These include drugs to treat cancer, venous thrombosis, gastrointestinal disorders and hospital acquired infections. Alongside these and falling in the same therapeutic categories are drugs that have come off patent in the USA since 2004 and have attracted generic competition, such as cancer therapies carboplatin and paclitaxel.

Generic companies are also beginning to take an interest in some of the older high value biopharmaceuticals, including erythropoietin, filgrastim, recombinant insulin, somatropin and interferon. If regulatory hurdles can be overcome, the potential rewards for generic companies in biosimilar products are huge. This sector is still very new; to date, only two companies have successfully followed the regulatory path in Europe and it is proving even more difficult to attain regulatory approval for biosimilars in the US.

The traditional view of generic drugs is that they offer a cheap alternative to their branded equivalents. Cost has been an important factor in their development, particularly for oral drugs that are relatively cheap to produce and can be introduced to that market at a fraction of the price of the original drug. Generic companies are, however, beginning to look for higher profit margins and injectable drugs potentially offer such opportunities.

Combined branded and generic sales of the non-biological injectables included in this study were around US$20.5 billion in 2005, of which around US$12.0 billion will lose patent protection in the US by 2010. The proprietary biopharmaceuticals that we believe are most likely to become available as generics once the legal hurdles to registration have been overcome, currently have combined sales in the region of US$27.2 billion.

Companies analysed in this report
Abraxis Pharmaceutical Products
Amphastar Pharmaceuticals
Apotex
Baxter Healthcare
Bedford Laboratories
Hospira
Mayne Pharma
Orchid Healthcare
Paddock Laboratories
Sandoz
Spectrum Pharmaceuticals
Sun Pharmaceutical Industries
Teva Pharmaceutical Industries Cancer
Cancer is a leading cause of morbidity and mortality in the developed world and is increasing in the developing world. In Western Europe, 25.4% of all deaths are attributed to cancer. In the Americas, around 18.4% of registered deaths are due to cancer; in the USA the proportion is 22.8% (2003). In 2006, around 1.4 million people in the USA will be diagnosed with cancer and an estimated 564,830 will die from the disease. Of these, 16.7% will be diagnosed with prostate cancer, 15.3% with breast cancer, 12.5% with cancer of the bronchus and lung, and 10.6% with colorectal cancer.

The available treatment options for cancer may vary according to the cancer site, disease progression, age and health of the patient. Treatment may include surgery, radiotherapy, chemotherapy and/or hormone therapy. Current therapy regimes typically include a combination of off-patent and patented drugs, a number of which are injectable.

Generic companies currently active in the anti-cancer injectables market include Abraxis Pharmaceutical Products (APP), Baxter Healthcare, Bedford Laboratories, Mayne Pharma, Pharmachemie (Teva), Pliva-Lachema, Sandoz, Sicor (Teva), Spectrum Pharmaceuticals and SuperGen. A number of the older reference drugs are no longer marketed by the originator companies, although generics remain available.

Among the most recently available generics are mitoxantrone, octreotide and carboplatin. Carboplatin became fully open to generic competition in the US in October 2004, since when the FDA has approved 15 ANDAs for eight companies.

Questions, Questions
Which company has the most comprehensive portfolio of FDA approved anti-cancer injectables?
What will the market value of docetaxel (Taxotere - sanofi-aventis) be in 2010?
In which countries does Pliva market its generic version of sanofi-aventis' Eloxatin (oxaliplatin)?
Which companies have received tentative FDA ANDA approval for generic ondansetron injection?

Cardiovascular Disorders
Thrombosis

Venous thrombosis is the third most common cardiovascular disorder in the US, affecting almost two million people each year. Of these, around 60,000 will develop a pulmonary embolism, which will prove fatal in 8-10% of cases.

Venous thrombosis is commonly treated with anticoagulants. Parenteral anticoagulants include heparin, low molecular weight heparins (LMWH) such as bemiparin, dalteparin, enoxaparin, reviparin, and tinzaparin, or synthetic alternatives such as fondaparinux. The most commonly prescribed LMWH in the US and major European markets is sanofi-aventis' Lovenox/Clexane (enoxaparin), with sales of over US$2.8 billion in 2005, of which US$1.6 billion was in the US.

There have already been a number of ANDA applications for generic enoxaparin, including from Amphastar and Teva in 2003, which have been the subject of patent infringement litigation. More recently, Novopharm (Teva) and Momenta Pharmaceuticals have submitted ANDAs for generic enoxaparin.

Between 2000 and 2005, the number of prescriptions dispensed for parenteral anticoagulants in England increased from around 27,600 to 87,600. The majority of these were LMWHs; around 79,900 prescriptions of LMWH were dispensed in England in 2005 at a net ingredient cost (NIC) of around £8.2 million (US$14.9 million). During this period, enoxaparin has taken market share from other LMWHs.

Global sales of enoxaparin in 2005 amounted to EUR 2,143 million (US$2,757 million). Outstanding issues relating to patent protection may mean the entrance of generic enoxaparin in the US is delayed until 2012.

Gastrointestinal

In any year, up to 40% of the adult population in the UK suffer from dysfunction of the upper gastrointestinal tract. Of these, gastro-oesophageal reflux disease (GORD) accounts for 15-20%, gastric and duodenal ulcers account for 15-25% and stomach cancer for 2%. The remainder of causes are classified as non-ulcer dyspepsia. According to the National Institute for Health and Clinical Excellence (NICE), the most clinically and cost effective treatment for severe GORD is offered by proton pump inhibitors (PPIs). In milder cases, NICE guidance states that PPIs remain the most clinically effective treatment, but may not be cost effective.

The world market for PPIs is around US$21 billion, of which the US accounts for around 60%. Branded PPIs currently available in the US and Europe include AstraZeneca's Losec/Prilosec (omeprazole) and Nexium (esomeprazole), TAP Pharmaceuticals' Prevacid (lansoprazole), Wyeth's Protonix (pantoprazole) and Eisai's Pariet/Aciphex (rabeprazole sodium). Of these, esomeprazole, lansoprazole and pantoprazole are available in IV formulations.

Protonix IV (pantoprazole) was the first intravenous PPI to be approved in the US, in October 2001, and could be the first to face generic competition. It is currently the subject of patent litigation. Prevacid IV (lansoprazole) and Nexium IV (esomoprazole) are relatively new to the market. Prevacid IV was approved by the US FDA in May 2004. Nexium IV was approved in Europe in 2004 and in the US in March 2005.

The market for injectable PPIs is relatively small in comparison with oral formulations. Injectable PPIs are used mainly in hospitals for patients who are unable to take oral forms and typically cost 5-6 times as much as the same dosage of the oral form.

Anti-Infectives
Cephalosporins and other anti-infectives

The global anti infectives market is valued at around US$30 billion. The global cephalosporins market is worth around US$9.7 billion annually. While the bulk of the market is oral cephalosporins, around 27% is sterile (injectable) cephalosporins, equivalent to US$2.6 billion.

There are a number of generic injectable cephalosporins already on the market. Between March 2000 and September 2006, the FDA approved 28 ANDAs for generic injectable cephalosporin APIs and formulations: cefotaxime (five), cefazolin (four), cefuroxime (two), ceftriaxone (14) and cefoxitime (three).

The most recent to come off patent in the US was Rocephine (ceftriaxone sodium) in July 2005. Sales of Roche's world leading injectable antibiotic exceeded US$1 billion in 2003 and 2004; faced with generic competition in 2005, sales of the branded product declined US$746 million. Lupin was first to achieve FDA ANDA approval for its generic version of ceftriaxone, followed by Sandoz, Orchid and Baxter. The basic patent for Maxipime (cefepime hydrochloride) will expire in March 2007, although there are two other patents on this drug which run until February 2008. Nonetheless, Orchid has already unveiled plans to launch generic cefepime onto the US market.

In addition to cephalosporins, the report looks at piperacillin sodium, fluconazole, ciprofloxacin and levofloxacin.

Biopharmaceuticals

Biotech drugs account for around 10-15% of the global pharmaceutical market, and the sector is outperforming the market as a whole. The issue of the manufacture, approval and marketing of generic biotechnology drugs, or biosimilar drugs has become a major source of debate within the industry. Most generic manufacturers have an interest in this sector.

In Western markets, the biosimilar sector is a new one and there are severe difficulties for potential manufacturers. An approval path exists in the EU, and has now been used successfully by two companies: Sandoz and BioPartners, both gaining approval for biosimilar human growth hormone. The US offers only very limited prospects for the foreseeable future. The ‘Access to Life-Saving Medicines Act' offers some hope but is sure to provoke a strong reaction from the originator industry, which will disagree with just about every provision. For the time being biosimilars are effectively frozen out of the world's biggest market.

Company Information
Generic substitution by health payers has continued apace and, allied with a generally low commercialisation of new drugs, this has spurred the market to double digit growth.

However, much of that growth has been in mainstream drugs with tablet/capsule administration, and oversupply in some areas has led to low margins for generic companies.

The injectable generic business is bucking this trend. Relatively few companies produce injectables but a favourable cocktail of high prices, good yields and new market opportunities is likely to make the sector more attractive to a wider range of companies.