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Japan greenlights 6 drugs; first-ever nod to programmed cell death protein-1 drug


By Catherine Makino
Contributing Writer

TOKYO – Japan's Ministry of Health, Labor and Welfare (MHLW) approved six new drugs, including one biosimilar, underscoring the country's drive to speed up drug approvals. And, in some instances, the approvals were done faster than in the U.S.

There are two reasons Japan is speeding up its approval process, according to Atsushi Seki, an analyst covering the Japan pharmaceuticals and health care sector at Barclays, a British multinational banking and financial services firm.

The first is that the Japanese regulator, the Pharmaceuticals and Medical Devices Agency, has "increased the number of staff significantly to expedite the review process," Atsuki told Bioworld Today.

The second reason is the introduction of the New Drug Premium in 2010 to reward innovation. The premium kept prices stable without biennial price cuts and made it easier for pharma and biotech companies to accelerate or boost investment in drug development in Japan.

"Patients are now benefiting from these efforts," he said.

The most tangible result of those changes has been faster drug approvals. The MHLW has approved six new drugs just in past few days.

Most notable is Opdivo (nivolumab), which Japan's Ono Pharmacuetical Co. Ltd. developed with U.S. pharma Bristol-Myers Squibb Co. (BMS), to treat unresectable melanoma. Opdivo is now the first approved drug in the world targeting programmed cell death protein-1, or PD-1, according to the company. Ono announced the approval July 7.

Because of the limited number of patients in Japanese clinical trials that were treated with the drug, Ono will have to carry out postmarketing studies to collect more safety and efficacy data. Still, the approval is good news for the company.

"The company will now seek approval for additional indications on ongoing development for other cancers to bring many patients Opdivo as soon as possible," said Gyo Sagara, Ono's president and representative director.

Ono will market the drug in Japan, South Korea and Taiwan, while BMS will keep worldwide marketing rights.

In the U.S., BMS said in April it will pursue a rolling new drug application to complete by the end of this year, though competitor Merck & Co. Inc. already filed with the FDA for approval of its PD-1 inhibitor, MK-3475 (pembrolizumab). (See BioWorld Today, May 7, 2014.)

Beyond Opdivo, Japanese cancer patients also will soon have access to Roche AG's alectinib, approved this week for the treatment of non-small-cell lung cancer (NSCLC) that is anaplastic lymphoma kinase fusion gene-positive (ALK-positive). Chugai Pharmaceutical, which is majority owned by Roche, said it will be available in Japan later this year.

In the U.S., alectinib recently was granted breakthrough therapy designation by the FDA for patients suffering from ALK-positive NSCLC.


Also approved in Japan this week was Daklinza (daclatasvir), the first all-oral, interferon and ribavirin-free hepatitis C treatment in combination with Sunverpra (asunaprevir) from Princeton, N.J.-based BMS. The approval of Daklinza means hepatitis C virus (HCV) patients in Japan that do not respond well to other treatments now have one more option. Older patients or patients with compensated cirrhosis are likely to benefit most, along with patients who are interferon-ineligible or intolerant.

There are about 1.2 million people living with HCV in Japan, of which approximately 70 percent have genotype 1b.

"Japan has a unique hepatitis C patient population, many of whom are older and have been unable to take, or respond to, traditional therapies, so we have a real sense of urgency to treat these patients now," said Kazuaki Chayama, of Hiroshima University. "The approval of the Daklinza [plus] Sunvepra dual regimen offers for the first time a treatment option that addresses many of the unmet needs for our HCV patients."

A giant leap forward for tuberculosis (TB) patients came with the recent approval of Otsuka Pharmaceutical's Deltyba. The first new TB drug approved in Japan in four decades, Deltyba is a nitro-dihydro-imidazooxazole derivative that was also granted conditional approval in the European Union for pulmonary multiple drug-resistant (MDR)-TB.

"The number of tuberculosis patients in Japan has declined year by year; however, with an estimated 20,000 patients, the country still has one of the highest TB rates among highly developed countries," according to Otsuka. "The cure rate for MDR-TB has not improved over the past decade, complicating the elimination of TB in Japan."

The declining efficacy of existing TB drugs has a real impact on health care in the country, extending hospital stays among MDR-TB patients and reducing cure rates.

"Japan marks the first regulatory approval for Deltyba in Asia, paving the way for access in a region of the world with a particularly high burden of the disease," said Patrizia Carlevaro, managing director of Otsuka SA, the public health office of the company's Global TB Programme based in Geneva. "Otsuka has had a TB development program for over 30 years and the ability to now provide access to Deltyba represents a major step forward for the TB community."

Japan is the second location to approve Deltyba, following the European Commission's nod in April. A phase III trial for Deltyba fully enrolled patients last November.

"Because Deltyba is a novel therapy, it will be important that the drug's introduction to market be handled thoughtfully to avoid potential resistance. That is why Otsuka is focusing on rational use, not sales maximization," Carlevaro said.


A fifth drug approved was Canaglu (canagliflozin hydrate), developed by Osaka-based Mitsubishi Tanabe Pharma Corporation and Tokyo-based Daiichi Sankyo Co. Canaglu is an SGLT2 inhibitor used to treat type 2 diabetes mellitus in adults and is the first orally bioavailable sodium glucose co-transporter inhibitor, according to Daiichi Sankyo. Mitsubishi Tanabe Pharma will manufacture and market Canagul the drug and the two companies will co-promote it.

Canaglu is already available in the U.S. under the brand name Invokana, distributed by Johnson & Johnson.

The MHLW also approved a biosimilar to infliximab, developed jointly by Tokyo-based Nippon Kayaku Co. Ltd. and South Korea-based Celltrion Inc. The drug, a biosimilar of Remicade (Johnson & Johnson) is a monoclonal antibody for use in rheumatoid arthritis, inflammatory bowel disease and other autoimmune disorders.