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Breathing new life

Innovative life cycle management can make mature products profitable for pharma

missing image fileMarketing drugs in their later life-stages can be a challenge, especially in the current competitive market place.

However, by using innovative life cycle management strategies, pharmaceutical companies may be able to extend drug use into new indications and markets to preserve or extend the value of a particular brand.

For example a cancer drug that shows efficacy in a range of tumour types or in combination with existing treatments can find new business well into its life cycle.

Rapidly growing emerging economies also represent a new customer in the pharmaceutical market, and could fuel sales of products that would otherwise be in the declining stages of their life.

An example of a brand that has been able to expand sales utilising this strategy is the oral chemotherapy drug, Xeloda (capecitabine). Xeloda has been a staple of Roche's oncology franchise for nearly a decade, during a time period when niche technologies stole much of the spotlight.

Many brands would start to reach maturity or even exhibit declining sales during this stage. However, through a mix of expanding indications and reaching out to new markets, Roche has seen Xeloda's sales move steadily forward.

Xeloda was introduced into the US market in 1998 as monotherapy for advanced breast cancer in patients whose cancer is resistant to other types of chemotherapy, such as paclitaxel and anthracyclines. Originally, Roche thought the breast cancer indication would be used only as an entry strategy for Xeloda into a broader oncology market, particularly in colorectal cancer.

When administered as a monotherapy Xeloda does not cause hair loss in patients and Roche believed that the absence of this distressing side effect meant that the drug could move quickly to market in the breast cancer sector.

Roche was looking to colorectal oncology because, unlike breast cancer, which has a fragmented and competitive market, there were fewer therapies for colorectal cancer and a high unmet medical need.

Xeloda was perceived as better than the standard colorectal cancer treatment, intravenous 5-FU chemotherapy, but it had demonstrated only limited use in adjuvant breast cancer patients. However, in 2000, Roche received a welcome surprise. Clinical trial results of metastatic breast cancer patients showed a survival advantage of three months for patients taking Xeloda in combination with Taxotere (docetaxel) versus Taxotere alone. Roche adapted its strategy in light of this information.

Once a survival advantage was shown for Xeloda in combination with Taxotere, the thinking changed. There are very few products that have shown a survival advantage in breast cancer, said Roche life cycle leader, Jonathan Dickinson. It was at this point that we realised Xeloda had a future as a combination drug in the adjuvant breast cancer setting, and that the breast cancer indication overall could be as important as colorectal cancer.

Combination approval

Roche received US approval for the Xeloda/Taxotere combination in 2001, the same year the company received US and EU approval for Xeloda monotherapy in metastatic colorectal cancer. Most cancer treatment was moving towards combination therapies at that time.

As a result, based on the Taxotere results, as well as early combination trials in colorectal cancer, Roche made a strategic decision to widen the Xeloda marketing strategy to encompass the broader gastrointestinal market, as well as breast cancer. To set this strategy in motion, the company invested in new combination registration studies. Roche has ongoing clinical trials of Xeloda in combination with a number of drugs including oxaliplatin, irinotecan Avastin, and Herceptin.

We could target other tumour types such as liver, head and neck and lung, but we believe the right strategy at this time is for Xeloda to focus on these two key indications, said Dickinson. By staying focused on gastrointestinal and breast cancers, we support sales by correct positioning and can provide support to clinicians about which patients are most likely to benefit.

In 2005, Roche received US and EU approval for Xeloda monotherapy in adjuvant colon cancer. The firm applied for label extensions in the US and the EU to broaden the registered indication of Xeloda for the treatment of metastatic colorectal cancer in combination with Xelox (capecitabine plus oxaliplatin), and Avastin.

Earlier this year, Roche was granted a first line licence for the use of Xeloda in metastatic gastric cancer in combination with platinum-based chemotherapy. In the future, Roche plans to file Xeloda for in adjuvant breast and colon cancer in different combinations (see boxes 1 and 2).

Even with strong efficacy results, marketing a product that is a long way into its life cycle can still be challenging. One of Roche's key marketing goals is to ensure that the positioning it takes up in prescribers' minds reflects the qualities and potential of the treatment.

Xeloda has a unique mode of action; it targets the enzyme Thymidine Phosphorylase (TP), which is more common in cancer cells than in normal, healthy cells. In the cancer cells, Xeloda comes into contact with TP and is converted into the cancer-killing agent, 5-FU.

Because Xeloda is converted to 5-FU mainly in the cancer cells rather than in healthy cells, patients tend to experience fewer of the common side effects that are associated with iv chemotherapy, such as nausea, vomiting and low white blood cell counts. And because it is in tablet form, Xeloda is more convenient for patients to take at home.

Maximising the benefits of Xeloda's mode of action required a two-pronged marketing strategy. For the physician audience, efficacy is paramount. Roche concentrated all of its physician marketing materials on Xeloda's progression-free and overall survival data, and spent very little energy promoting its superior side effects profile.

The side effects profile does resonate well with nurses and patients who both care about a medication's tolerability. The mode of action can be used to explain the rationale for why Xeloda has fewer side effects. For that reason, Roche develops all of its consumer marketing materials focusing on efficacy plus freedom. The company chose the word 'freedom' to symbolise the favourable side effects profile and the flexibility that tablets offer over iv infusion.

Less side effects, the flexibility and simplicity of having a tablet lessen the time the patient needs to be in hospital by a considerable number of hours compared to intravenous treatment; these are things that resonate very well with that audience, explained Dickinson.

Opportunities worldwide

Global expansion can also provide new opportunities for products that have been on the market for several years. Xeloda is currently licensed in more than 100 countries worldwide, including the EU, the US, Japan, Australia and Canada, and Roche say it has now been used to treat 1.4 million patients.

In the established markets, increasing sales are being driven with new indications and survival data. However, Xeloda is also seeing double-digit sales growth in the emerging economies of Asia and
Latin America.

We've seen a lot of expansion in the Asian market, particularly in China which is a very important market for Xeloda moving into the future. We are also seeing very high sales in countries like Mexico, Dickinson said. Because Xeloda is taken orally at home, patients do not have to travel to treatment centres as frequently. This is important in those countries where distances are often great. In addition the treatment centres do not always have the infrastructure (capacity) to support iv chemotherapy.

Another challenge when a drug holds potential across a number of indications, is to ensure that resources are invested in the most fruitful directions. We have to predict where our investment is most likely to reap rewards, he said.

So we started our original studies in the prime indications that have biggest business opportunity and then worked towards consideration of the smaller tumour types and made assessments here in conjunction with the unmet medical need.

Mature products can still be profitable for pharma companies. As manufacturing processes are perfected and economies of scale increase, profit margins improve.

There has been an element of luck in the success story of Xeloda but mostly it has come down to a strong brand image and clever life cycle management, concluded Dickinson.

The Author: Nerea Hinzpeter is senior account manager at ShireHealthPR in New York

Rapidly growing emerging economies also represent a new customer in the pharma market and can fuel sales

Box 1: Xeloda EU licence history

Metastatic colorectal cancer
Monotherapy first line


Metastatic breast cancer
first line in combination with docetaxel


Adjuvant colon cancer


Metastatic gastric cancer
In combination with platinum-based chemotherapy first line


Metastatic colorectal cancer
Combination with oxaliplatin + Avastin

First and second line submitted
for approval in 2007

Box 2: Xeloda EU future filings

Adjuvant colon cancer in combination with oxaliplatin


Adjuvant breast cancer in combination with docetaxel


Adjuvant colon cancer in combination with oxaliplatin + Avastin


Even with strong efficacy results, marketing a product that is a long way into its life cycle can still be challenging

5th November 2007


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