Pharmaceutical companies might have used this year's meeting of the American Society of Clinical Oncology to show they can perform on a stage that had been traditionally dominated by biotechnology firms.

But some of the biggest biotech companies say it's too early to say whether the stakes are complementary or in competition.

Not only have pharmaceutical companies taken a greater interest in biologics, but they are also discovering that small molecules can compete with monoclonal antibodies and other targeted therapies that are currently delivered through an infusion.

"Big Pharma has been making in-roads in their traditional [market] of small molecules," said Fred Cohen, MD, president of consulting firm Pharma Growth Strategies. "They're capitalizing on their strengths."

GlaxoSmithKline, for instance, received significant attention for Phase III data on small molecule Tykerb (lapatinib), which nearly doubled the time to progression of HER2 positive breast cancer compared with chemotherapy alone. The company also noted that Tykerb appears to reduce the risk of brain metastases that are associated with this type of cancer.

Amgen meanwhile presented data on an oral antiangiogenesis and anti-tumor drug, AMG 706, which is currently in Phase II.

"There's more competition than ever before," said Jim Daly, senior vice president of North America commercial operations at Amgen. "What we're seeing here is that Big Pharma is doing biotech work, and you're seeing biotech doing Big Pharma work. More and more, companies are trying to become modality independent."

Drugs that can be taken orally have the advantage of being more cheaply produced and possibly better tolerated because there have fewer immunologic concerns, Cohen said.

But, he added, "The overall cancer market is growing. There's room for everyone."

Genentech, for its part, has been hoping to expand the indications for which its products are approved. It presented more than 200 abstracts for 20 types of cancer, many of which target tumors that are harder to treat, like brain, kidney, and pancreatic cancers.

It is also hoping FDA will approve Herceptin (trastuzumab) to treat early-stage breast cancer, which could give it a leg up on Tykerb, a drug still being studied for more advanced stages of the disease.

"Last year we obviously had a lot of data for a single meeting," said John Orwin, vice president of Genentech's BioOncology unit, who added that the company has spent the last year trying to bring those products to market.

He called the increased interest in targeted therapies "a validation of the approach that Genentech has taken for a long time."

The company also presented early data on using targeted therapies in combination, as well as on a new compound that induces cell death, or apoptosis. The compound, dubbed Apo2L and developed in partnership with Amgen, is being tested for its ability to induce apoptosis in cancer cells while sparing normal ones.

Cohen noted that the largest chunk of the cancer market continues to be supportive care, an area dominated by Amgen.

But Daly said Amgen is also going head to head with companies that are developing cancer treatments, as well as building its supportive care portfolio. He referred to this year's meeting as a "coming out party" for denosumab, which is being tested for osteoporosis, treatment-induced bone loss, and bone metastases all at once.

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The surprising results from the Women's Health Initiative, the largest federally-funded study of women's health conditions, caused many menopausal women to scorn hormone replacement therapy (HRT) and look for other ways to manage their symptoms.

One outcome was an increase in demand for "natural" hormones -- despite questionable scientific evidence that these so-called bioidentical compounds have a better safety profile than their synthetic counterparts.

Now Wyeth -- which makes HRT products Premarin, Premphase, and Prempro -- is petitioning FDA to provide more oversight of bioidentical hormones and crack down on pharmacies that are mass marketing these specialty formulas.

With a doctor's prescription, pharmacists can customize drugs for patients who can't take the standard treatment -- and some have substituted plant-based hormones for the synthetic ones used by Wyeth.

Susan Bishop, director of federal regulatory affairs at the American Pharmaceutical Association, noted that since the practice of pharmacy is regulated by the states, FDA has limited power to regulate compounding.

"We're concerned with Wyeth's petition because it is asking FDA to do something that's not under its authority," she said.

FDA can, however, regulate products that are manufactured in large quantities. But Bishop noted, "It's very difficult to draw a fine line between compounding and manufacturing. That's something FDA has struggled with for a long time."

Wyeth insists that it is not going after the legal practice of compounding, but opposes the mass marketing of bioidentical products as "safer" alternatives to its HRT drugs.

"We need to raise the level of noise," said Ginger Constantine, MD, vice president of women's healthcare and bone repair at Wyeth. "If a woman doesn't know what she's taking, she's potentially at risk."

Wyeth is requesting that FDA enforce provisions of the Food, Drug, and Cosmetic Act (FDCA) that require risk information on labels, package insets, and in advertisements. It is also asking the regulatory agency to issue an FDA Alert or Talk Paper to warn patients and physicians that bioidentical hormones could very well carry the same risks as synthetic estrogens.

"The absence of a warning makes people think it's risk-free," Constantine said.

Michelle Warren, MD, a professor of medicine and obstetrics and gynecology at Columbia University Medical Center, noted there has been a "tremendous" increase in demand for bioidentical HRT -- especially after Suzanne Somers promoted it in a recent book.

As a result of the Women's Health Initiative findings, "there was a lot of fear in the menopausal area," Warren said. "Very often pseudo-science comes to fill the void. The patient has to know that the risks are the same."

Groups such as the International Academy of Compounding Pharmacists (IACP) oppose the company's petition.

Jeffrey Gibbs, an attorney at Hyman, Phelps & McNamara, the firm that represents the IACP, noted that FDA has issued compliance policy guidance on compounding, but never solicited public comment. Therefore, the issue of marketing remains an "open question."

"FDA has been relying on the theory that compounded therapies are new drugs," he said, adding that a federal district court judge in Midland, TX, ruled last month that compounded drugs are not unapproved treatments under the FDCA.

Wyeth's petition lists a number of instances when FDA has sent warning letters to compounding pharmacies. They include: pharmacies that were using active ingredients not approved by FDA, pharmacies that were distributing compounded drugs in large quantities, and pharmacies that were providing samples of compounded drugs to physicians.

But a spokeswoman at FDA confirmed that the agency's purview in this area is uncertain.

"We're still reviewing the comments," she said. "We're going to have to decide which direction to go in."

Increased demand for plant-based hormones has spurred Wyeth to ask FDA to set marketing limits on compounded therapies

Wyeth Petitions FDA on Bioidentical Hormones

The first analyses of drug sales since the implementation of Medicare Part D show an increase in demand for prescription drugs, but also a concerted effort by payers to hold down drug costs.

A study from Wolter Kluwer Health found a three percent growth in the volume of third-party insurance claims after the launch of the prescription drug benefit. Some drug categories, like diabetes, grew six percent in the first 90 days of the benefit's launch.

"You'd anticipate that those are the types of products that elderly patients would utilize -- and they do," said Peter Demogenes, product director in the pharma solutions business unit at Wolters Kluwer.

At the same time, the study also saw a 24 percent increase in claim rejections, the majority of which were due to plan limitations. Drug classes that saw the most rejections for this reason included sleep aids, proton pump inhibitors, and erectile dysfunction treatments.

"Those pharma companies that are proactive and well prepared [are asking themselves]: how much damage potential is my product going to take from cash erosion?" Demogenes noted.

Both payers and pharmacy benefit managers have been recommending less expensive options to customers, including OTC products, and pharmacists have also received incentives for referring patients to preferred drugs and generics.

Therefore, while nearly all drug categories received a boost last quarter, the news was not all positive for individual brands. Being included on a formulary's list of preferred drugs was a strong predictor of how a brand would fare under Part D , according to Mason Tenaglia, managing director of the Amundsen Group, a consulting firm. But generic drugs received the greatest boost overall.

A study from Verispan found that 55 percent of prescriptions filled by Medicare patients were for generic drugs. The analysis also noted that generic manufacturer Teva Pharmaceuticals filled the most prescriptions of any drug maker, and half of the top 10 companies that filled the most prescriptions manufacture generic drugs.

Across the board, drug companies saw an average increase in business of 5.9 percent.

But Tenaglia noted that the impact of Part D on an individual brand is likely to vary from region to region because of the vast differences between Medicare drug plans.

"The national numbers are a bit inconclusive," he said. "Understanding if your brand is doing well or poorly has gotten a lot more complex."

Tenaglia predicted that the market would see increased uptake in drug utilization in the short term, but more price competition shortly thereafter.

Those competitive pressures will spur companies to engage in more rationalization, he added.

"You have to focus your resources in markets where you have access, and selectively reduce resources in markets where you don't," he said.

Drug utilization will also change as beneficiaries hit the so-called donut hole in their coverage and begin to act more like cash payers, Tenaglia added. Because of the number of late enrollees this year, the real impact of the donut hole might not be felt until at least 2007.

Wolter Kluwer's Demogenes also predicts that the plans themselves will become more competitive -- which could impact formularies -- but eventually expects the market to tighten.

"You'll start to see the smaller players weed themselves out," he said. "The strong players are going to survive."

Medicare Part D has increased drug sales and payers are still trying to hold down costs.

Pharmaceutical Executive-06-07-2006

ASCO Showcases Competition Between Big Pharma, Biotech

Wyeth Petitions FDA on Bioidentical Hormones

Medicare Part D Spurs Greater Demand for Generics