A safety review of GSK’s Avandia, under fire and intense scrutiny for its role in the possible development of cardiac adverse effects is nearing completion. In spite of the continued negative press, the pharma company has issued a thirty page rebuttal [PDF] of the Senate Finance Committee’s report alleging those safety issues.

The pharma company faces an uphill battle. In the wake of 24-hour, always on news cycles which seemingly filter only stories of negative sensationalism, it should be taking its damage control cues from Toyota these days.

Among the report’s most “glaring omissions” is its lack of discussion about the final results of the ADOPT, DREAM, or RECORD trials, the company said in a release. It said data from these three trials were reviewed by an FDA advisory committee in 2007 that voted overwhelmingly to keep rosiglitazone on the market.

Perhaps, but the issue now is that GSK chose to keep this information from the meta analysis of these trials from prescribers and patients, according to the Cleveland clinic physician responsible for bringing this data to the forefront. | LINK

• Vanderbilt University (my undergrad alma mater) has announced that it has access to a special blood test that can predict a patient’s risk for heart disease. Using genomic factors, along with the patient’s age, history of stable chest pain, and gender — the assay (dubbed Corus CAD) offers a non-invasive alternative in stratifying coronary disease risk.
  

  The test was developed as a part of a new medical field called genomic medicine, which enables doctors to further personalize patient care based on the unique genomic makeup of individual patients — an important factor for many visiting the doctor. For this reason, the blood test interests many physicians.

  Count me among those interested.

• On a more dour note, there is renewed interest in the recall of rosiglitazone (Avandia), the Glaxo drug with known associations in causing cardiac disease and risk of death; confidential studies via officials in the FDA are recommending the drug’s withdrawal from the market, potentially leaving Pfizer’s pioglitazone (Actos) as the only market alternative in this class to treat diabetes mellitus, type 2.
  

  The company has faced criticism that it has known about the heart-attack risks associated with Avandia for years. Glaxo added a “black-box” warning to Avandia in November 2007 that says the drug can cause or exacerbate congestive heart failure. The company has also faced accusations that it attempted to intimidate scientists and doctors outside the company who raised questions about the safety of Avandia. The company has said that it didn’t try to intimidate anyone.

Pharma giant Pfizer announced today that it will be funding a Stanford University-led initiative to provide industry continuing medical eduction (CME) which will not depend upon direct corporate “influence” on the curriculum. Sounds pretty ironic, at best, and downright insidious at worst. According to Stanford , there is room for the unbound dissemination of medical didactic method free of corporate influence while allowing Pharma industry financing.

“We believe that the education of practicing physicians should be based solely on the best scientific evidence presented in a fair and balanced way,” said Jackler, professor and chair of otolaryngology. “Unfortunately what’s happened is that the partnership with industry has led CME astray, to the point where the curricula are too often biased toward business interests.

“So we set out to see if industry would be willing to partner with us to create a high-quality curriculum, under the condition that Stanford faculty would choose the topics and design the curriculum independent of the relationship with industry,” he added. “We sought not to prevent partnerships with industry, but rather to redefine it.”

Redefinition. I guess it’s all in the semantics. | LINK

Pharma has no comment on it. Congressional Democrats are wasing no time in investigating it. The concern over Pharma’s recent move to inflate drug prices on prescription branded agents is drawing scrutiny from the powerful House Ways & Means Cmte. As much as a 9 percent increase for the most widely prescribed medications today has apparently been implemented. The Dept. of Health & Human Svcs. has also been asked to investigate. Against the backdrop of strident efforts to reform what are seen as excessive cost drivers in the healthcare marketplace, the price increases set by Pharma represent an easy target by lawmakers.

Alleging the gamut of rationale to include everything from pre-emptive revenue enhancement ahead of reform^[1] to outright price gouging, lawmakers have also asked the General Accounting Office to come up with a proposal to continually monitor Pharma for such increases for the benefit of Congress. If Democrats’ concerns pan out, it would question Pharma’s motives, especially in light of the possible benefits to the industry as the result of reform. | LINK

1. Drugmakers have recently backed Democrats’ plan to overhaul the U.S. healthcare system, making a deal with some senators and the White House to provide around $80 billion in savings and rebates over 10 years. Some lawmakers are concerned price increases could be method to recoup expected loss of profit as the result of final reform bill. [↩]

How can a drug’s study results involving just over 200 or so participants shake up healthcare policy? If the name of that drug is Zetia, there’s already enough political baggage that is making that happen. Statements like the following from the study’s lead investigator are pretty definitive — and to Merck, pretty damning:

“The results are very clear,” says lead investigator Allen Taylor of the Medstar Research Institute. “Niacin was superior.”

You read right. Niacin, a commonly used (and cheap) B vitamin did a significantly better job of shrinking artery plaque than the billion-dollar blockbuster ezetimibe (Zetia), also a component in the top-selling agent, Vytorin. Critics may claim — and rightly so — that this trial, involving just 208 people — is just too small to have a significant impact on clinicians who prescribe Zetia and/or Vytorin to treat this country’s number one killer — heart disease. However, there is no denying that the impact beyond this result is huge and is based upon the fact that ezetimibe’s lackluster trial data was the third iteration in two years^[1] to challenge the effectiveness of one of the world’s most popular heart drugs, with $21B in sales since it was introduced in 2003.

The result was so pronounced that the study was stopped in 14 months. Although the use of ezetimibe, an expensive branded drug not automatically covered on all drug plans, was not found to be superior to the much, much insanely cheaper niacin, it does represent a niche for doctors treating patients who have yet to reach cholesterol goals and who cannot tolerate some of the more bothersome adverse effects^[2] of niacin. Of course, Merck “stands by” Zetia, but they have to be preparing themselves for the inevitable onslaught of patient concern of paying in a major way for a drug found to be no better than a lowly B vitamin in the treatment and secondary prevention of heart disease. | LINK

1. Last year, the ENHANCE trial showed Vytorin, made of ezetimibe (Zetia) and simvastatin (Zocor), did no better job of treating clogged arteries than simvastatin alone. [↩]
2. These include diarrhea; dry skin; headache; itching; stomach upset; temporary skin redness, tingling or feelings of warmth and flushing. [↩]

If you’re a pharma company that thrives on innovation (and, really, are there any which don’t?), and you’ve got to get product out; you have two things working against you: an economy which won’t begin to see its brightest days until year or so from now, and huge stakes on whatever decision lawmakers fashion out of the health reform debate. Although high powered lobbyists for the drug industry probably have your back, you’re still a little reticent about unleashing a new agent.

Then again, you could just throw caution to the wind and release a drug, make news at the same time, and pray for immediate profits to please shareholders so that they can keep the investments coming based upon a portfolio which aches to show any improvement over the previous quarter’s.

That’s the route Schering-Plough has taken by releasing Saphris (asenapine), a new agent in the treatment of bipolar disorder and schizophrenia. It’s joining an already crowded field of other drugs in its class to treat these disorders. Time will tell if it makes a difference in patients’ lives, but for its pharma company, it better be sooner — as its spin has already started.

“Basically these drugs have tended to fall into two baskets,” Robert Consalvo, director of global product communications and advocacy relations for Schering-Plough, says. One group is potent but has side effects such as weight gain or blood sugar issues, while others are better tolerated but not as effective, Consalvo explains. “We see asenapine combining the potency with that acceptable metabolic profile.”

[...]

If that’s the case, then asenapine would make a contribution to the field, notes Jeffrey Lieberman, MD, the Lawrence E. Kolb Chairman of Psychiatry at Columbia University’s College of Physicians and Surgeons and director of the New York State Psychiatric Institute. “But the data that have emerged so far haven’t shown that,” he says. “The studies haven’t shown that it provides any unique therapeutic advantage. The main contribution is that clinicians and patients will have yet another choice.”

Choice. It’s what happens when innovation isn’t disrupted. How will it continue to be financed? | LINK

Is PhRMA reneging on statements its chair made about a “deal” with the White House to prevent Medicare from negotiating with Pharma as part of Obama’s health reform package? The lobby’s vice president is refuting claims that chairman (and former Louisiana congressman) Billy Tauzin confirmed a deal had been reached between the two parties that would leverage the government’s spending on drugs beyond an agreed amount of cost savings over the course of a decade.

At stake is over $150 million in ads by the influential lobby supporting the Obama administration’s efforts at reform. If Congress decides to pass legislation prohibiting industry price controls at the hands of Pharma, allowing Medicare to negotiate prices across the board, could this be a PR firestorm just waiting to happen for either side? The president may have gained support from Pharma for his reforms, but at what potential costs to him, fellow Democrats, and his constituency? | LINK

The FDA is drafting guidelines for medical device and drug makers concerning the portrayal of information on advertisements about their products. What’s interesting about this move is that, in addition to the usual information regarding the use of outright bogus claims as a violation of FDA rules, the agency also advises against the use of stubtle advertising techniques which may portray a drug or device as wholly benign amid known adverse effects and rigorous monitoring schedules — a practice they say is “deceptive” and “discordant”. | PDF LINK

In the march toward his overall healthcare reform plan, President Obama has reversed a George W. Bush administration regulation that gave the feds the ability to trump state governments’ decisions concerning liability with medical devices. Device makers were essentially shielded from healthcare consumer lawsuits Bush generally deemed as “frivolous” in nature. Also, Big Pharma was helped by such actions since the FDA often did not follow regulatory guidelines in implementing new drug indications.

Obama in a two-page memo wrote that federal agencies and departments could claim state law is pre-empted by federal law only when there is a well-defined legal basis. The memo stated that state laws are important because they supplement federal regulations. “State and local governments have frequently protected health, safety and environment more aggressively than has the national government,” Obama wrote.

If efforts at stopping government pre-emption give the patient more of an incentive in trusting public delivery of healthcare, at the same time cutting massive bureaucratic waste from lack of government regulation in healthcare delivery, this effort of Obama’s is to be praised. On the contrary, concerns over a flurry of patient lawsuits from Republicans should be a nonissue since Obama acknowledges the rights of individual states in this case. | LINK

Out of the distribution of the hundreds of billions President Obama has signed into law as part of the ‘09 Recovery & Reinvestment Act, it’s easy to overlook the relatively “minor” earmarks as part of this stimulus package with respect to his commitment to healthcare reform. One of those areas is in pharmaceutical research. However, it probably isn’t what you’re thinking when you hear that word.

Via his healthacare stimulus package, Obama has asked for researchers to study the effectiveness of drugs after they have gained approval by the FDA. Strictly speaking, comparative effectiveness research, as it’s called, is the study of utilization patterns, costs due to procurement, costs due to adverse effects, insurance coverage, and expected outcomes among drugs in certain classes. This data compares drugs in the same pharmacologic classes to find the most economically efficient and medically effective ones. It’s just another tool to examine the effect of a major source of the cost of healthcare today — the pharmaceutical industry. | LINK

It’s a marriage of self interests among Pharma and Big Insurance. Merck and Cigna just announced a partnership which involves the applications of drug discounts from the pharma company as a benefit to the healthcare payer if patients “perform” well on those covered drugs.

What are those drugs? Two key players in the next generation of agents Merck is positioning for heavy market growth and consumer use — Januvia and Janumet, both of which contain the main chemical ingredient, sitagliptin. Merck is not requiring that those drugs be solely repsonsible for good diabetes control in patients on other anti-diabetic drugs, of course; but the designation of Januvia and Janumet as “perferred agents” in the Cigna formulary makes this sort of surveillance a little easier — which is why the insurer is in talks with three other drug classes. | LINK

This has to be the absolute sanest thing the FDA has done in quite a while: reject a drug (for an indication to treat depression) which appears in the same class as drugs used to treat acute psychosis and chronic schizophrenia (!)

A committee of Food and Drug Administration advisers said Seroquel XR was safe enough for treating some patients with depression but opposed use of the drug for fighting anxiety given the serious side effects.

The panel voted 6-3 that Seroquel XR had acceptable risks if it was added to other medicines to find a workable combination to alleviate depression. Several panel members stressed that doctors should try other treatments for depression first before deciding to add Seroquel XR.

Okay, so the FDA’s stance was not exactly prohibitive on the use of Seroquel to treat depressed mood; it was more conciliatory (almost as if its pharma company requested it)…

The panel split 4-4, with one abstention, when asked if it was safe enough to use Seroquel XR as the only treatment for depression in some cases. Panelists said there were safer medicines that should be tried if only one medicine was going to be used.

Does that mean that physicians **won’t** prescribe it for depression as a first-line? Heck, they already give the stuff for sleep. | LINK

• Popular anticonvulsant (with a multitude of off-label pain uses) gains approval to go generic.
• A Web-based provider of care analytics has come up with a prostate cancer screen. The cynic in me says it’s a new look to an old unresolved problem.

Through a web-based tool, men enter the results of their PSA test history and personal information such as height, weight and health history. This information is compared with up to a million case studies and outcomes from other men with various prostate conditions. Finally, the system may suggest a medical detective process for doctors and their patients in their efforts to detect non-cancerous prostate conditions and improve prostate cancer screening, the company said.

• Lilly is trying very hard to get a novel neuroleptic to market; it’s not going too well.
• Crestor, an popular cholesterol drug, to protect against venous blood clots? | VIDEO
• CA spice company linked to Salmonella outbreak. | LINK