Overview of the Japanese Rapid Introduction Premium as a drug pricing framework to enhance patient access to innovative drugs

Abstract

The pricing of new drugs plays a critical role in patient access by influencing where and when pharmaceutical companies choose to launch their products. The United States (US) operates a predominantly market-based pricing system, in which pharmaceutical companies set and manage drug prices under private health insurance. In contrast, Japan has a government-regulated drug pricing system under its National Health Insurance (NHI). On average, drug prices in the US are 3.2 times higher than those in Japan. The US system facilitates faster patient access to new drugs through rapid market entry, whereas market entry in Japan has often been delayed. To address this issue, the Japanese government introduced the Rapid Introduction Premium in April 2024, aiming to promote earlier launches of new drugs by narrowing the price gap with higher-priced markets such as the US. In this review, we provide an overview of the new drug pricing framework associated with the Rapid Introduction Premium.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13561-025-00705-9.

Background

Drugs have both beneficial and harmful effects on humans; therefore, their quality, effectiveness, and safety must be ensured through a rigorous approval process before a new drug is introduced to the market. This process is coordinated internationally to facilitate the efficient development of new drugs by pharmaceutical manufacturers.

The prescription drug pricing framework plays a crucial role in enabling patient access to pharmaceutical therapies, as price strongly influences a manufacturer’s decision to develop a new drug and conduct clinical trials for its launch in a particular country. However, drug pricing systems differ substantially between countries, leading to significant variations in actual drug prices. For instance, drug prices in the United States (US) are 3.6, 3.2, and 4.1 times higher than those in the United Kingdom, Japan, and Canada (Ontario), respectively [1].

The US is often the first country where drug companies sell the drugs [1]. The US has a relatively free-market pricing system, in which pharmaceutical companies determine and manage drug prices, and private health insurance covers most of the population [2]. In contrast, Japan has a government-controlled pricing system, under which the National Health Insurance (NHI) covers drug costs for all residents. Drug prices in the US are, on average, 3.2 times higher than those in Japan [1]. The US pharmaceutical market—currently the largest in the world—is projected to grow by 2.5% to 5.5% annually between 2023 and 2027. In contrast, the Japanese market is expected to decline by 0.3% annually due to government-driven price reductions aimed at controlling healthcare costs in its progressively aging society [3].

The shrinking Japanese market poses a major challenge for ensuring timely patient access to new drugs from global manufacturers [4]. This reduces incentives for global manufacturers to prioritize Japan in their launch strategies. To address this, the Japanese government has established pricing frameworks to improve access to innovative medicines. One such framework is the Sakigake (meaning “pioneer” in Japanese) Premium, which promotes the early introduction of innovative drugs in Japan by allowing a 10%–20% price increase. However, several stringent criteria must be met: the drug must demonstrate highly significant effectiveness, meet a substantial unmet medical need, and be developed and submitted for approval in Japan before anywhere else in the world [5]. Due to these strict requirements, applications under the Sakigake Premium system have been limited.

To further promote timely access to innovative drugs, the Rapid Introduction Premium framework was introduced in April 2024. As of March 2025, four drugs have been approved in Japan under this framework; two of these have also been launched in the US.

In this review, we introduce the Rapid Introduction Premium pricing framework and examine its potential impact by comparing these two drugs, considering the contrasting pricing environments between the US, which operates under a free-pricing system, and Japan's government-controlled market because the US is the largest market and Japan is the largest pharmaceutical market controlled by the government.

This comparison is important to understand the strengths and the weaknesses of free-priced market and the controlled market, because the US is the representative of free-market and Japan is one of the largest regulated pricing market.

Drug pricing framework in the United States

Internationally, pricing markets can be broadly classified into free-pricing and controlled-pricing systems [2]. The US has a relatively free-pricing market, with drug pricing frameworks comprising both private and public systems.

In the private system, pharmacy benefit managers (PBMs) play a central role in the free-pricing approach, overseeing the financing and distribution of medications for patients (Fig. 1) [6]. PBMs balance the needs of stakeholders—pharmaceutical companies seeking to maximize profits, insurance companies aiming to minimize drug-related expenditures, and patients who wish to access innovative therapies at affordable prices [6]. To manage these competing interests, PBMs often employ a step therapy framework, in which a patient may access an alternative drug only if the initial drug proves ineffective. This prior authorization process discourages physicians from prescribing more expensive drugs without insurer approval, effectively restricting which patients can receive certain therapies. While this approach helps control costs, it can also limit patient access to innovative medicines [6].

Fig. 1.

Flow charts of the negotiation and payment processes in pricing of prescription drugs in Japan and the United States

For privately insured patients, PBMs negotiate rebates with pharmaceutical companies based on a drug’s list price and total sales volume. This rebate-based pricing model incentivizes manufacturers to set high list prices, contributing to elevated drug prices in the US [6].

In the public system, the Veterans Administration (VA) healthcare program negotiates prices directly with manufacturers as part of its comprehensive drug formulary, resulting in lower prices compared with those of Medicare [2]. Historically, both Medicare and Medicaid were prohibited from direct price negotiations with pharmaceutical companies. However, the Inflation Reduction Act (IRA), signed in August 2022, authorizes the US Secretary of Health and Human Services to negotiate prices for certain drugs covered under Medicare [2]. If effectively implemented, this could bring Medicare drug prices closer to those of the VA [2].

The US is often the first country to introduce a new drug, meaning there are no international price benchmarks available at launch [1]. While high drug prices remain a domestic concern, some experts suggest that although reference pricing may be impractical for new drugs at launch, it could be applied to established drugs—such as those on the market for more than three years—by referencing prices in other countries [1].

The VA’s lower drug prices come at the cost of a more limited formulary [7]. Furthermore, it is widely argued that lower prices could hinder pharmaceutical innovation. Under the IRA, the number of drugs subject to negotiation is expected to increase annually [2].

Drug pricing framework in Japan

In both Japan and the US, drugs are sold by pharmaceutical companies to wholesalers, who then sell them to pharmacies for dispensing based on prescriptions (Fig. 1). In Japan, the price at which a pharmaceutical company sells to a wholesaler is negotiated between the two parties and may include rebates and allowances [8]. Similarly, wholesalers negotiate sale prices with pharmacies (the wholesale price). Despite these negotiated prices, the final price charged to patients is set by the government.

Japan operates a universal health insurance system, with a fixed patient co-payment ratio. The National Health Insurance (NHI) drug price, minus the patient’s co-payment, is reimbursed to the pharmacy by the insurer via a payment fund [9].

When a new prescription drug is approved, the initial NHI price is determined using either the cost calculation method or the comparative method (Supplementary Information 1, Fig. 2). The choice depends on the approval status of similar drugs—defined as listed drugs with comparable indications, pharmacological action, composition and structure, administration route, dosage form, and dosing regimen. If the drug demonstrates superior usefulness compared with a similar drug, a correction premium may be added to its NHI price. Currently, seven types of premiums are available (Supplementary Table 1, Supplementary Information 2).

Fig. 2.

Methods used by the drug pricing organization of the central social insurance medical council for setting the initial NHI drug price for a new drug

The NHI price is reviewed every two years, and in principle, the price is lowered during revisions. The government conducts surveys of actual wholesale prices from wholesalers, selected pharmacies, and medical institutions. The new price is then set based on the weighted average of surveyed wholesale prices, plus an additional 2% of the pre-revision NHI price. The selection of drugs eligible for price revision is based on both the overall average deviation rate and the deviation rate for individual drugs.

Beyond routine biennial revisions, the government may add innovation premiums, recalculate prices to maintain the sustainability of universal healthcare, and make adjustments in response to market or policy changes. Price revisions can also be implemented between regular review periods if deemed necessary [10].

Under the NHI scheme, drug prices are uniformly set by the government. This centralized pricing system ensures equitable access to all approved medications, minimizing financial burdens on patients. However, while this model effectively maintains affordability, its rigid cost-control mechanisms may reduce incentives for pharmaceutical innovation. As a consequence, the Japanese market is sometimes considered less favorable for launching high-cost, cutting-edge drugs, particularly when compared to more flexible pricing systems abroad.

Introduction of the Rapid Introduction Premium in Japan

In Japan, two major issues affect access to new drugs: drug lag—the delay between a drug’s approval in the US and its approval in Japan—and drug loss, in which drugs approved in the US never become available in Japan [4]. Drug lag can be further divided into development lag, the gap between a company’s application for approval in the US and in Japan, and review lag, the difference in review durations between the US Food and Drug Administration and Japan’s Pharmaceuticals and Medical Devices Agency. In recent years, Japan has strengthened its review system by increasing the number of reviewers, effectively eliminating review lag [11, 12]. Nevertheless, data show that overall drug lag in Japan still averaged 14 months over the past three years [3].

Addressing both drug lag and drug loss requires measures targeting development lag—specifically, policies that encourage pharmaceutical companies to submit approval applications in Japan and the US simultaneously. In April 2014, the Japanese government introduced the initial version of Sakigake Premium, which offered a 10% price premium to promote the early development of groundbreaking new drugs in Japan. Eligibility was restricted to drugs approved in Japan before any other country and to those qualifying for either the Innovation Premium or Usefulness Premium I [13]. However, these criteria proved too strict: no drug qualified for the Sakigake Premium during its first two years. Moreover, because Innovation or Usefulness Premium I eligibility could only be confirmed post-approval, companies could not predict during development whether they would qualify [14].

In 2016, the revised version of Sakigake Premium changed the eligibility requirements to include only drugs designated as Sakigake Designated Drugs—a regulatory framework supporting early approval from the development stage for qualifying products [15]. This improved predictability for pharmaceutical companies. While the base premium rate remained at 10%, it could rise to 20% for drugs supported by substantial clinical trial results conducted in Japan.

Despite these revisions, at the 2023 Central Social Insurance Medical Council meeting, pharmaceutical industry representatives argued that Japan’s relatively low drug prices still discouraged early launches and that the Sakigake Premium requirements remained too stringent to provide sufficient incentives. The Council concluded that a new premium—featuring less restrictive criteria and stronger incentives—was needed [16, 17]. In response, the Rapid Introduction Premium was introduced in April 2024.

As of March 2025, four drugs had been newly listed on Japan’s NHI drug price list under this framework. Two received a 10% premium and two received a 5% premium. All four met the eligibility criteria; however, those awarded a 10% premium had a higher proportion of Japanese participants in their respective international clinical trials, which likely influenced the premium rate [18–20]. Specifically, the proportion of Japanese participants was 12/86 (14%) and 28/63 (44%) for the two drugs with a 10% premium. One drug with a 5% premium had only 10/89 Japanese participants (11%); however, sixteen patients from the international Phase I trial were excluded from this calculation because their nationalities were not reported [21–24]. Another drug, despite having a relatively high proportion of Japanese participants (65/162, 40%), received only a 5% premium, likely because its primary endpoint was not demonstrated to be superior to placebo in overseas trials [23].

Of the four drugs approved in Japan with the Rapid Introduction Premium, only two were also approved in the US: VOYDEYA tablets 50 mg (danicopan) and ADZYNMA Intravenous 1500 (ADAMTS13, recombinant-krhn) [25, 26]. According to the latest Ministry of Health, Labour and Welfare notifications, the Japanese NHI prices for these drugs were $15.08 per tablet and $8,090.96 per vial, respectively (exchange rate as of April 1, 2025: 149.80 JPY/USD) [27, 28]. The premium rates were 10% for VOYDEYA and 5% for ADZYNMA. Without the premiums, their prices would have been $13.71 per tablet and $7,705.68 per vial.

By comparison, US prices—based on the lowest listed values on Drugs.com—were $24.01 per tablet for VOYDEYA and $19,170.00 per vial for ADZYNMA [29, 30]. Using Japanese prices as the reference point, US prices were $8.93 (59.2%) higher for VOYDEYA and $11,079.04 (137.0%) higher for ADZYNMA. Without the Rapid Introduction Premium, the differences would have been $10.30 (75.2%) and $11,464.32 (148.8%), respectively. We selected Japanese prices as the baseline because our primary objective is to evaluate the impact of the Rapid Introduction Premium on domestic drug pricing and its effectiveness in reducing the price gap with the US market. These figures indicates that the premium narrowed the Japan–US price gap by 16.0 percentage points for VOYDEYA and 11.8 percentage points for ADZYNMA (Table 1).

Table 1.

US-Japan price comparison for drugs with Rapid Introduction Premium

Drug	Application/approval timing		US Price (USD) (a)	JP Price (USD) (with premium (b)/without premium (c))	Absolute Reduction in Gap (pp)	US/JP (%) (with premium (a/b)/without premium (a/c))
	US	Japan
VOYDEYA	Mar 30, 2023/Mar 29, 2024	May 19, 2023/Jan 18, 2024	$24.01	$15.08/$13.71	16,0	159%/175%
ADZYNMA	May 17, 2023/Nov 9, 2023	Aug 16, 2023/Mar 26, 2024	$19,170.00	$8,090.96/$7,705.68	11.8	237%/249%

The United States (US) prices are based on the lowest listed prices from Drugs.com as of April 15, 2025. Japanese National Health Insurance (NHI) prices are from Japan’s Ministry of Health, Labour and Welfare notifications as of April 2025, converted using an exchange rate of 149.80 JPY/USD. ‘Absolute Reduction in Gap (pp)’ reflects the decrease in the price gap in percentage points. ‘US/JP (%)’ indicates the ratio of US price to Japanese price with and without the premium

Comparison of drug pricing systems between the US and Japan

The US has historically avoided reference pricing, particularly in the private insurance sector. Instead, prices have been shaped by rebate-driven negotiations, which have often resulted in disproportionately high list prices. These elevated prices raise concerns about affordability and equitable access. Consequently, adoption of reference pricing has been increasingly discussed as a policy tool to enhance transparency and contain costs [2].

In contrast, the VA employs a fully government-regulated pricing system, achieving significantly lower drug costs but at the expense of a narrower formulary. Approximately 40% of VA beneficiaries rely on Medicare Part D to obtain certain medications, highlighting this limitation [7].

With the enactment of the IRA, the US government began direct price negotiations for a limited number of drugs covered under Medicare. While initially narrow in scope, these negotiations are expected to expand, potentially increasing financial pressure on manufacturers and raising concerns that incentives for pharmaceutical innovation could diminish. Historically, companies have accepted stringent price controls in other countries because higher US prices offset these constraints [1]. If US prices fall substantially, manufacturers may seek greater revenues from other markets. In this context, earlier regulatory submission in Japan—and use of incentives like the Rapid Introduction Premium—could become a strategic means to secure earlier launches with higher reimbursement values.

Japan, by contrast, operates a government-regulated pricing system designed to balance the evaluation of innovative drugs with the sustainability of universal health coverage. This ensures equitable access, with all citizens receiving the same standard of care. However, low drug prices have delayed submissions of new drug applications. The Rapid Introduction Premium was created to reduce this risk by encouraging earlier launches of drugs that might not qualify for the Sakigake Premium. Its introduction has reduced the Japan–US price gap by 11.8–16.0 percentage points (Table 1).

The Central Social Insurance Medical Council is monitoring the policy’s impact on reducing drug lag and drug loss through ongoing evaluations [31]. In its first year, the premium was applied to four drugs. Of these, two were also approved in the US, and in both cases the premium contributed to narrowing the Japan–US price gap. While this policy may help improve patient access, higher reimbursement prices could also increase the financial burden on Japan’s healthcare system. However, because NHI drug prices are subject to biennial downward revision [10], the long-term affordability risk is expected to be partially mitigated.

For manufacturers, the Rapid Introduction Premium provides an opportunity to obtain earlier approval and launch drugs at premium-adjusted prices in Japan. Nevertheless, future evaluations should assess whether the policy has genuinely improved patient access and how it has influenced companies’ development and regulatory strategies, using both quantitative and qualitative approaches.

Perspective

For Japanese policymakers, the central challenge lies in balancing the objective of accelerating drug availability with the need to safeguard the sustainability of the NHI system. Wider adoption of the Rapid Introduction Premium could provide patients with earlier access to innovative therapies; however, it also necessitates careful monitoring of the associated financial and systemic impact.

Beyond Japan, the experience with the Rapid Introduction Premium may offer useful insights for other Asian countries with regulated pharmaceutical pricing systems and aging populations, whether they are considering similar mechanisms or have already implemented them. While the premium provides a framework to reward timely drug launches, its broader application would require careful calibration. In particular, concerns around affordability, patient cost burden, and health system sustainability must be explicitly addressed. Engaging diverse stakeholders—including healthcare professionals, payers, patients, and manufacturers—in the design and regular reassessment of such policies is essential to ensure they support equitable access while maintaining financial balance. Adaptation to each country’s regulatory, economic, and social context will be critical to achieving meaningful and sustainable impact.

Ultimately, achieving a balance among access, innovation, and affordability will require adaptive governance, transparent communication, and a sustained commitment to inclusive, participatory decision-making.

This review has several limitations. As of March 2025, only four drugs had been launched under the Rapid Introduction Premium, and only two of these were approved in both the US and Japan. Cross-country price comparisons are further complicated by variability in US pricing data, which can be influenced by payer type, distribution channels, and market timing. Moreover, the causal relationship between the premium and companies’ launch behavior remains speculative.

To establish a stronger evidence base, future studies should employ both quantitative and qualitative methods. Quantitative approaches such as propensity score matching or difference-in-differences analyses could help isolate the effect of the Rapid Introduction Premium relative to comparable drugs. Interrupted time series designs could capture broader shifts in launch timing or access metrics. Qualitative research, including stakeholder interviews with regulators, manufacturers, and patient groups, will be essential for assessing real-world perceptions, facilitators, and barriers to implementation.

Conclusions

Despite having fundamentally different systems, both the US and Japan are pursuing drug pricing reforms to improve access to innovation. Japan’s Rapid Introduction Premium may help reduce drug lag by narrowing the price gap with the US, providing incentives for earlier launches, and promoting patient access to new drugs within the framework of controlled pricing and the NHI system. Future evaluations should examine not only the financial sustainability of the policy but also its broader impacts on patient outcomes, pharmaceutical development strategies, and systemic efficiency. Insights from Japan’s experience may inform policy development in other countries facing similar access and affordability challenges.

Abbreviations

NIH

National health insurance

PBM

Pharmacy benefit manager

US

United States

VA

Veterans administration

IRA

Inflation reduction act

Authors’ contributions

**Kento Takamura:** Conception, Analysis, Writing-original draft. **Gai Jinnai:** Analysis, Writing-review and editing. **Yuki Niwa:** Writing-review and editing. **Masuo Kondoh:** Conception, Writing-review and editing.

Funding

This study received no financial support from any source.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Competing interests

The authors declare no competing interests.