What makes vorapaxar so unique? It has a different mechanism of action and if it's approved by the FDA, then it would emerge as the first of its class:

Vorapaxar works through a new mechanism -- by blocking a receptor to thrombin, a protein highly involved in the clotting process. The product, which Merck acquired through its $41 billion merger with Schering-Plough Corp last November, is widely known by its nickname TRA (thrombin receptor antagonist).

How to pronounce vorapaxar

People often struggle with drug name pronunciation. There's a drug that's currently in development called vorapaxar and it's a thrombin receptor antagonist or TRA. Most of us didn't learn about TRAs in medical school.If you're a cardiologist, you've probably heard of vorapaxar or SCH 530348.

Vorapaxar is pronounced vor" a pax' ar.

CHEMICAL NAMES

1. Carbamic acid, [(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(1E)-2-[5-(3-fluorophenyl)-2- pyridinyl]ethenyl]dodecahydro-1-methyl-3-oxonaphtho[2,3-c]furan-6-yl]-, ethyl ester, sulfate
2. Ethyl [(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(1E)-2-[5-(3-fluorophenyl)pyridin-2- yl]ethenyl]-1-methyl-3-oxododecahydronaphtho[2,3-c]furan-6-yl]carbamate sulfate

Here are a few other interesting facts:

MOLECULAR FORMULA C29H33FN2O4 . H2O4S
MOLECULAR WEIGHT 590.7
MANUFACTURER Schering-Plough/Merck
CODE DESIGNATION SCH 530348
CAS REGISTRY NUMBER 705260-08-8

Source: STATEMENT ON A NONPROPRIETARY NAME ADOPTED BY THE USAN COUNCIL (click here to access)

SCH 530348 is now vorapaxar (thrombin receptor antagonist)

What used to be a Schering-Plough pipeline drug is now a Merck pipeline drug. SCH 530348 is now vorapaxar and it's a new oral antiplatelet medication called a thrombin receptor antagonist, or TRA. If you're a cardiologist, you've probably heard of this compound.  If you look for it on ClinicalTrials.gov, you'll find the following studies:

• Trial to Assess the Safety and Effects of SCH 530348 in Japanese Subjects With Acute Coronary Syndrome (P04772)(COMPLETED)
• Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and Stroke in Patients With Acute Coronary Syndrome (TRA•CER) (Study P04736AM2)
• Trial to Assess the Safety of SCH 530348 in Japanese Subjects With Cerebral Infarction (Study P05005AM5)(COMPLETED)
• Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and Stroke in Patients With Atherosclerosis (TRA 2°P - TIMI 50) (Study P04737AM2)
• Safety of SCH 530348 in Subjects Undergoing Non-Emergent Percutaneous Coronary Intervention (Study P03573AM1) (COMPLETED)
• Trial to Assess the Ocular Safety of SCH 530348 in Patients With Atherosclerosis (Study P05183AM1)

FDA approves Cervarix

The FDA has approved Cervarix, a new cervical cancer vaccine. The current vaccine Gardasil is made by Merck and Cervarix is made by GlaxoSmithKline (GSK).

The FDA has approved CERVARIX® [Human papillomavirus bivalent (types 16 and 18) vaccine, recombinant] for the prevention of cervical pre-cancers and cervical cancer associated with oncogenic human papillomavirus (HPV) types 16 and 18 for use in girls and young women (aged 10-25).

Click here to read the press release on the GSK website.

Will Gardasil get approved for boys and men?

Gardasil is a vaccine made by Merck and it's currently indicated for girls and women to prevent cervical cancer that's often caused by human papillomavirus (HPV) infection. Will Gardasil get an indication for boys and men? After all, those same viruses (HPV) cause warts in guys. Guys are just as guilty for spreading HPV, so why not vaccinate them as well? Would it be possible to eradicate HPV? That would be quite a public health accomplishment. What if HPV suffers a similar fate as smallpox? (well, terrorists are trying to bring smallpox back, but I doubt that any terrorist will have much interest in HPV).

Pfizer and a $2.3 billion settlement

Wow, you don't hear about a $2.3 billion settlement every day. It's hard for me to even imagine that much money. According to several circulating reports, Pfizer will pay $2.3 billion for improper marketing of Bextra (Valdecoxib), which was removed from the market in 2005. Bextra was a COX-2 inhibitor. I remember when COX-2 inhibitors came out. Many people were so excited to see an NSAID that wouldn't harm the stomach. We saw tremendous success with Celebrex (Celecoxib) and Vioxx (rofecoxib). We thought they were going to be wonder drugs for older adults with arthritis, back pain, etc.

You probably know who made Vioxx (Merck). Do you know who makes Celebrex? It's Pfizer. Now, we're left with Celebrex as the only COX-2 inhibitor. I wonder if we'll see new COX-2 inhibitors emerge on the market.

Should your daughter get the HPV vaccine?

My wife and I have debated this topic. Should our daughters get the HPV vaccine? There are so many potential implications associated with this question. CNN has a story that asks the same question: Should your daughter get Gardasil, the vaccine against HPV?

Right now, Gardasil (made by Merck) is the only HPV vaccine that is approved by the FDA. There are other vaccines in the pipeline, but who knows if/when they will get approved. The FDA has been so slow these days. Someday, we'll probably have a single vaccine that includes all of these major shots. This way, you won't have to poke people multiple times. Kids (and adults) don't generally like needles.

HPV causes warts. It can also cause cervical cancer. So by vaccinating children, you could be preventing cancer. From a public health view, it seems like the right thing to do. However, HPV is also sexually transmitted. So if you're vaccinating children, what type of message are you conveying regarding sex and sexually transmitted diseases? If you tell your child "abstinence before marriage" and then give her an HPV vaccine, are you communicating mixed signals?

So what do you think about this topic? If you had a young daughter, would you have her get the HPV vaccine?

To read the CNN story, click here.

Generic drugs for BPH from Walmart

I was having a discussion with someone about generic drugs used to treat BPH or Benign Prostatic Hyperplasia. Since you can get $4 drugs Walmart, I decided to write a blog post evaluating generic drugs that are currently available at Walmart. I don't know how much the Walmart generic drug formulary varies from state to state, so this may not be entirely accurate. Plus, I imagine that these formularies are constantly changing.

Alpha-1-adrenergic antagonists

Here are the generic drugs on the Walmart $4 list:

• terazosin (on the $4 Walmart generic drug list) - generic form of Hytrin (made by Abbott)
  
• doxazosin (also on the $4 Walmart generic drug list) - generic form of Carduara (made by Pfizer)
  

Not currently available as generic drugs:

• tamsulosin or Flomax (marketed by Boehringer Ingelheim and Astellas)
  
• alfuzosin or Uroxatral (made by sanofi-aventis)
• silodosin or Rapaflo (made by Watson)
  

5-Alpha-reductase inhibitors


Here is a generic drug, but it is not on the $4 Walmart list:

• finasteride (not on the $4 Walmart list) - generic form of Proscar (made by Merck)
  

Not available as generic drugs:

• dutasteride or Avodart (made by GSK)
  

So, you can't get a 5-alpha-reductase inhibitors for $4 at Walmart, but you can find the alpha-1-adrenergic antagonists (and they are listed under "Heart Health & Blood Pressure").

FDA: Labeling Change for Leukotriene Modifiers

Leukotriene modifiers (also known as Leukotriene Receptor Antagonists) are common asthma drugs that have been rarely linked to something called Churg-Strauss syndrome (good trivia fact). The FDA has requested that certain drug manufacturers include a precaution in the drug prescribing information (drug labeling) regarding neuropsychiatric events (behavior, mood changes) that have been reported in some persons taking montelukast (Singulair), zafirlukast (Accolate), and zileuton (Zyflo and Zyflo CR).

• Singulair is manufactured by Merck.
• Accolate is manufactured by AstraZeneca
• Zyflo is manufactured by Cornerstone Therapeutics, Inc.
  

What is it about certain medications? Can we be certain that these are all drug-induced effects? If clinical studies are not designed to look for such findings, can we be confident that post-marketing data can be interpreted properly? Do these drugs really cause mood changes? Or, are these simply associations that have no causality? Pretty soon, every single prescription drug out there will have some type of black box warning about mood changes and possible suicidal behavior. Once that happens, everyone will be ignoring these warnings.

What Do You Think About Rezonic/Zunrisa (Casopitant)?

Rezonic/Zunrisa (Casopitant) is a new drug that's being developed by GlaxoSmithKline (GSK). The indications will be for:

• Treatment for Nausea/Vomiting -- Chemotherapy Induced
• Nausea/Vomiting -- Postoperative

How does it compare to Merck's Emend (aprepitant), which is also an NK-1? Get familiar with the results of an ASCO 2008 abstract titled, "Phase III results for the novel neurokinin-1 (NK-1) receptor antagonist, casopitant: Single oral dosing regimen for chemotherapy-induced nausea and vomiting (CINV) in patients (Pts) receiving highly emetogenic chemotherapy (HEC)." That's quite a title.

The conclusion is simple: A single oral dose of casopitant added to a regimen of OND/DEX provided a clinically significant reduction in the number of pts experiencing CINV events over the first 5 days after HEC. This benefit appeared to be maintained through repeat cycles. This regimen was generally well tolerated over all cycles.

Pharma Job Fair

Pharm Country Career Fair
Monday, March 30, 2009, 2pm to 7pm
Radisson Valley Forge
King of Prussia, Pennsylvania

Looks like you can get information about business school if you're interested in getting an MBA during these difficult economic times.

Companies include:

Aerotek Scientific, LLC
Almac Clinical Technologies
CSL Behring
Fox School of Business - Temple University
Globus Medical, Inc.
Merck Research Laboratories
Morphotek
Octagon Research Solutions, Inc.
Regeneron Pharmaceuticals, Inc.
Shire
Siegfried (USA), Inc.

Find out more at BioSpace: http://www.biospace.com/

Pegintron (Peginterferon alfa-2b) Receives Expanded FDA Indication

You may have already seen this on Forbes. On March 11, the FDA approved the combination of Pegintron (Peginterferon alfa-2b) and Rebetrol (ribavirin) for treating chronic hepatitis C in patients 3 years of age and older with compensated liver disease. This is now the first and only pegylated interferon combination therapy approved in the United States that is not restricted to treatment-naive patients. Treatment to this combination is often dependent on your type of hepatits C virus genotype. There is such a need for better therapies for patients with chronic hepatitis C in this country. So many people got infected by blood transfusions before 1992 when the medical community didn't know about hepatitis C.

Pegintron is manufactured by Schering-Plough. If Schering-Plough merges with Merck, then the new company will be called Merck, so things may get a bit confusing.

Merck, Schering-Plough, and now J&J/Centocor

The Merck/Schering-Plough merger/reverse acquisition may hit some problems according to some because of J&J/Centocor and the co-marketing of Remicade (infliximab). Golimumab is a similar biologic agent that is currently in development. It is supposed to be co-marketed with Schering-Plough, but I guess we're not sure what's going to happen if Merck and Schering-Plough join forces. All these pharma merges/acquisitions are starting to get pretty crazy. Some are forecasting that thousands of jobs may get cut, but no one seems to be sure where those cuts may occur. I guess we'll just have to wait and see what happens here. These are some incredibly dramatic times in the pharma industry.

Merck to Acquire Schering-Plough

It looks like Merck will be acquiring Schering-Plough in a $41.1 billion deal. But wait, it's a bit confusing. People are referring to this as a "reverse merger" and Merck's top executive, Chairman and CEO Richard Clarke, will lead the combined company, but Schering-Plough will be the surviving public corporation. The new company will be called Merck.

VGX Pharmaceuticals: PENNVAX and CELLECTRA

Dr. J. Joseph Kim (no, not me) is president and CEO of VGX Pharmaceuticals. We're both MIT alumni, so we share one similar connection. There have been some exciting news from VGX recently.

Here's the headline from a recent press release: "VGX Pharmaceuticals Proprietary DNA Vaccines Delivered with Electroporation Achieve Immune Responses Superior to Recombinant Adenovirus Serotype 5 (Ad5) Vectors"

That sounds very exciting to me because there is such a need for better vaccines. Plus, we really need an HIV vaccine. This press release deals with some results on the PENNVAX HIV Vaccine Program. Researchers have been working on delivering the PENNVAX™ DNA vaccines using a novel electroporation device called CELLECTRA®.

Collaborators include the University of Pennsylvania, VGX, and Merck. These results are truly exciting and they reflect what can happen when you apply novel technologies in healthcare. Perhaps we will see a safe and effective HIV vaccine someday.