Breast cancer affects more than 1 million women worldwide, and will kill approximately one-third of patients each year. There are many drugs marketed to treat breast cancer, and competition is fierce. It is a highly active area of research, as there is still such a high unmet need. As a result, over a dozen new pharmaceuticals are expected to enter the market over the next 8 years. The challenge facing companies already in the market, is how to maintain the revenues generated by their products, in light of increasing competition.
To maintain a healthy product life-cycle, product development needs to continue post-launch. These strategies can help maintain sales, so when the product reaches maturity, it helps combat the negative influence of new drugs and generic companies. Two strategies suggested in this article are licence extensions in to the earlier treatment of breast cancer, and the development of new formulations of existing drugs
Reducing Toxicity There has been a trend in Europe toward therapies that allow the patient to have a better quality of life whilst maintaining efficacy. This is provided by the hormonal therapies, such as tamoxifen and the aromatase inhibitors, and as a result , women who are suitable for hormonal therapy will be offered hormonals in preference to cytotoxic treatment. There are, of course, patients who are not suitable for hormonals, and will be given chemotherapeutics.
There are high levels of toxicity associated with the use of chemotherapeutics, which can result in patients not only suffering terrible side effects but also refusing medication. It is often believed that to put a patient onto a course of cytotoxic drugs is simply delaying the inevitable at a huge cost to the patient's quality of life.
To combat the high toxicity of these products, increasing uptake and patient compliance, there has been a drive towards developing coated drugs. They facilitate a more targeted delivery of drugs towards the site of the tumour, causing less impact on healthy cells and therefore, fewer side effects. Encapsulation technologies are an important advancement in drug delivery technology, but have yet to make their mark on the marketplace for breast cancer pharmaceuticals.
Liposomal doxorubicin, marketed as Myocet (Elan) and Caelyx (Schering-Plough; marketed as Doxil in the US), are available in Europe, for the treatment of breast cancer, but their success has been limited. It is has been suggested that it is due to the higher cost of the new formulations in comparison to conventional treatment. Oncologists feel that they do not provide enough benefits over the conventional composition to warrant the increased price. The niche for liposomal formulations may be in the treatment of patients who are in poor general health or are prone to cardiotoxicity, due to the reduction in side effects.
A number of companies have liposomal formulations in the pipeline, such as:
Toscosol by Sonus Pharmaceuticals. A new formulation of paclitaxel that uses a vitamin E suspension, which is thought to be faster to administer, has fewer side effects and better efficacy. This product has positive phase II trial results.
NeoPharm is developing liposomal encapsulated paclitaxel (LEP) and liposomal encapsulated doxorubicin, which are in phase II trials. There may some delay with these products as NeoPharm has been involved with legal wranglings with its former partner in these products, Pharmacia.
Annamycin, a liposomal anthracycline from Antigenics, which is in phase II trials for refractory breast cancer, initiated in spring 2000. It involves patients who overexpress p-glycoprotein, which is responsible for exporting drugs out of cells, resulting in resistance.
DaunoXome (liposomal daunorubicin) by Gilead, already licensed for Kaposi's sarcoma, is in trials investigating use in metastatic breast cancer.
These products hold great potential if the oncologists and purchasers can be convinced of their benefits. Their market penetration could significantly increase, as they have the potential to replace the uncoated versions. The new formulations also increase the potential of the drugs as generic manufacturers find them unattractive, as the technology is expensive. Patient Compliance
Oncology is still one of the few areas of medicine where the most common route of drug administration is through the IV route. Several oral drugs have emerged in recent years, with the launch of Xeloda (capecitabine from Roche) heralding the latest breakthrough in breast cancer. Patient preferences for oral delivery have been cited, with statistics showing that over 80 percent of patients prefer this route of administration. The main reason given by patients is the convenience of being treated at home rather than in a hospital setting. It also allows the patient to feel they have much more control over their therapy.
Many oral products are reformulations of older drugs, which are sold at a low price due to the level of generic competition. For example, cyclophosphamide has been given orally for many years in women with breast cancer as part of some CMF regimens. This strategy is of benefit to the developer as the increased patient compliance attracts an increased price and, as with the liposomal formulations, generic companies find the oral formulations unattractive due to the cost of manufacturing.
An essential strategy in lifecycle extension of oncology products is the expansion of the licensed indication. Often when a product is initially granted approval in breast cancer, it is for the treatment for metastatic disease, in second or third line. The patient numbers here are small, which restricts revenues. Additionally, there can be more competition later in treatment paths, as there is little consensus on how to treat these patients most effectively. A solution for this is to carry out trials in a first line setting, to show the drug's efficacy in early disease management. The patient numbers here are far larger, therefore, so are the potential revenues.
AstraZeneca has adopted this strategy in the lifecycle management of its aromatase inhibitor, Arimidex (anastrozle). It was initially licensed for second line therapy, which was extended to first line. In November 2002, Arimidex was licensed for the adjuvant treatment of hormone receptor positive breast cancer, where tamoxifen is unsuitable. It is anticipated that the rest of Europe will follow suit by 2004, through the mutual recognition system. This strengthens AstraZeneca's position in the market, as Arimidex is the first aromatase inhibitor with this indication. The other aromatase inhibitors Femara (Novartis) and Aromasin (Pharmacia) are not expected to be licensed for this indication until 2005 and 2006, respectively. The potential revenues are greatly increased by the extension. It is anticipated that the aromatase inhibitor will eventually replace tamoxifen in the adjuvant setting.
The goal for pharmaceutical companies is to extend the lifecycle of its products for as long as possible, to gain maximum revenues. The main strategies adopted by the firms involved in breast cancer therapy are new formulations and licence extensions. This puts the product in a stronger position to face the increasing competition from new therapies and generic companies, as the drug reaches maturity.
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Last updated on: 27/08/2010
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