The bitterest pill for hepatitis C patients

The current standard treatment is unsuitable for about 50 percent of people diagnosed with the virus, but China's lengthy drug approval system means many look overseas for medication, as Shan Juan reports.

At least one in 10 of the global population with hepatitis C lives in China. However, despite being available in most parts of the world, drugs known as "direct-acting antivirals", or DAAs, which can cure at least 95 percent of cases, are not available in the Chinese mainland.

Hepatitis C affects the liver, and 80 percent of patients develop a chronic infection, according to medical experts.

Initially, many patients display minimal or even zero symptoms, but chronic infection can lead to cirrhosis or scarring of the liver, which can develop into liver failure or cancer over the course of 20 to 30 years.

In China, the current standard treatment for Hepatitis C is a combination of Ribavirin and Interferon, antiretroviral drugs that keep the level of infection low. However, only about 50 percent of patients can endure the severe side effects the drugs provoke.

A recent survey conducted by 28 Chinese hospitals concluded that Interferon is unsuitable for about 50 percent of patients, mainly because of serious adverse reactions, according to Wei Lai, a senior hepatitis specialist and vice-president of Peking University People's Hospital in Beijing.

"All stakeholders including the drug authorities, patient organizations and pharmaceutical companies should work together to bring the new drugs to Chinese patients. It's a race against death," he said.

Currently, several types of DAAs are undergoing the mandatory clinical trials required to obtain approval from the China Food and Drug Administration, a process that usually takes more than five years.

'Fake, illegal drugs'

Some patients, such as Bai Fengshan (not his real name) can't wait that long. Bai decided to look overseas to purchase DAAs, which he said are regarded as "fake, illegal drugs," by the CFDA. Illegal or not, the decision saved his life.

With the help of an online agency, Bai bought the DAAs in December last year, and finished the course of treatment in May.

Thanks to the treatment, Bai has now been clear of hepatitis C for more than 30 weeks, and has been declared cured by medical experts. Survival didn't come easy or cheap, though.

The 50-something Beijing resident was infected during a blood transfusion administered during cardiac surgery in 1989. Chinese blood centers didn't begin routine screenings for hepatitis C until the early 1990s.

When he was diagnosed with the virus in 2003, Bai was put on a combination of Ribavirin and Interferon, which caused serious side effects, such as high temperatures, fatigue, loss of weight and skin rashes.

"I had rashes all over my body, except for my face and hands. I couldn't wear shorts in summer or stay at a hotel. Flakes of dead skin and fluid from the rashes always stained the bed linen," he said. In addition, the medication made Bai so weak that he couldn't perform commonplace tasks, such as driving or bending over to tie his shoelaces.

The "unbearable" adverse reactions resulted in Bai only taking the medication intermittently. "I felt desperate when I injected myself with Interferon near my navel," he recalled.

As the head of an online information support community of more than 2,000 patients, Bai has met many people in the same plight. "Many were struggling with side effects from the drugs that were far more serious than mine. It's a desperate dilemma whether to stick with the medication or not," he said.

The "hope of life" finally came in late 2013, when Sofobuvir, the first major DAA, was approved by the US Food and Drug Administration.

Sofobuvir, manufactured by the US pharmaceutical company Gilead Sciences, can cure 95 percent of patients, compared with the 70 percent rate for current medications, and has fewer side effects. In addition, the drug is administered orally, a far easier method than the injections required with current treatments.

However, a typical 12-week course of Sofobuvir, which has been dubbed a "game changer", costs $84,000, or $1,000 for each pill.

A question of choice

"For many people, life is more precious than money, and patients in China should at least be offered the choice," Bai said, adding that many national governments quickly introduced the drug following its approval by the FDA.

For example, patients who had been infected via contaminated medical procedures in Brazil, Egypt and the United Kingdom were provided with the treatment either without charge or at highly subsidized rates.

"We don't expect that much. We just want the government to allow these drugs into the country faster because patients, particularly those who cannot tolerate Interferon, are suffering and dying," Bai said.

Last year, he wrote to the CFDA, China's top drug authority, calling for an accelerated approval process. The letter was co-signed by more than 100 of his patient peers.

Two months later, he received a response from the administration: "We are highly concerned about the issue, but the procedures for drug approval have to be foll-owed."

Under the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, launched by the US and European Union in 1990, new drugs that have been approved by one member country can be made available in the others with minimal retesting.

It took just three months for Sofobuvir and other DAAs to enter the markets of ICH member countries and regions in Asia, such as Pakistan, Mongolia and Macao.

However, China has yet to join the ICH, and in desperation, many wealthier patients have turned to online agencies and paid for the drugs out of their own pockets.

Treatment costs falling

Initially, the treatment didn't come cheap; a 12-week course of Sofobuvir cost hundreds of thousands of yuan, but the price fell after Gilead Sciences signed a voluntary licensing agreement with seven Indian drug manufacturers in September last year.

Under the agreement, the Indian companies were allowed to produce and sell generic versions of the drug in 91 countries. However, countries with high rates of hepatitis C, such as China, Brazil, Thailand and Mexico, are excluded.

The agreement resulted in the cost of the treatment in India falling to $900, and made the country a hot destination for Chinese patients seeking affordable treatment.

Internationally, many pharmaceutical companies employ a tiered pricing structure, mainly based on income levels standardized by the World Bank. China and several other countries with high rates of hepatitis C are classified as "middle income", meaning that patients are unable to buy drugs at lower prices.

The ruling resulted in some countries resorting to compulsory licensing, making cheaper copies of drugs to ensure treatment for domestic patients.

Zheng Hong, head of pharmaceutical affairs at the National Health and Family Planning Commission, said China has never issued compulsory licensing for any drug. "China lacks related policies, but the patent authorities have been researching the issue," he said.

At present, 16 government agencies - including the National Health and Family Planning Commission, the China Food and Drug Administration, the National Development and Reform Commission and the State Intellectual Property Office - are trialing a centralized drug-purchasing mechanism.

"We've initiated price negotiations with manufacturers of patented drugs in a bid to lower the cost for patients in China," Zheng said.

The negotiations are centered on a treatment for hepatitis B called TDF, which is also manufactured by Gilead Sciences.

Patients excluded from China's health insurance system have to pay 17,000 yuan ($2,630) every year for the drug, which requires long term use.

However, under the country's independent HIV/AIDS centralized drug-purchasing system, a 12-month course of the same drug, which is also used as a treatment for AIDS, costs 1,450 yuan per patient. The Chinese government has provided free treatment for people with HIV/AIDS since 2003.

Wei, of Peking University People's Hospital, urged the government to trial a centralized purchasing system for hepatitis C drugs to lower the price.

There is no vaccine for hepatitis C, so curing patients helps to curb the spread of the virus, which has similar transmission routes to HIV, according to Wei. "It benefits the patients, and has great public health significance," he said.

Most hepatitis C patients in China were infected in the late 80s or early 90s, prior to routine screening at blood centers, and so "the treatment is urgently needed to prevent more cases and save lives", Wei said. Given that cirrhosis medication costs 40,000 yuan a year and treatment for liver cancer is even more expensive, the introduction of TDF "would help reduce the country's medical bills", he added.

Last year, about 350,000 people were diagnosed with liver cancer in China, according to country's official cancer registry. More than 80 percent of cases were caused by chronic hepatitis of various types, and they result in more than 380,000 cancer-related deaths in China every year.

Rising rate of infection

According to Lei Zhenglong, deputy head of disease prevention and control at the National Health and Family Planning Commission, the rates for hepatitis A and B are falling, but the incidence of hepatitis C is rising steadily.

Most cases of hepatitis C in China are the result of exposure to infected blood in situations such as transfusions, dental services and surgeries, and many patients were infected at registered medical facilities, he said.

According to Wei, experts estimate that fewer than 10 percent of hepatitis C cases in China have been detected, and less than 50 percent of those diagnosed with the virus have sought treatment.

The susceptible population includes people who had blood transfusions or organ transplants before 1992, plus individuals whose mother tested positive for the virus, he said, citing the official standards for screening and management set by the National Health and Family Planning Commission.

According to Bai from Beijing, patients in Shanghai who were infected via blood transfusions are now given one-time compensation of 60,000 yuan.

"The issue of saving lives is more urgent now because of a rise in the number of patients who lack the financial resources to buy drugs from overseas," he said.

Wei echoed that view: "The nation's hepatitis C patients cannot be reliant on drug-purchasing agencies."

The practice of purchasing drugs overseas is not a universal panacea, though, and has resulted in a number of problems. For example, patients buy drugs from a variety of outlets overseas, which makes it difficult for physicians to correctly gauge the effectiveness of their treatment and adjust their medication accordingly. Sometimes, patients even bought wrong medication, and overseas purchases also make it difficult to track the development of the disease, according to Wei.

"There is also an international dimension. The need to buy drugs from overseas tarnishes China's international image as an economic power if the basic medical needs of its citizens remain unmet," he said.

However, the authorities are working to make new treatments available, and Wei and his team are building an online hepatitis C virtual community to improve levels of care and facilitate accurate tracking of each patient's medication.

Furthermore, when patients key in their medical information in Chinese, the system will automatically produce an English-language version of their medical records and ailments.

"That would be helpful if our patients want to seek treatment and drugs overseas," Wei said. "What else is a good hepatitis C doctor to do?"

Contact the writer at shanjuan@chinadaily.com.cn