As the levo isomer of ofloxacin, levofloxacin belongs to the third-generation quinolone antibacterial agent; its antibacterial spectrum is same as ofloxacin, but its antibacterial action is 1 time stronger, and its toxicity is lower; it is clinically indicated for dozens of infectious diseases. The market performance of levofloxacin was eye-catching after marketing owing to its strong antibacterial action, good efficacy, and small side effects, etc., with the sales continuing to grow and the product rapidly becoming a star product on Chinese and foreign markets.

However, levofloxacin has shown weak growth and flat tendency on the Chinese pharmaceutical market in recent years. How its future performance will be is worth noting.

Glorious history

First developed and marketed in Japan by Daiichi Pharmaceutical in 1994, Levofloxacin was approved to be marketed in the U.S. in 1995. Levofloxacin enjoyed hot sales on the market with sales constantly rising after marketing owing to its strong antibacterial action and small adverse reactions, etc.: its global sales reached USD 550 million in 1998, USD 700 million in 1999, and USD 1.09 billion in 2000 ranking 37^th on the list of global top 200 best-selling drugs. Also in 2000, levofloxacin surpassed ciprofloxacin for the first time, to top the global sales of quinolones; in 2010, it achieved the outstanding global sales of over USD 2 billion.

Topping the rankings for years

The levofloxacin API and tablet of Daiichi Pharmaceutical were approved to enter the Chinese market in 1995. The company later established a joint venture in Beijing, and had Daiichi Pharmaceutical Co., Ltd. provide API, and the joint venture Youerte Pharmaceutical Company sub-package and produce tablets, and sell the tablets on the Chinese market with trade name of Cravit in 1996. In 1998, levofloxacin entered the top 100 pharmaceutical products by sales in sample hospitals of major Chinese cities only after more than 1 year of marketing, ranking 98^th; it quickly ascended to the 21^st in 1999, 5^th in 2000, and 3^rd in 2001 ranking 1^st among anti-infective drugs, and its sales in sample hospitals of major Chinese cities reached RMB 600 million in 2005. For over a decade thereafter, levofloxacin had been the leader of quinolone market in China. Many Chinese pharmaceutical enterprises joined levofloxacin production because of the optimism about the huge market space thereof. According to statistics, there are over 800 production approval numbers and over 300 manufacturers of levofloxacin in China.

Market stagflation in recent years

With the heavy use of levofloxacin in recent years, the resistance of bacteria has been growing, and the adverse reactions have increasingly showed. Some time ago the market of levofloxacin showed stagflation due to the strictest restriction order of antibiotics usage in the history of China plus the strong market competition of new antibacterial agents. Its market sales remained stable in 2014-2016, with size all reaching above RMB 800 million, however, it started to show negative growth. Levofloxacin had been the number one on the quinolone market in China over a decade, however, it was surpassed by moxifloxacin in 2016, to ranked second.

Analysis of future prospects

According to analysis, there are favorable and unfavorable factors for the future market development of levofloxacin in China, which will enter the momentum of steady growth.

Unfavorable factors mainly include: firstly, the restriction order of antibiotics usage will have long-term impacts. China now divides antibacterial drugs into restricted use level, unrestricted use level, and special use level, similar to the new standard of the World Health Organization, and there is a strict restriction on doctors’ right to prescribe those 3 levels of antibacterial drugs. The proportion of purchase quantity of antibacterial drugs in total purchase quantity of pharmaceutical products has been declining year by year in big and medium hospitals of major Chinese cities after years of strict restriction on antibiotics usage, already from the previous 35%-40% to 15%-20%, and will gradually decline in the future. According to the drug use data of sample hospitals of major Chinese cities, the compound annual growth rate (CAGR) of purchase amount of quinolones in recent decade was only 3.3%, far lower than the average of the pharmaceutical product industry.

Secondly, after years of application, resistance of bacteria to levofloxacin continues to grow, levofloxacin’s application effects are wearing off, and new quinolones such as moxifloxacin are more favored clinically. In addition, the side effects of levofloxacin, especially the injections, have gradually showed after heavy use, which impacts its further market expansion.

Thirdly, new quinolones such as moxifloxacin have rapidly risen in recent years, to seize the market shares of levofloxacin. Marketed in 1999 as the fourth-generation extended-spectrum quinolone antibacterial agent, moxifloxacin entered the Chinese market in 2002. According to drug use data of sample hospitals of major Chinese cities, the sales of moxifloxacin reached RMB 58 million in 2005, and up to RMB 910 million in 2016, with CAGR up to 28.5%, far exceeding the average 3.3% of quinolone antibacterial agents, while the market growth of levofloxacin has been weak in recent years, with the growth turning from positive to negative. More importantly, moxifloxacin topped the sales of quinolones for the first time in 2016, and put levofloxacin that was in that position for a dozen years behind. Moxifloxacin is expected to continue to nibble the market of levofloxacin in the future.

After talking about the unfavorable factors, next let’s talk about the favorable factors for the future market development of levofloxacin, mainly including: firstly, the pharmaceutical market of China has been developing at top speed since the reform and opening up, with the total market continuing to grow. According to data, the CAGR of China’s pharmaceutical product consumption in 2002-2013 reached nearly 20%, showing good growth. The total size of the entire pharmaceutical product consumption market of China was RMB 208 billion in 2002, it exceeded RMB 1 trillion in 2013, and reached RMB 1.5 trillion in 2015, with the growth generally remaining at about 16% in recent years. The overall size of the Chinese pharmaceutical market will continue to grow, and the demands for various drugs will not reduce.

Secondly, China has a very huge population of 1.4 billion. In recent years, China has been further promoting the social security system reform and accelerating universal social security coverage plan, and governments at all levels have also been increasing the investment in medical insurance. Currently, there have been more than 1.3 billion people participating in various medical insurances in China, with the security level rising year by year with the economic development. Such a huge market will facilitate the antibacterial drug market to keep steady growth for some time to come. There will still be some room for the market development of levofloxacin that is a major antibacterial product on the Chinese pharmaceutical market.

Thirdly, levofloxacin has become a star antibacterial drug on the Chinese pharmaceutical market since the beginning of the 21^st century, with sales having been ranking high among antibacterial agents, with high awareness among hospitals, doctors, and the people, thus has initiative on the market. The sales of levofloxacin in sample hospitals of major Chinese cities reached RMB 880 million in 2016, showing quite a huge scale. In 2016, it was surpassed by moxifloxacin and ranked second among quinolones, second to the RMB 910 million of moxifloxacin, however, it far exceeded the RMB 28.87 million of ofloxacin that ranked third, and was at the forefront together with moxifloxacin.

Fourthly, the selling price of levofloxacin is much low: the levofloxacin injection is about RMB 30/piece (100ml/200mg) on the Chinese market, and the Chinese-produced tablets are about RMB 1/tablet (100mg), and the imported tablets are about RMB 4/tablet (100mg). The price of moxifloxacin is much higher: the moxifloxacin injection is about RMB 330/piece (250ml/400mg), and the tablets are about RMB 30/tablet (400mg), both several times higher than levofloxacin. Levofloxacin was surpassed by moxifloxacin in sales of sample hospitals of major Chinese cities in 2016, with the sales about RMB 30 million less than those of moxifloxacin, however, the sales volume of levofloxacin was far more than that of moxifloxacin. In addition, the sales volume of levofloxacin in medium and small grass-roots hospitals and broad pharmacies in China far exceeded that of moxifloxacin. The cheap levofloxacin more accords with the realities of "low level, wide coverage" of the medical insurance in China, and levofloxacin’s market sales are expected to experience stable development in the future.

Zhang Lun of Nanjing