TOKYO – Japan's Taiho Oncology Inc. won U.S. FDA approval for its oral combination anticancer drug TAS-102 (trifluridine hydrochloride) for refractory metastatic colorectal cancer (mCRC), which is marketed in Japan under the brand name Lonsurf.

TAS-102 is used in patients who have not responded to other treatments such as chemotherapy or biological therapy. The approval was based on results from a global randomized, double-blind study with 800 patients that had been previously treated for mCRC.

"We are very excited about the approval because Lonsurf is the first FDA-approved product for the company," Taiho spokeswoman Yukie Shibata told BioWorld Asia. "Our products have been available for years in the Asian and the European markets, but have never been released in the U.S., the biggest pharmaceutical market in the world. Lonsurf is a very important product for Taiho to be a truly global company."

TAS-102 was first approved in Japan in March 2014 based on the results of phase II trials done in Japan. Marketing started in May 2014.

With its first US FDA approval done, Taiho is now looking to bring more new drugs into the global market.

"Lonsurf is currently our only product in the U.S., so for us to expand more into the international market, product life cycle management of Lonsurf such as expanding indications is important," Shibata said. "It is important that additional new oncology products currently on Taiho's pipeline will follow Lonsurf and will be on the international market in the coming years."

To market this new drug, Taiho Oncology Inc., a subsidiary of Taiho Pharmaceutical Co. Ltd., of Tokyo, will go through its commercial organization, which it built in the U.S., including a field sales force to launch the drug.

"We won't disclose the exact numbers of our commercial organization, but a sales unit of less than 100 sales representatives will be enough to cover the U.S.," Shibata said. TAS-102 is manufactured in Princeton, N.J.

Shibata also noted that the Japanese pharmaceutical market is mature and since international pharmaceutical companies have been coming into the Japanese market, it is important for Japanese pharmaceutical companies to go abroad to keep growing.

A STRONG ONCOLOGY BASE

At the same time, "Taiho is already recognized as a leading oncology company," said Kyle Murphy, managing director and founder of KMG Japan. "This approval simply reinforces what industry people already knew."

Colorectal cancer is the second leading cause of cancer-related deaths in the U.S, according to the National Cancer Institute. In Japan it is projected to be the leading cancer in 2015 and the second cause of death with 50,600, according to the Japanese Cancer Information Service.

The rise in colon cancer among younger Japanese has been blamed on lifestyle issues including drinking and unhealthy diets, just as a decline in colon cancer in people older than 50 has been attributed to better screening and regular colonoscopies.

"Japan leads the world in the diagnosis and treatment of CRC. More specifically, as presented at academic conferences and the Japanese Society for Cancer of the Colon and Rectum [JSCCR] and in medical journal articles, Japan ranks highest in the world in terms of the level of diagnosis and treatment provided by institutions specializing in CRC treatment," wrote Kenichi Sugihara, president of the JSCCR.

In phase III trials done in Japan in July 2014, TAS-102 showed statistically significant improvements in overall survival in patients with refractory mCRC that had progressed after using approved standard therapies such as chemotherapy and biological therapy. (See BioWorld Today, July 2, 2014.)

Taiho estimated that there were 136,830 patients diagnosed with cancer of the colon or rectum in 2014 and an estimated 1.1 million people living with the disease in 2012. Among those, 27,400 patients will see their cancer spread to another part of the body.

Shibata said Lonsurf reduced the risk of mortality by 32 percent when compared to placebo.

The median overall survival for patients treated with TAS-102 was 7.1 months (95 percent CI:6-5-7.8) and improvement of 1.8 months over the expected 5.3 months using other therapies. At the same time, there was a statistically signification 52 percent decrease in the risk of the disease progressing. Additionally the disease control rate of patients treated with TAS-102 was 44 percent vs. 16.3 percent for patients treated with placebo.

There were some adverse effects including anemia, neutropenia, leukopenia, diarrhea, nausea and vomiting.