—Gil Y. Roth
Editor

One Amgen Center Dr. • Thousand Oaks, CA 91320
Tel: (805) 447-1000
www.amgen.com

Highlights
In 2002, Amgen continued its march toward the Big Pharma ranks, regardless of the fact that its main drugs are biologics. With the acquisition of Immunex and its rheumatoid arthritis drug Enbrel (completed in July 2002), Amgen posted 2002 revenues of $5.5 billion, which would have made it #17 on our Top 20 Pharma list, up from #19 in 2001. If the company’s projections for 2003 hold up, it could leap another two spots on the overall Top Companies chart. And the future looks even brighter for Amgen, with recent drug launches and FDA approval of the company’s Rhode Island manufacturing facility for Enbrel.

Thanks to that clearance, the supply of Enbrel has grown dramatically, enabling Amgen to commence its push to get Enbrel’s annual sales to the $3 billion mark. “Working in close harmony with the FDA, we are delighted to beat our expected timelines and make Enbrel available to patients as quickly as possible,” said Kevin Sharer, Amgen’s chairman and chief executive officer. “The facility is among the most advanced cell culture manufacturing centers in the world and is expected to more than satisfy the expanding patient demand for this unique therapy.”

The 250,000-sq.-ft. structure houses eight 8,000-liter bioreactors and employs more than 550 staffers. “We are proud of our strong heritage in biotechnology manufacturing, and honored to contribute to the well-being of so many patients by making Enbrel available to all who need it,” said Fabrizio Bonanni, senior vice president of quality and compliance. “It has taken a tremendous effort by hundreds of people to complete Amgen’s largest-ever manufacturing facility in record time.”

The company must have been relieved at the news, because a month later it submitted a supplemental Biologics License Application (sBLA) for Enbrel to treat ankylosing spondylitis. Ankylosing spondylitis is a chronic inflammatory disease that affects the spine and results in pain and stiffness, as well as partial or complete fusion of the spine.

That same week, Amgen reported positive results in its Phase III clinical trials of Enbrel as a treatment for moderate to severe plaque psoriasis. The drug is currently indicated only for rheumatoid arthritis. An sBLA for psoriasis would provide a major boost for a drug that’s already growing by leaps and bounds.

The Rhode Island site isn’t the only major construction Amgen’s involved in. The company announced plans in March 2003 to build a biomanufacturing site in Juncos, Puerto Rico. The facilities will include manufacturing for bulk biologics, analytical labs, a syringe line, high-speed packaging, warehouses and administration. Amgen will invest $800 million in the next three to five years on the site, which will employ 600 new staffers, bringing the company’s PR-based staff to 1,000.

For most biopharma companies, the good news about Enbrel and the new manufacturing sites would be enough for a year. But Amgen has larger designs on the healthcare industry. In April 2002, the company launched Neulasta, a treatment to decrease incidence of infection in some chemotherapy patients. The drug was also approved by the EU in August 2002, and began rolling out in Europe in January 2003. Worldwide sales of the drug were $464 million in 2002, and reached $258 million in the first quarter of 2003.

In July 2002, the FDA approved Aranesp for chemotherapy-induced anemia in patients with nonmyeloid malignancies. Aranesp is a recombinant protein that stimulates production of oxygen-carrying red blood cells and requires fewer injections than existing treatment. Less-frequent dosing results in fewer injections for patients, which improves quality of life. Clinical studies showed that patients suffering from chemotherapy-related anemia who received Aranesp consistently reached target hemoglobin (red blood cell) levels. The studies showed Aranesp to be generally well-tolerated. “Aranesp is an important development that will make it easier for oncologists to treat their chemotherapy patients’ anemia,” said Mr. Sharer. “Joining the once-per-chemotherapy-cycle dosed Neulasta, Aranesp’s simplified dosing regimen represents Amgen’s next generation of powerful supportive care treatments for patients receiving chemotherapy.” Aranesp was approved by the FDA in September 2001 for the treatment of anemia associated with chronic renal failure, also known as chronic kidney disease, for patients on dialysis and patients not on dialysis.

With the increased labeling, Aranesp posted sales of $255 million in the first quarter of 2003. Enbrel increased first quarter 2003 sales to $274 million, and Amgen projects its sales will hit $1.2-1.4 billion this year. Could the company place five drugs in the billion-dollar category by the end of 2003?

Replenishing the supply of blockbusters would be a good thing for Amgen, as the FDA has talked more in recent months about establishing guidelines for biogenerics. This could eventually threaten Amgen’s long-standing franchise drugs, increasing the need for newer billion-dollar products from the biopharma kingpin.

Amgen’s position was improved in October 2002, when the company received a favorable ruling from an arbitrator who concluded that Johnson & Johnson breached its license agreement with Amgen by promoting its brand of Epoetin alfa, Procrit, into Amgen’s reserved dialysis market. As a result, Amgen was awarded $150 million in damages. The arbitrator found that Johnson & Johnson’s conduct was “illegal, egregious, and indefensible,” according to an Amgen statement. Amgen executives seemed to hope that the arbitrator would void the agreement between the companies, which would have created a much bigger market for Amgen’s Epogen brand of Epoetin alfa.

Also in October 2002, Amgen filed a supplemental Biologics License Application (sBLA) with the FDA for the use of Kineret to inhibit the progression of structural damage in adult patients with moderately to severely active rheumatoid arthritis (RA). Kineret is currently indicated for the reduction in signs and symptoms of moderately to severely active RA in patients 18 years of age or older who have failed one or more disease modifying antirheumatic drugs (DMARDs).

The sBLA is based on the results of a 12-month, double blind, placebo controlled trial. Dr. Pirow Bekker, Amgen’s senior director of clinical research, commented, “In a one-year study, we found that more patients treated with Kineret had no progression in bone erosions or cartilage degradation than patients treated with placebo. We also saw that the effect of Kineret was evident early, with significant inhibition of disease progression apparent by week 24.”

Amgen is planning to submit its first NDA for Cinacalcet HCl, a small-molecule drug to treat secondary hyperparathyroidism. The drug was licensed from NPS Pharmaceuticals and ties in with the company’s expertise in renal care.

In May 2003, the company took additional steps to develop its pipeline by collaborating with Tularik on discovery and development of oncology drugs. The terms of the collaboration include milestone payments of as much as $21 million per target, $50 million in committed research funding during a five-year period and royalties on net commercial sales of products resulting from the collaboration. Amgen will retain exclusive worldwide commercialization rights to products resulting from the collaboration, while Tularik will have an option to some co-promotion rights in the U.S. on a product-by-product basis. Amgen also bought a 21% stake in Tularik.

“Tularik and Amgen share a common approach to drug discovery and development,” said Roger M. Perlmutter, M.D., Ph.D., Amgen’s executive vice president, R&D. “Tularik has built a high quality discovery engine that adds substantially to our own broad-based research capabilities. We expect this collaboration will result in a set of high potential clinical programs and, we believe, new therapies that will improve patients’ lives.”

With several drugs heading for blockbuster status, a growing internal pipeline, and a solid in-licensing program, Amgen looks like it’s not giving up the #1 spot in the Top Biopharma list any year soon.

1 DNA Way • South San Francisco, CA 94080
Tel: (650) 225-1000
www.gene.com

Highlights
Genentech was the first company to market a biotech medicine (recombinant human insulin), kicking off the first of several bio-stampedes for investors. It triggered another one in May of this year when it announced that a Phase III trial of its Avastin drug, plus chemotherapy, extended the lives of metastatic colorectal cancer patients by approximately five months. The trial also met its secondary endpoints of progression-free survival, response rate, and duration of response.

Avastin is a monoclonal antibody that inhibits Vascular Endothelial Growth Factor (VEGF), a protein that plays a critical role in tumor angiogenesis (the formation of new blood vessels to the tumor) and maintenance of existing tumor blood vessels. By inhibiting VEGF, Avastin is designed to interfere with processes that are critical to tumor growth and metastasis. In September 2002, the company declared that an Avastin trial to treat relapsed metastatic breast cancer was a failure, so the drug’s amazing success in the colorectal cancer trial hit the industry like a shockwave.

“The data from this important Phase III trial, which show that treatment with Avastin and chemotherapy resulted in improved survival, highlights a potentially new way to treat patients with metastatic colorectal cancer,” said Susan D. Hellmann, M.D., M.P.H., Genentech’s executive vice president, development and product operations, and chief medical officer. Genentech plans to try Avastin to treat renal cell carcinoma.

Despite the great news, FDA approval for Avastin is still a ways off. The company is still organizing the Phase III data and has yet to file a BLA for the product, although the FDA has given the drug Fast Track designation.

But that’s alright because Genentech has finally heard from the FDA with approval for asthma treatment Xolair. This comes as great relief for Genentech (and partners Novartis and Tanox), which had to refile the drug after the FDA denied the previous application, pending additional trial data and ADME/T information.

In May 2003, an FDA advisory committee unanimously recommended approval of Xolair for treatment of moderate-to-severe allergic asthma in adults and adolescents. The Xolair BLA was filed a few days before the company (along with XOMA) filed a BLA for Raptiva, a treatment for moderate to severe plaque psoriasis.

During 2002, Genentech moved rhuFab V2 into Phase III trials for age-related macular degeneration. RhuFab V2 is another VEGF-inhibitor, a class of drugs the company is pursuing hotly.

The company has also continued to develop its pipeline through collaborations. In June 2003, Genentech signed new deals with Biogen and Idec. The Biogen agreement is an R&D collaboration for a BR3 (BAFF-R) protein therapeutic currently in Biogen’s pipeline. The protein is a B-cell activating factor receptor of the TNF family and is a key target for developing drugs to treat disorders associated with abnormal B-lymphocyte activity, such as rheumatoid arthritis and lupus.

“We look forward to working with Biogen on BR3, a target of potentially great importance in the area of autoimmune disease,” said Richard Scheller, Ph.D., Genentech’s senior vice president, research. “Genentech and Biogen are leaders in advancing the understanding and treatment of autoimmune disorders and are entering into this collaboration to promote scientific progress in this area.”

The IDEC collaboration is designed to develop one or more new humanized anti-CD20 antibodies targeting B-cell disorders for a broad range of indications. Genentech and Idec plan to file an IND on their first humanized anti-CD20 antibody by the end of this year. The companies will work together to develop and commercialize additional anti-CD20 products that are targeted for specific patient populations, depending on the severity of their B-cell disorder. The primary focus of this collaboration will be to develop and launch a humanized anti-CD20 molecule while evaluating the utility for more efficacious follow-on humanized molecules. The first time these companies worked together, they yielded Rituxan, an anti-CD20 antibody that’s yielded billions in revenues.

Filings, approvals and alliances are crucial to the company’s “5×5 goals,” a series of achievements the company plans to reach by 2005. Implemented in 1999, the 5×5 goals include:

        1) 25% average annual increase in pro forma earnings per share;

        2) 25% pro forma net income as a percentage of revenues;

        3) Five new products and/or indications approved;

        4) Five significant products in late-stage clinical trials; and

        5) $500 million in new revenues from strategic alliances or acquisitions.

How are they doing on these goals? According to the company, here’s where they stood at the end of 2002:

1) 27% EPS growth (although I always keep a decent-sized grain of salt on hand when presented with pro forma results), with projections of 25% on average for the full 1999-2005 span;

2) 18% on #2, due to profit-sharing restrictions from the Rituxan agreements with Idec and parent company Roche;

3) Approvals for three products and one delivery device (Nutropin AQ Pen), with two potential approvals awaiting in 2003 (including Xolair);

4) “We should exceed this goal,” according to a company statement, “due to the strength of our research organization, in-licensing activities and early-stage pipeline”;

5) No fixed number from the company, which did point out that it has entered 25 significant alliances since 1999, including marketing agreements in Europe and Asia for Raptiva.

In a March 2003 analyst meeting, Genentech’s chairman and chief executive officer Arthur D. Levinson, Ph.D., remarked, “We are committed to delivering on our long-term growth strategy and anticipate a significant growth period ahead. We expect 2003 to be an especially exciting year for Genentech, with anticipated FDA licensing decisions on Xolair and Raptiva, and data from two important Phase III oncology clinical trials.”

When it’s an exciting year for Genentech, it’s an exciting year for biopharma.

Chemin des Mines 5bis • PO Box 54
1211 Geneva 20 • Switzerland
Tel: (41) 22 739 3000 • www.serono.com

Highlights
Serono’s traditional source of revenues, reproductive health products, grew more than 8% in 2002, to $622 million. Sales of Gonal-F increased by 9.7% to $450 million. In recent years, Serono has been phasing out its urine-derived products in favor of recombinant proteins, which provide a superior products and high purity. Recombinant products now account for nearly 90% of the company’s gonadotropin sales in the U.S. and Europe.

However, the company’s big news was the performance of its MS drug, Rebif. In 2002, Rebif became the company’s top-selling product, passing Gonal-F. Those sales are only going to rise, especially after Serono’s July 2002 co-marketing agreement with Pfizer for Rebif in the U.S. market. Pfizer paid Rebif an upfront fee of $200 million in the deal, will share all commercialization and development costs in the U.S., and will receive a payment based on Rebif sales in the U.S. Serono will record all sales and continue to distribute the product in the U.S.

“We are delighted to work with Pfizer as our marketing partner for Rebif in the U.S.,” said Ernesto Bertarelli, chief executive officer of Serono. “The combined strengths of our companies will enable us to build on the strong momentum Rebif has achieved since its launch, and to accelerate the market penetration of Rebif in the U.S.”

Clearly, both sides believe the added marketing push of Pfizer will be enough to push Rebif past Biogen’s Avonex, the top drug in the MS market. But, given Pfizer’s recent propensity for acquiring its co-marketing partners (see Warner-Lambert (Lipitor) and Pharmacia (Celebrex/Bextra)), are we looking at another potential takeover target?

Serono and Biogen aren’t only fighting over their MS drugs (Rebif and Avonex). It looks like the companies are ready to square off in another arena. After Serono licensed the rights to Genentech’s psoriasis drug Raptiva outside the U.S. and Japan, it positioned itself against Biogen in that market, where Raptiva will compete with Biogen’s recently approved Amevive. Both companies are also working on getting their drugs approved for rheumatoid arthritis. Hard to believe that companies would go to such lengths to stay ahead of each other on the Contract Pharma Top Biopharma list.

Serono extended its possible MS franchise by licensing the U.S. market for Novantrone from Amgen in November 2002. Novantrone was approved for MS by Immunex in 2000, and was an “odd drug out” when Amgen acquired the company in 2002. Novantrone had $71 million in U.S. sales in 2001.

The company entered several other licensing deals and collaborations last year. In July 2002, AstraZeneca licensed to Serono the rights to develop and market anastrozole (Phase II), an aromatase inhibitor, for female infertility. In October 2002 IVAX and Serono agreed to develop and market cladribine (preclinical), a potential oral therapy for MS. In addition, following the positive outcome of a Phase III clinical trial of Serostim in short bowel syndrome, Serono filed a regulatory submission to expand the drug’s indications in the fourth quarter of 2002.

Serono appears poised to make a revenue push in 2003 and beyond, with co-marketing deals, in-licensing, and an advancing pipeline. It’s unclear if there’s enough growth potential in Rebif and Raptiva to get Serono into range of Genentech, but the company should be able to stay ahead of Biogen for another year.

Highlights
Biogen’s days of being a one-trick pony are nearly behind it. Not only has Amevive, its psoriasis treatment gotten the go-ahead from the FDA, but it has joined forces with a key biotech player. The company recently accepted a stock-for-stock merger offer from IDEC Pharmaceuticals valued at $6.4 billion. It is the largest biotech deal this year and the second largest biotech deal in history, just behind Amgen’s purchase of Immunex for $10 billion in 2001. The combined company will be called Biogen Idec, Inc.

According to a company statement, Idec has a strong franchise in cancer and a growing focus on autoimmune diseases, while Biogen is strong in the autoimmune area and is increasingly developing capabilities in cancer. Analysts say, however, that the merger is not necessarily the remedy for two companies facing declining sales growth of their most successful drugs. Patrick Flanigan, an analyst at Adams Harkness & Hill told Investor’s Business Daily, “It was never clear to me that combining two companies with somewhat mediocre fundamentals creates one company with superior fundamentals.”

Neither company’s pipeline is overflowing. Biogen’s Antegren, a possible treatment for MS and Crohn’s, is currently in Phase III studies and Idec’s Rituxan is in late stage studies for the added indication of rheumatoid arthritis and other autoimmune disorders.

Others see the merger as one of the best moves Biogen could make. Adam Feuerstein, a columnist for RealMoney.com told TheStreet.com, “When you combine these companies, you get larger scale, less dependence on a single marketed product, more diversification and less risk from any individual pipeline project; all solid reasons for a merger, but not exactly sexy reasons. But then, does every deal have to be sexy?”

Two of the rumored reasons for the merger were cost cutting and sheer size. There was no one drug that either company was after. Idec president and chief operating officer commented to Investor’s Business Daily, “What we’d like to become, we each get. The rationale for combination of the companies is pretty simple. It’s really about generating critical mass. Size does matter in the biotech sector.” He also stated that the merger will help the two companies steer clear of $300 million in costs between now and 2007. Idec will also benefit from the manufacturing infrastructure already in place at Biogen and will not need to build new facilities. That manufacturing structure also makes the new entity attractive to smaller biotechs needing to partner up with a larger organization to manufacture its product.

Some of that manufacturing infrastructure is being taken up by Biogen’s newest member of its drug family. In January 2003, the company received FDA approval for Amevive, a drug indicated for the treatment of adult patients with moderate-to-severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy. Psoriasis is an autoimmune skin disease in which skin cells multiply 10 times faster than the normal rate. The excess cells pile up on the skin’s surface, forming red, raised, scaly plaques that can be painful and disfiguring. Psoriasis affects about 80 million people worldwide and 4.5 million U.S. adults. Approximately 1.5 million U.S. psoriasis patients suffer from moderate-to-severe disease. Kenneth Gordon, M.D., Department of Dermatology, Northwestern University, and Amevive clinical investigator, said, “Amevive is unique because it seems to have a long-lasting effect. In our clinical trials, patients took the medication for 12 weeks and then stopped treatment for several months. During this time off treatment, many of our patients had prolonged remission of their disease. A number of my patients have told me that Amevive has made a real difference in their lives, giving them more confidence and allowing them to enjoy their favorite activities again.”

Amevive’s approval was a long time coming, and Biogen is resting on its laurels. James Mullen, Biogen’s chief executive officer, recently told Businessweek.com, “We went seven years between our first and second major product launch. Obviously, that’s longer than we would have liked. But we’ve built a strong commercial infrastructure, and we’ve carried forward several products in the pipeline.”

He added, “Amevive is the first product out of the pipeline since Avonex. It represents a nice victory for us, because it’s a completely home-grown product that emerged from our labs in the late 1980s.” Although Amevive is the first new therapy indicated specifically for the treatment of psoriasis, drugs from Genentech (Raptiva), Johnson & Johnson (Remicade) and Abbott Labs (Humira) are breathing down its neck and are in the last stages of development.

Competition is nothing new to Biogen. Avonex, the company’s blockbuster drug (and only drug, for that matter) has faced stiff competition from Serono’s competing MS drug, Rebif. In the past year, the companies have gone back and forth, claiming its drug is better. Each has taken turns filing with the FDA for label changes and showering new clinical information on the agency to support their claims. The most recent change came in May of 2003, when the FDA approved a label change for Rebif to include an update that uses data from a study that directly compared the two therapies. The 677-patient study showed that Rebif patients were more likely to remain free of relapses after 24 and 48 weeks than were patients on Avonex. In March of 2002, Biogen had asked the FDA to prevent Serono from stating that Rebif was better than Avonex. Sales growth for Avonex has declined in the last year.

Although it may seem as if Serono has won the battle, the war rages on. Biogen tinkered with Avonex’s delivery system to improve compliance and convenience, securing approval of a prefilled syringe in late May 2003. The new prefilled syringe was designed to make treatment more convenient for people with MS. As with the current formulation of Avonex, the new one will be indicated to slow the progression of disability and reduce the frequency of relapses in relapsing forms of MS, including people who have experienced a first clinical episode and who have brain scans consistent with MS. Until now, standard practice has been to treat MS only after a patient experiences at least two clinical events.

Biogen’s one-product days have finally come to an end, though competition continues to follow closely at its heels. The company is trying to stay one step ahead of the pack by tweaking its existing therapy, while trying to grab market share for its newest drug. The combined entity of Biogen Idec, Inc. should also put the company on firmer ground, netting revenues from more than one blockbuster drug as well as attractive prospects waiting in the wings. But only time will tell if bigger really is better.

One Kendall Sq. • Cambridge, MA 02139
Tel: (617) 252-7500 • Fax: (617) 252-7600
www.genzyme.com

Highlights
Genzyme General’s pipeline is finally paying off. After last year’s Renagel overstocking fiasco, the company has seen its fair share of good news.

The company’s collaboration with BioMarin Pharmaceutical has paid off with the FDA approval of Aldurazyme. It is the first specific treatment for people with the rare genetic disease mucopolysaccharidosis I (MPS I). Aldurazyme was developed by BioMarin and Genzyme under a joint venture agreement that assigns commercial manufacturing responsibilities to BioMarin, and worldwide sales and marketing responsibilities to Genzyme. The company’s marketing strategy in the past, with Cerezyme (a treatment for Gaucher disease), involves contacting those medical professionals who would specifically come in contact with those patients with specific disorders and abnormalities. The company also secured EU marketing approval for Aldurazyme in June 2003.

Genzyme has begun to market Aldurazyme to physicians through an expanded sales force of nearly 40 professionals who specialize in providing enzyme replacement therapies for rare genetic diseases. Sales efforts will focus on raising awareness of MPS I and the availability of Aldurazyme among geneticists, pediatricians and sub-specialists who are involved in the multi-disciplinary care of patients with MPS I. Clinical trials have demonstrated that Aldurazyme can provide clinically important benefits for patients, including improved pulmonary function and walking ability. Aldurazyme has also been shown to be effective at reducing the excess carbohydrates that are stored in the organs of patients with MPS I, providing evidence that the enzyme is effective at a biochemical level. Aldurazyme has not been evaluated for effects on the central nervous system manifestations of the disorder. As the first drug ever approved for MPS I, Aldurazyme has been granted Orphan Drug status in the U.S., which confers seven years of market exclusivity. Although the possible patient population for MPS I is small (3,000 people are known to suffer from MPS I), the drug costs $170,000 for a year of treatment and the company expects to make $9 million in sales for 2003.

In other approval news, the FDA has approved Fabrazyme, an enzyme replacement therapy for Fabry disease. Fabrazyme is the first treatment approved in the U.S. for people suffering from Fabry disease, a rare and potentially fatal inherited disorder. Robert J. Desnick, M.D., Ph.D., professor and chairman of human genetics at Mount Sinai School of Medicine, commented, “FDA approval of Fabrazyme is a culmination of more than 30 years of research on enzyme replacement therapy for Fabry disease.” Fabrazyme has also received Orphan Drug designation. Fabry disease affects approximately 5,000 people worldwide. The average lifespan of patients with the disease is 50 years. The disease is caused by a deficiency of
the enzyme alpha-galactosidase A, which leads to the progressive accumulation of lipids––primarily globotriaos-lyceramide (GL-3)––within cells of the kidneys, heart, and other organs. Clinical manifestations of the disease include renal failure, stroke, heart disease and debilitating pain. The accumulation of GL-3 in renal endothelial cells is thought to play an important role in renal failure. A year’s worth of treatment on Fabryzyme costs $170,000-$180,000 a year and the company expects to take in $78 million this year. This type of targeting a small population of patients has worked in the past for the company, proving that you don’t need a blockbuster to survive.

In the pipeline, Genzyme Molecular Oncology achieved positive findings from the completion of one of its cancer vaccine studies in melanoma. The Phase I/II trial was the first one of its kind to have utilized two melanoma antigens included in adenovirus vectors in a single vaccine. Frank G. Haluska, M.D., Ph.D., of the Massachusetts General Hospital and Dana-Farber Partners Cancer Care, is the lead investigator of this multicenter vaccine study. “The clinical and immunologic response data from this trial are encouraging,” stated Dr. Haluska. “With one patient sustaining a complete response for more than a year and a half, and another two patients demonstrating either a partial response or stable disease, this study provides good reason for optimism that this vaccine approach could prove to be effective in treating melanoma.”

The approach used in the clinical trial involved two common viral vectors modified to express melanoma-specific proteins, or antigens. These vectors were introduced to the patient’s immune-stimulating dendritic cells ex vivo in a cell processing facility, and then injected back into the patient under the skin in a series of as many as six vaccinations. The intent of this strategy is to spark the patient’s immune system and direct it to attack cancer cells displaying either of the two melanoma antigens. The trial enrolled patients with locally advanced or metastatic melanoma, the majority of whom had received prior treatments for their disease. Of the 27 patients enrolled in the study, 21 were evaluable for response assessment.

In a move to consolidate its corporate structure, Genzyme General is incorporating Genzyme Molecular Oncology and Genzyme Biosurgery into one entity and will do away with the tracking stocks for those units. At the same time, the company broadens its portfolio with possible winners like the above mentioned vaccine, as well as Synvisc from Genzyme Biosurgery, an injectable therapy indicated to ease pain resulting from osteoarthritis of the knee. The company hopes use the drug to alleviate pain from osteoarthritis of the hip as well. Sales for 2002 were $90 million.

The company has been able to stay near the top for the last few years based on drugs that treat a small number of patients, but analysts are wondering if that strategy will be able to keep it going in the years ahead.