There are five pathways for expedited approval of novel drugs in Japan, but advanced planning is essential, according to Mark Lane, PhD, of PharmaLex.
“You really have to plan your entry into Japan early. If you wait until you’re in Phase 2 to start thinking about what you’re going to do in Japan, the chances that you’ll be able to join in your global program get less and less,” said Lane, vice president of development and scientific affairs at PharmaLex, at RAPS Convergence 2022.
In Japan, as in other countries that offer priority review, the requirement for this pathway is that there is either no standard therapy for the condition or the investigational drug has demonstrated superior clinical utility compared with approved products. The main benefit of priority review, Lane explained, is that the review time is shortened to nine months, from the standard 12 months.
Orphan drug designation
Orphan drug designation is available for treatments with a target population of less 50,000 people. The population target can increase to less than 180,000 people for a designated intractable disease for which the etiology is not well understood, and which may require long-term treatment. The candidate drug must address a serious unmet medical need and lack alternative treatments. Additionally, there must be a “high probability of development success,” Lane said.
There are several benefits in Japan for orphan drug status, including premium pricing, less stringent pricing review requirements, lower user fees, a tax credit, and the potential for subsides for the development program. The review period also is shortened from 12 to nine months.
Additionally, the orphan drug designation has an extended “re-examination period” of 10 years, versus the standard eight years.
“The primary purpose of the re-examination period in Japan is to secure and ensure the safety and efficacy of newly approved drugs,” Lane said. “But in practice, this re-examination period essentially extends data and marketing exclusivity to the originator because another company cannot enter without generating at least the same or more data. And it also requires additional safety and efficacy studies be completed during that review period and then it gets re-examined at the end of the review.”
To qualify for breakthrough designation, or Sakigake, the candidate drug must have a new or different mechanism of action from already approved drugs. Much like in the other accelerated categories, the drug has to treat serious or life-threatening diseases and demonstrate greater efficacy over existing treatments is expected.
To qualify for this category, the drug must either be first registered in Japan, or the marketing authorization application must be made within 30 days of having submitted the application elsewhere. The point of this requirement is to bring products first to Japan, Lane said, “ahead of, or closely simultaneous with, everywhere else and not two, three, four years later.”
The benefits include that the review period is shortened to six months, there is a rolling review of the application, and there is a “concierge” review. The concierge review means that there is a manager from the Pharmaceuticals and Medical Devices Agency (PMDA) assigned to shepherd the application through marketing authorization. Additionally, the re-examination period can be extended out to 10 years and there is a premium pricing benefit.
Conditional early approval
There are a lot of similarities between conditional early approval in Japan and in other countries, Lane said. The pathway offers limited-term marketing authorization of up to seven years for a novel drug that treats a serious disease. Additionally, there must be known challenges for conducting the Phase 3 or confirmatory studies, such as a disease with a limited number of patients or a study that would be challenging to enroll. The early clinical trials must have demonstrated a significant degree of efficacy and safety and post marketing studies are likely to be required, Lane said.
Conditional early approval allows for a shortened review period of nine months. Additionally, drugs that go through this pathway are eligible for reimbursement and can be sold with limited clinical trial data while being developed in other countries. “There’s some real benefits for moving these types of products into Japan as well,” Lane said.
Specific usage drugs
The pathway for specific usage drugs is mainly for pediatric drugs and for drugs to treat diseases caused by drug-resistant pathogens. The drug must be established already as a standard therapy in adults or supported by a high level of evidence before moving into the pediatric population. The benefits of this pathway include shortened review periods and prioritized consultation.
Lane noted that while these pathways offer the ability to get onto the market faster, they also offer additional consultation opportunities, which can result in a better product making into onto the market.
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