Thank you very much for taking time out of your busy schedule to join us today for Takeda's financial results webinar for the second quarter of fiscal year 2022. My name is Ayako Iwamuro. I am in charge of IR. I will be your moderator today. Very nice to meet you. First, let me explain the language settings. At the bottom of the Zoom window, there is a language button. If you prefer to listen in Japanese, please select Japanese. If you prefer to listen in English, please select English. Or if you prefer to listen to the live audio, please select off. For those of you who wish to listen to this call in English, please click the language select button at the bottom of your window, Zoom window, and then select English.
Before starting, I'd like to remind everyone that we will be discussing forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those discussed today. The factors that could cause actual results to differ materially are discussed in our most recent Form 20-F and in our other SEC filings. Please also refer to the important notice on page two of the presentation material. I would now like to turn to today's presentation. Let me introduce to you today's presenters. First, Christophe Weber, President and CEO. Andy Plump, President, R&D. Costa Saroukos, Chief Financial Officer. They will be giving the presentation. The presentation will be followed by a Q&A session. I'd now like to begin. Christophe, over to you.
Thank you. Thank you very much, Ayako, and thank you everyone for joining us today. It's a really great pleasure to be with you. On the first slide, I would just summarize that at Takeda, our vision is to discover and deliver a life-transforming treatment guided by our commitment to patient, our people on the planet. This is a purpose-led approach, which is at the core of our strategy for global growth and long-term value creation for our stakeholders. Our performance in the first half of the fiscal year further demonstrate our progress in executing on that strategy as we look to accelerate growth, advance our pipeline, and deliver on our commitment. I will move to slide five, if someone can move the slide. Yes. Thank you. On slide five, I would like to take you through some of the recent highlight.
In the first six months, our core revenue was JPY 1,974.8 billion, which represent a 5.5% growth at a constant exchange rate. Core profit for the period was JPY 625.2 billion, growing at an impressive 14.5%, also on a constant exchange rate basis. This enable us to deliver a strong core profit margin of 31.7%, an improvement of 2.4 percentage point versus prior year. Core earning per share was JPY 288, with growth of 15.8% at, again, constant exchange rate. Based on these strong results, we are reconfirming the full year management guidance for low single digit core revenue growth and high single digit core profit and core EPS growth. These are all at constant exchange rate.
On a reported basis, our strong business performance, coupled with foreign exchange tailwinds, enable us to deliver reported revenue growth of 10.1%. That is despite a large gain of JPY 133 billion we booked as revenue in the first quarter of the last year related to the sale of the diabetes portfolio in Japan. Our business momentum remains strong and the significant upside we are seeing from foreign exchange has led us to raise our reported and core forecast and free cash flow outlook for the full year. Costa will share further details on this. The revenue growth in the first half of the year was driven by our growth and launch products, which delivered strong performance across our key business areas and grew 19% year-on-year at constant exchange rate.
ENTYVIO, TAKHZYRO and immunoglobulin each recorded double-digit growth of 17%, 31%, and 17%, respectively, in the first half of the fiscal year. We saw continued launch momentum from EXKIVITY and LIVTENCITY, demonstrating the strength of our commercial execution. We continue to see potential for further market growth and share expansion for ENTYVIO, and we are raising our peak sales estimate to a new range of $7.5-$9 billion. I will discuss this in more details in a moment. Earlier this month, we achieved a significant pipeline milestone when the CHMP recommended approval of our dengue vaccine candidate, TAK-003, for prevention of dengue disease. This came just two months after our vaccine's first approval in Indonesia. I will discuss QDENGA further on the next slide.
We also received a positive CHMP opinion for maribavir in relapse and refractory cytomegalovirus disease after a transplant. In both cases, we expect the European Commission to decide upon marketing authorization in the coming months. Most recently, we entered into a collaboration and licensing agreement with Zedira and Dr. Falk Pharma to develop TAK-227 for the treatment of celiac disease, an area of significant unmet need for patients. I would like now to focus on our dengue vaccines. The CHMP positive opinion for TAK-003 marked a major moment for Europe and the dengue endemic countries that participated in the EU-M4all procedure. It's also a critical moment for the global health community. Severe dengue is a leading cause of serious illness and death among children and adults in Latin America and Asia. The impact of dengue goes beyond just those who are infected.
There is often a significant economic burden on families supporting a hospitalized family member and an outbreak of dengue can overwhelm hospitals, causing a restriction in access to health care. The incidence of dengue has grown dramatically in recent decades, causing an estimated 390 million infections and half a million hospitalizations annually. Over half of the world population is at risk, according to the WHO, who have identified dengue as a top 10 threat to global health. Among the factors driving this rise in prevalence, the most critical ones are urbanization, globalization, and climate change. All in all, this speaks to the urgent need for a safe and effective vaccine for the prevention of dengue disease. With the approval in Indonesia and if approved by the European Commission, QDENGA will be a critical addition to the limited set of tools available to prevent dengue.
The result from our phase III clinical trial demonstrated long-term protection against dengue fever through four and a half years, with vaccines preventing 84% of hospitalized dengue cases and reducing cases of symptomatic dengue by 61% overall, with no important safety risk identified to date. The positive CHMP opinion is particularly encouraging because this is also the European Medicines Agency's first ever parallel assessment of a medicinal product for use in countries outside the EU, all eight of which are dengue endemic. What's very important here is that the CHMP recommended approval for broad use regardless of prior dengue exposure, which will make QDENGA the only dengue vaccine that does not require a blood test before administration, which we see as eliminating a critical barrier to access and increasing confidence about the efficacy and safety of the vaccines.
As I said, we expect the European Commission to make a decision on approval in the coming months with the dengue endemic countries to follow. Besides Europe, we received our first approval in Indonesia in August and expect to launch QDENGA there in early 2023. More filings are to come, with the U.S. filing expected within fiscal year 2022. In December, we will hold an investor event to dive deeper into our commercial strategy for this exciting vaccine. Moving to ENTYVIO, for which we are raising our peak sales outlook to $7.5 billion -$9 billion from the previous estimate of $5.5 billion -$6.5 billion. Since its launch in 2014, ENTYVIO has delivered outstanding growth momentum, and we are on track to exceed $5 billion in revenue this fiscal year.
ENTYVIO has established itself as a leading treatment option for IBD and is currently the number one prescribed biologic in bio-naive patients. Our confidence in raising peak sales reflect the continued expansion of the biologic market and a number of other factors related to the product. First, ENTYVIO has a depth of clinical data on real-world experience demonstrating its efficacy and safety. While we do expect there to be an increasing competition in IBD, we have yet to see any other product demonstrating superiority over existing biologic therapies. Second, ENTYVIO also continues to gain total patient share in various region and potential share gain are far from exhausted. As you can see from the chart, we continue to see an upward trend in market share in key regions.
In addition, we remain on track to file a subcutaneous formulation in the U.S. in fiscal year 2023, opening another pathway for growth. We will also continue to invest in further evidence generation to maximize the potential of the product. Finally, as we share, as we have shared previously, we have significantly extended our best-case timeline for when biosimilar are likely to be launched. At this stage, it is highly unlikely that we will see a biosimilar launch this decade, and it could be as late as 2032. In closing, this quarter demonstrated our growth strategy remains on track. We continue to deliver on our financial commitment to progress our pipeline and to create long-term value for our stakeholders while we fulfill our purpose of bringing better health for people and a brighter future for the world.
With that, I will turn the call over to Andy to update you on our pipeline. Thank you.
Thank you, Christophe, and hello to everybody on the call today. If we can go to the next slide 10, please, Chris. As Christophe just mentioned, we are extremely excited about the positive CHMP opinion supporting the broad use of QDENGA . We believe QDENGA is a transformative vaccine, fills a substantial unmet medical need for individuals in, and of course travelers too, warm weather climates. According to the World Health Organization, dengue is a top global threat that causes an estimated 500,000 hospitalizations each year. QDENGA has the potential to prevent morbidity and mortality from dengue in endemic regions around the world. As we've learned from COVID, a vaccine that protects against viral outbreaks and hospitalizations may also prevent local healthcare systems from being overwhelmed and unable to provide routine care.
This potential approval is the culmination of more than 10 years of successful research and development to produce a safe and effective vaccine against the dengue virus. After many years of thoughtful development, we were able to show an 84% reduction in hospitalization and no harmful effects four and a half years after vaccination. Moving to LIVTENCITY, which was approved in Canada and Australia for second-line post-transplant CMV disease this quarter. As Christophe just mentioned, we also received a positive CHMP opinion in September. We're looking forward to the near-term approval and launch in the EU. TAKHZYRO was filed in the U.S. for the prevention of HAE attacks in children two to 12 years of age. If approved, it would be the first and only prophylaxis treatment available for patients younger than six years of age.
We have one new clinical start this quarter for TAK-920, an antibody treatment for Alzheimer's disease targeting TREM2. This is the second experimental therapy to enter clinical development using Denali's blood-brain barrier transport vehicle-enabled technology. Lastly, we signed a licensing agreement with Dr. Falk Pharma and Zedira for TAK-227 in the U.S. and other territories outside of U.K. and Australia and China. TAK-227 is an oral tissue TG2 or transglutaminase 2 inhibitor with enriched activity in the intestines. The TG2 enzyme generates immunogenic gluten peptide fragments following the breakdown of gluten in the stomach and intestines. By inhibiting the body's immune response to gluten, it has been demonstrated to prevent mucosal damage in the small intestines. A phase IIA proof of concept study published in the New England Journal of Medicine demonstrated the protective effect of TAK-227 in patients undergoing a six-week gluten challenge.
TAK-227 showed very significant protective effects on the ratio of villous height to crypt depth in the duodenal mucosa, widely considered to be the most objective and valid endpoint in clinical studies for celiac disease. The trial also showed favorable effects of TAK-227 on a number of patient-reported outcomes. The program is currently in a phase IIB trial, testing three different doses and two dosing schedules over a 12-week period in celiac patients on gluten-free diet. This agreement to bring a phase IIB program with strong early data into our pipeline, complementing our portfolio of potential best-in-class therapies for moderate to severe celiac disease. Other programs include the potent short-acting oral glutenase TAK-062, with potential for mealtime dosing, and the systemically administered immune tolerizing nanoparticle, TAK-101. Let me tell you a little bit about celiac disease.
It has a global presence of about 1% of the population and no approved therapies. Maintaining a strict lifelong gluten-free diet is highly burdensome, and even with dietary modification, many patients continue to have persistent symptoms, small intestinal mucosal injury, and the potential for very severe secondary consequences, including malnutrition, cancer, diabetes, and even a higher mortality rate. If proven safe and effective, these investigational therapies have the potential to substantially benefit patients who continue to suffer from celiac disease despite dietary intervention. If we can move to slide 11, please. Shown here are 10 late-stage development programs, which continue to advance. As mentioned, we received a positive CHMP opinion for LIVTENCITY in second-line CMV disease and a positive CHMP opinion for QDENGA as part of the EU-M4all process.
We're on track to start a phase III trial for fazirsiran or TAK-999 by the end of our fiscal year. We continue to search externally for programs within our therapeutic areas and strategic focus that can add to our late-stage development pipeline and contribute to our marketed portfolio this decade. Next slide, please, Chris. We continue to be excited about our proof of concept readouts to come over the next one to two years. We plan to share updates on several of these programs, including TAK-861, the oral orexin 2 receptor agonist, by the end of the fiscal year. These are the first of many new molecular entities that could emerge from our rich and transformative early stage pipeline and add to our growing late-stage development programs. Next slide, please. Shown here are select expansion opportunities we have for our major P-brands.
We completed filing for TAKHZYRO for the prevention of hereditary angioedema in children based upon the outstanding data presented from the SPRING study at the European Academy of Allergy and Clinical Immunology this past summer. These data continue to illustrate the best-in-class efficacy and safety profile of TAKHZYRO, demonstrating 95% reductions in HAE attacks. We also filed CUVITRU for primary and secondary immune deficiency in Japan, continuing the product's global expansion. We are on track to soon file HYQVIA in the U.S. and EU as maintenance therapy for patients with CIDP based upon the positive results announced last quarter. If we can go to the next slide and my last slide, please. We have several key regulatory decisions and phase III study readouts expected this year. This quarter, QDENGA was approved in Indonesia with a broad label.
We also received a positive CHMP opinion recommending a broad label in the EU and in dengue endemic countries participating in the parallel EU Medicines for All procedure. We look forward to an EU decision in the coming months and additional regulatory reviews in dengue endemic countries in Latin America and Asia. We are on track to release the additional phase III readouts later this fiscal year. Thank you all very much, and I will now turn it over to Costa. Costa?
Thank you, Andy, and hello, everyone. This is Costa Saroukos speaking. Today I'd like to walk you through Takeda's fiscal 2022 first half financial highlights. Before that, I'd like to make a couple of high-level comments on our financial resilience in the current macro environment. Firstly, we have been delivering on our growth strategy, and our growth and launch products maintain strong momentum that we expect to carry on through the entry of Vyvanse generics next year and beyond. As Christophe detailed earlier, we are increasing our peak sales forecast for ENTYVIO to $7.5 billion-$9 billion. Next, we delivered year-over-year core margin improvement of over 2 percentage points despite the inflationary environment and despite emergence of VELCADE generics in May this year.
We have strong liquidity, and we have already locked in 98% of our debt at fixed rates with a weighted average interest rate of 2%. In fact, we'll pay off the final portion of floating debt in November. By next month, we will be at 100% fixed rates, meaning we are in a very favorable position within the current environment of increasing interest rates. Finally, FX has been a significant tailwind for Takeda this year, and we are upgrading our guidance to reflect this. I'll go through the details of this shortly. Now, turning to slide 16 in the financial highlights for the first half. Core revenue continues to deliver strong growth, up 5.5% versus prior year at constant exchange rate.
This was driven by growth in launch products such as ENTYVIO, TAKHZYRO and immunoglobulin, as we delivered growth in all geographic regions. We also continued to see steady uptake from the recent launches of LIVTENCITY and EXKIVITY in the U.S. Reported revenue growth was 10.1%, with business momentum and FX more than offsetting the impact of a JPY 133 billion gain from the sale of the Japan diabetes business that was booked in Q1 of the prior year. This one-time event is the only difference between reported and core revenue growth rates. The gain from the portfolio sale is also the main reason that reported operating profit for H1 declined on a year-on-year basis. Core operating profit, which excludes this gain, grew at 14.5% at a constant exchange rate to JPY 625.2 billion.
Our core operating profit margin was 31.7%, an increase of 2.4 percentage points on a year-over-year basis. This year-over-year margin boost is an indicator of our financial resilience and our ability to control costs. In fact, at constant exchange rate, our SG&A spend declined versus prior year. Net debt to adjusted EBITDA came down to 2.6x from 2.8x at the end of Q1, which means we are getting very close to our target of low twos. With regard to the full year guidance, we are reconfirming our constant exchange rate growth guidance while upgrading our reported and core and cash flow forecast primarily due to FX tailwind. Slide 17 shows our first half results in more detail. On the left-hand side, you can see the impact of the sale of the Japan diabetes portfolio last year on our reported growth rates, as well as our cash flow.
The impact of this one-time event on our growth rates will unwind over the rest of the year. For the full year, we are expecting double digit reported operating profit and reported EPS growth. Focusing on the core numbers on the right, I'm very pleased with the H1 growth we are delivering on a constant exchange rate basis. With revenue up 5.5%, core operating profit up 14.5%, and core EPS growth of 15.8%. In addition, foreign exchange has been a significant tailwind for us year-to-date, resulting in actual core EPS growth of close to 35%. Let me go into more detail on the H1 revenue performance versus prior year on slide 18.
On the left is a waterfall chart for reported revenue, which grew at 10.1% year-on-year, with business momentum and foreign exchange favorability more than offsetting the full impact of the JPY 133 billion one-off we booked in Q1 of last year from the sale of Japan diabetes portfolio. Core revenue, on the right-hand side, excludes the impact of the diabetes portfolio sale. As you can see, our business momentum was driving 5.5% growth at constant exchange rate, with the additional foreign exchange tailwind driving total core revenue growth of 18.9%. On slide 19, you can see that the key driver of top-line growth is our portfolio of growth and launch products.
Which generated JPY 759.8 billion or 38.5% of total revenue in H1, with 19% growth at constant exchange rate. Incrementally, these products added JPY 205 billion or $1.4 billion of revenue compared to the first half of last year. Within our five key business areas, GI, our largest area by revenue, grew at 12% year-to-date on a constant exchange rate basis. This was spearheaded by ENTYVIO, which grew at 17%, driven by a continued increase in bio-naive patient share. In rare diseases, which grew at 8%, we see continued demand growth and geographic expansion for TAKHZYRO, which delivered growth of 31%.
We also see early indicators of success with the LIVTENCITY launch, with 75% of transplant centers in the U.S. having now initiated therapy with at least one patient. PDT immunology continues to be very strong, with 14% growth, including 17% growth of immunoglobulin, fueled by strong global demand and enabled by steady supply. We have continued to expand our donation center network, adding 16 centers in the last six months, and we are on track to our guidance of 10%-20% increase in plasma donation volumes for the full year. We are also managing costs to improve margins over time. An average donor compensation in the U.S. is down by over 15% compared to the first half of fiscal 2021. Next, in oncology, which is declining year-on-year as expected, given that VELCADE generics entered the U.S. market from May this year.
Excluding VELCADE, the rest of the portfolio grew at 6% driven by ALUNBRIG, EXKIVITY, ADCETRIS, and ICLUSIG. Finally, neuroscience continues to perform very well, with growth of 11% driven by Vyvanse and TRINTELLIX. While the other segment is declining due to some regional loss of exclusivities in Japan. On slide 20, we show the drivers of reported and core operating profit for the quarter. Reported operating profit was JPY 255 billion, a decline of 26.3% versus prior year. Again, the decline is predominantly coming from the gain on the sale of the Japan diabetes portfolio, which contributed JPY 131.4 billion to reported operating profit last year.
We also had some one-off items impacting the other column here, such as impairment of intangible assets, which includes NATPARA and higher pre-launch ENTYVIO, and higher pre-launch inventory in preparation for future launches. As a reminder, the main impact on reported operating profit growth is due to the sale of the diabetes portfolio in Q1 of last year. This will unwind over the coming quarters, and we are forecasting for full-year reported operating profit growth of 15%. Core operating profit was JPY 625.2 billion, with our business momentum driving 14.5% growth at constant exchange rate and FX, an incremental tailwind driving total growth of 28.7%.
Slide 21 shows our free cash flow of JPY 296.9 billion for the first half, comfortably covering the half-year dividend payment and net interest paid, as well as the share buyback we completed in April this year. We closed September with ample cash of almost JPY 800 billion and total liquidity of JPY 1.4 trillion or close to $10 billion. Slide 22, the net debt balance is shown here compared to the end of March and demonstrates the continuation of our steady deleveraging progress from 2.8x down to 2.6x . The amount of debt on our balance sheet in Japanese yen terms increased over the period due to the depreciation of the yen versus the dollar and euro.
However, as a reminder, the depreciation of yen also benefited EBITDA, which means that the impact of FX on our leverage ratio is small. Also, we have structured the currency denomination of our debt to mirror our cash flow, which ensures that over time we'll be able to pay down debt without being impacted by FX movements. On slide 23, you can see our debt maturity ladder as of September. In addition to the $219 million of fiscal year 2022 debt that we paid in April, we also recently called $1 billion of debt maturing in fiscal year 2023 for prepayment this month. These payments were for USD denominated bonds with interest rates of 3.6% and 4.4% respectively, allowing us to further optimize our debt profile.
We are on track towards our plan of paying off approximately JPY 500 billion of debt this fiscal year, targeting higher than average interest debt. As a reminder, our current weighted average interest rate is approximately 2%. Importantly, 98% of our total debt is at fixed interest rates. By November 2022, we expect our debt to be at 100% fixed rates. This puts us in a very strong position in the current macro environment of rising interest rates. Finally, I'd like to point out that we've had some positive changes in our recent credit ratings with both JCR and R&I upgrading our ratings recently.
Next to slide 24, where we reconfirm our full year management guidance for growth at constant exchange rate, with core revenue growing at low single-digit and core operating profit and core EPS growing at high single-digit. For our reported and core forecast, we are upgrading our numbers primarily to reflect FX tailwinds. On a reported basis, we increase our revenue forecast to JPY 3.93 trillion, operating profit to JPY 530 billion, and EPS to JPY 198, with strong growth rates versus prior year. On a core basis, revenue is expected to be JPY 3.93 trillion, with core operating profit now expecting to reach JPY 1.18 trillion and core EPS to reach JPY 525.
This represents growth of approximately 15% for core revenue and 23% for core operating profit and core EPS. This upgrade is based on FX rate assumptions using the first half average FX rates, specifically 132 yen to the U.S. dollar and 138 yen to the euro. Finally, we are also increasing our outlook for free cash flow from JPY 600 billion - JPY 700 billion now to JPY 650 billion-JPY 750 billion, primarily reflecting the FX benefit. We also remain fully committed to our full year dividend of JPY 180 per share. To close out the presentation on slide 25, I'd like to re-emphasize the key elements of our strategy to deliver sustainable growth and value for shareholders.
We continue to see strong momentum from our commercial portfolio, which enabled us to deliver 5.5% core revenue growth at constant exchange rate in the first half of this fiscal year. This is driven predominantly by our growth in launch products growing at 19% on a CER basis, more than offsetting the impact of generic versions of VELCADE in May 2022. Our margins are strong, with 31.7% core operating profit margin in H1, and we delivered core operating profit growth of 14.5% at constant exchange rate, well on track towards our full-year guidance of high single-digit growth. Our success is built on a solid financial foundation with robust cash flow that we will continue to allocate towards growth opportunities, continued deleveraging, and competitive shareholder returns.
We have abundant liquidity and a well-structured debt profile of 98% fixed rates at an average cost of 2%, which positions us well in the changing macro environment. Finally, before we open it up to Q&A, I would like to bring to your attention an upcoming investor call we have scheduled for mid-December, focusing on our launch plans and commercial strategy for QDENGA. We look forward to your participation in this event. With that, I'd like to open it up for Q&A. Thank you very much.
Now, I would like to take your questions. In addition to Christophe, Andy and Costa, the management team, which you can see on the slide, is also present to take your questions. If you'd like to ask a question, please let us know by clicking on the Zoom Raise Your Hand button. We'll take your questions in turn. If you are selecting Japanese, please ask your questions in Japanese. If you are selecting English, please ask your questions in English. If you have the interpreter function turned off and are listening to the live audio, you can ask questions in either language. Please make sure that you ask all the questions first. Now I'd like to take the first questions. From Citi, Yamaguchi-san. Please unmute yourself and ask your questions.
Can you hear me okay? I am Yamaguchi.
Yes, we can hear you well.
I have two questions. First question is for this quarter. You are doing very well. Next quarter, Vyvanse patent cliff is going to be something you're facing, but new products are doing well. For the next fiscal year, your revenue is going to be more or less flat, but your profit is going to come down according to your guidance. Is there any updated guidance? That's my first question. The second question is about TAK-861. By the end of this fiscal year, you are going to obtain POC. That's been confirmed. Is there any latest update whether the study is going well and if you'll be able to obtain POC before the end of this fiscal year? Can you comment on that?
Thank you very much.
First question, Costa Saroukos, please respond. Then the second question, about orexin program, Andy, please respond.
Great. Thank you very much, Yamaguchi-san, for your question. First, let me just say that I'm very pleased with our first half results for fiscal year 2022. We're showing very strong growth, as you mentioned, on the growth and launch products, growing at 19%. This generated $1.4 billion in revenue for the first half of the year. With this projection and continuation of growth, as you mentioned, we feel like this could potentially offset the impact next year of Vyvanse loss of exclusivity. Just as a reminder, Vyvanse loss of exclusivity is more targeted around August, so you don't have the full impact, not the full 12 months impact there. Having said that, on the margin side, we are looking at managing our margins accordingly.
The growth and launch products is also high margin products overall. They have higher margin than the total company. Then, of course, on the OpEx standpoint, we will continue to stay very laser focused on managing our OpEx to ensure that we have a sustainable operating profit margin. We'll give you more information in May when we give our guidance, but directionally, we are, you know, feeling pretty solid about this year and also with the trajectory of our growth and launch products next year and our cost management. I think this is something that we can manage the overall operating profit margin. We'll give you more information in May of next year when we give our 2023 guidance.
Yamaguchi-san, this is Andy. Thank you for your question on TAK-861. Yes, the study is going very well. This is our phase I, phase IB study. We're currently in the process of enrolling and evaluating patients with type 1 narcolepsy with four weeks of treatment with TAK-861. We know TAK-861 is an active molecule. We've looked at sleep-deprived healthy volunteers. The key questions for us are the overall profile, and we're looking at a number of endpoints in this study. The 40-minute maintenance of wakefulness test. We're looking at sleepiness indices, and we're looking at a number of different parameters. We're also very conscious of dose, and we're trying to understand where that optimal dose range is going to be for TAK-861.
We're planning at risk to begin a phase IIB study later this year. We're waiting now for the totality of data to come in, and we'll have all of those data to support that decision by the end of the fiscal year. Thank you.
Thank you. Next question is, Stacy Ku from Cowen. Please.
Hi. Stacy Ku from Cowen. Thanks for taking our questions and congratulations on the progress. So first question is, as you continue to nicely deleverage, can you expand some more on the potential strategy for business development? Which core therapeutic areas are you identifying opportunities? And maybe clarify the potential phase and development and potential size of the opportunity. That's the first question. Then for ENTYVIO, as we approach 2023, wanted to confirm if the subcutaneous offering is still on track. Do we expect filing for both UC and CD? And does the updated guidance include subcutaneous contribution in 2024? Then last, kind of another follow-up on ENTYVIO. Just can you provide some additional details between the potential key drivers between the high end and the low end of the peak sales?
There are a few moving pieces, so is it the competition that we should be considering when we look at this wide range, or is it more the potential impact from biosimilar entry? Any additional details would be appreciated. Thank you very much.
Thank you, Stacy. The first question about the business development, Christophe, could you please take it? The second and third question about ENTYVIO, Ramona, could you please respond?
Yes. Thank you, Stacy. It's Christophe. On the BD front, we want to enrich our pipeline. The first thing is that we are not looking for large M&A. We have the scale we need. We are global. We can compete in every key market. By the way, QDENGA is a vaccine that we can launch by ourselves because we have such a strong presence in countries which are endemic. It's a good example of how you combine innovation and globalization, and how you can launch a global product. We do seek to enrich our pipeline. We have, you know, 40 products in development in the pipeline, but we know that not all of them will make it. We are looking at enriching our pipeline.
We are looking at assets which are in mid, late stage, let's say asset that could be launched before end of the decade. We are focusing on our core therapy area. Sometimes if there is adjacency, we could look at it as well, but that's mainly where we are looking at. You have seen our cash flow. Very soon we'll be in the low 20s, so we have some firepower, if you like, to do this type of very targeted business development. But it's really asset by asset. We're not, again, we are not looking at scale. We are looking at quality assets.
Thank you, Stacy, for your question. It's Ramona here. Let me answer your questions about ENTYVIO . First of all, absolutely, the subcutaneous form is still very much on track to be filed in FY 2023, as we've previously disclosed. We're confident that we have the package to be able to file that. We're excited, actually, looking forward to bringing the subQ to the U.S. market. On the range that we provided for ENTYVIO , you know, in the situation where we were not to get a subQ in the U.S., certainly that would put us towards the lower end of the range. As all of our projections are on track, you would expect us to be more in the mid or mid to higher level of the range.
The reason for the range is, as you said, the competition. You know, depending on how standard of practice changes with the number of new molecules coming into the market, it's very difficult to project now five, six, seven, eight years out. We're giving ourselves a range to be able to do that. We're, you know, everything we're seeing right now in the market, even with new products coming on board, is that ENTYVIO is just more and more being solidified as a safe, effective first-line foundational therapy for IBD. We feel very positive about all of the underlying trends we're seeing, even with new products entering the market. Thank you.
Thank you very much.
Thank you, Stacy.
Moving on to the next question. Nomura Securities, Kotani-san. Please unmute yourself and ask your question.
This is Kotani from Nomura, Tokyo. Can you hear me? Can I ask this question in English?
Yes, of course.
Okay. I have three points. One, when I look at page 38 of the financial document, I find that ALUNBRIG has failed the ALTA-3 trial, which obviously was the head-to-head comparison versus alectinib as the leader in ALK-positive NSCLC. My understanding is that this was the largest and last trial for ALUNBRIG to really expand its sales potential, yet it doesn't really seem like Takeda has impaired this asset. Is there a possibility that ALUNBRIG could meet your high expectations with that ALTA-3? That's number one. Number two, I think the really good news in Q2 was Takhzyro growing really strongly in the U.S. again, with I think yen-based 75.5% growth in the U.S. in Q2. I think in the first quarter, the growth was quite limited, and constant currency-wise, it was very small.
We were a bit concerned about the unexpected share gain of ORLADEYO, the oral drug from BioCryst. Could you share with us what you're seeing on the ground in terms of TAKHZYRO? Are you seeing a reversal of the patients from ORLADEYO after having HAE attacks or side effects? The third point is, can you talk about your view on 2024? Because Vyvanse expires in August 2023, there is a sizable impact on 2024 also. I think even with the revised forecast, 2023 is probably likely to show a decline in core OP. Now if 2024 is also going to show a decline in core OP, that's problematic. If you could share with us your view on 2024. That's it for me.
Thank you, Kotani-san. First question about the ALUNBRIG ALTA study, Teresa, could you please take it? The second question regarding TAKHZYRO and then the competitive situation, Ramona, could you please respond? The last question about the you know 2023 and the 2024 outlook, could you, Costa, could you please take it? Thank you.
Hi, this is Teresa Bitetti responding here. You are right about the ALTA-3 trial. You know, what we've found is that ALUNBRIG-.
Continues to deliver strong year-over-year results, driven by what we've seen as growth in EUCAN and Japan, as well as in our growth in emerging markets. We're continuing to focus our efforts. Even without the head-to-head trial, we're focusing our efforts in the first line setting, where it's clear that there's strong benefit for ALUNBRIG, which includes the overall, you know, improved intracranial efficacy, long-term tolerability, dosing impact, and quality of life, that are really meeting the needs of patients. There's still a lot of growth in this product, and we're gonna continue to focus our efforts there.
Hi, Kotani-san, it's Julie Kim. I'm going to take your TAKHZYRO question because I believe you're asking more about the dynamics in the U.S. market. For TAKHZYRO, we are seeing good growth, good market demand for TAKHZYRO. We continue to believe in the strong efficacy profile that TAKHZYRO provides for patients, and we're seeing that in terms of the resurgence in demand. From a market dynamic standpoint, while anecdotally, we are seeing some patients who have started on oral come back to TAKHZYRO because of the efficacy profile that we have. There isn't anything specific that we would comment on that beyond the anecdotal evidence that we have seen. From an execution standpoint, what I would comment on is that we've been working very hard on, let's say, eliminating friction in the system.
There are quite a lot of hurdles that patients still need to go through to get on therapy once they are diagnosed. Some of that resurgence in demand, we believe is because of our efforts in terms of, as I said, eliminating friction in the system to allow patients to have access to therapy much faster. Thank you.
Thank you, Kotani-san, for your question. Let me just, without giving guidance for fiscal year 2024, give you some key pushes and pulls here. Firstly, the Vyvanse impact will be more heavily weighted in 2023, for sure. There will be some carry over in 2024, but the majority as a proportion will be impacting us in 2023. For 2024, the impact overall for loss of exclusivity will be much less than what we've experienced in fiscal year 2023 and also in 2022. Overall, the LOE in 2024 will be much lower. On the flip side, on the top line revenue, we continue to see growth of our growth and launch products accelerating. We have acute dengue launching as well, and that will still also continue to drive some top line revenue growth.
Finally, on the OPEX, we'll continue to manage G&A, SG&A, OPEX. We'll continue to improve our PDT profitability. You saw that, this year and last year, we've had some dynamics, market dynamics, which has increased overall donor fees, but that's starting to, as you saw in Q2, year to date, our donor fees have started to come down by more than 15% versus prior year. We expect improvements in PDT profitability as well.
Thank you.
Now, there was a question on the ALUNBRIG impairment. We do regular tests as well every year and every planning cycle. We still have a buffer here on ALUNBRIG. It's not just on revenue, but it's the overall cash flow NPV versus the purchase price. You know, we get this assessed on a regular basis by our external auditors, and thus far, we have not triggered any impairments. Thank you very much, Kotani-san, for your question.
Thank you for your question. Next question is from Morgan Stanley Securities, Muraoka-san. Please unmute.
Good afternoon. I am Muraoka from Morgan Stanley. Do you hear me okay?
Yes.
Thank you. My first question is about shareholders' returns. Leverage has come down and your performance is quite good, so probably you can start thinking about increasing your dividend. It's actually high time for you to think about it. Any comments, including the timing of doing that? What's your thought on that? That's my first question. The second question, new, two new products, LIVTENCITY and EXKIVITY. During the first quarter, their growth looked very well. During the second quarter, if I look at the numbers quarter-on-quarter, it looks like the growth rates are flat. What's the background? Is this a slowing down or is this just a transient situation? Can you give me some background of that? That's all from me.
Thank you, Muraoka-san. The first question about the shareholders' return, Costa, could you please take it? The second question about the EXKIVITY's uptake, Teresa, please respond. The third question about the LIVTENCITY's performance, Ramona or Julie, could you please respond? Thank you.
Yes. Thank you, Muraoka-san, for your question. It's a great question, and it's definitely something we're looking at in particular as we continue to deleverage. You know, we've promised as part of the capital allocation policy to deleverage rapidly and to get down to the low 2x . We're on track to delivering that target. You saw already in Q2 year-to-date, we've gone. We're down to 2.6x . We're still not there. We're still not at low 2x . I'm confident that we're gonna get there and potentially even get there faster than our original committed timeline of fiscal year 2023. Once we close this, we'll get. We have a lot more firepower, a lot more cash flow. Our free cash flow continues to grow.
Of course, we will look at reducing the number of capital allocation drivers. Today, we have three. It's investing in our growth drivers, deleveraging rapidly, and shareholder returns. Once we deleverage down to the low twos, we'll have two areas of focus. One being continuation of investing for growth, which could be also, as Christophe alluded to, acceleration of, you know, acquisitions, later stage acquisitions for growth, continue to invest in R&D, both in-house and partnerships, continue to invest in new product launches. The second one is obviously the shareholder returns. Look, perhaps dividend increases could be definitely on the cards there. Thank you very much, Muraoka-san, for your question, and we are looking into it. Thank you.
Muraoka-san, this is Julie Kim. I can take your question on LIVTENCITY, and then I'll pass to Teresa for EXKIVITY. In terms of LIVTENCITY, we're very very excited about the treatment option that this provides for individuals with refractory CMV, as there really wasn't a treatment available to them. What we are seeing in terms of the growth that you pointed out is not a new trend per se. Transplant is an acute situation. It is an event that happens, so it's very hard to predict when patients will need LIVTENCITY as a treatment. What we are very encouraged by is the fact that we have over 90% of our patients receiving full course of therapy. We have very high coverage, over 90%, coverage from a reimbursement standpoint.
We have over 80% of the centers now treating patients with LIVTENCITY. There's still opportunity for growth, and we expect LIVTENCITY to continue to do well. Teresa?
Yep. Thank you. This is Teresa Bitetti. Thanks for the question on EXKIVITY. We continue to be pleased with results of EXKIVITY's launch in the U.S. market. The data shows that EXKIVITY continues to capture half of all new patient starts among the two branded EGFR exon 20 treatment options that are there. We continue to see the increased potential for more growth. We do see an opportunity to increase duration of therapy, so we are working with physicians to make sure that we educate very clearly on side effect management, dosing, and the importance of the duration of that therapy. You know, there is no change to our growth forecast at the moment.
I mean, we'll continue to keep an eye on that and keep you updated, as we gain more and more insights, as we continue to launch EXKIVITY. Thank you.
Thank you, Muraoka-san. Next question is, JP Morgan, Wakao-san. Please unmute.
This is Wakao, JP Morgan. Thank you very much. I have two questions. First is ENTYVIO peak sales increase. In page 12, you listed up several factors for this upgrade. Which one is the biggest factor? The top is the ones most important, meaning biosimilar entry is not now expected until 2032. Is that the biggest reason? Looking at the current situation, ENTYVIO share seems to be very close to the peak. Do you think that as market grows, then ENTYVIO sales will also grow? Next is about 861. Regarding the 861, whether to continue the study or not, I think you will make a decision within this year. That's what I heard.
Now I think it's shifted to, by the end of, March. Does that mean that, you need, to take longer time to make a decision? Also, what about the safety profile of eight six one? I think that you seems to be more careful than myself. The, required criteria of safety for eight six one, is it now, higher or severer? The other compounds, moving on to phase II, compared to those cases, do you think that, eight six one's hurdle to move on to the next phase is higher? Wakao-san, thank you very much.
Question about ENTYVIO peak sales revenue. Ramona, could you please take it? The second question about the TAK-861, Andy, could you please respond? Thank you.
Yes. Thank you, Wakao-san. Let me answer your question on ENTYVIO peak sales. You're correct. The major driver of the increased peak sales is basically the increased time on market that allows us to continue to take advantage of the positive trends and grow. That's what's driving the increased sales. We have a number of positive trends which include, as I mentioned, continued growth in share and continued growth in first-line therapy. We're seeing continued growth of the IBD market, and we expect the subcutaneous to be coming in the U.S. as well. Certainly we do see, you know, more competitors entering the marketplace, so that would be a bit of a headwind. We feel confident in our new peak sales estimate given the positive trends in our favor and the extended time we have with ENTYVIO.
Thank you.
On 861, this is Andy. On 861, Wakao-san, we're moving forward the program in an accelerated fashion and it is entirely on track. The intent to start a phase IIB study at the end of this fiscal year is very much in line with what we communicated and signaled at the beginning of the year. With respect to safety, we're. As I said, this is a very accelerated program and we're balancing the potential to bring forward a transformative therapy for patients with narcolepsy with while ensuring that we're doing everything we can to guarantee patient safety. We're being very thoughtful in how we make and drive decisions given the experience with TAK-994.
You know, we remain extremely excited about the mechanism and over the next couple of months we'll have a full data set on TAK-861 that'll allow us to make a decision as to whether we move forward or not.
Hi. Arigatou gozaimasu.
Thank you. Thank you very much, Wakao-san. Next question, Credit Suisse Securities, Sakai-san. Please unmute your microphone and ask your question.
This is Sakai with Credit Suisse. First question to Costa. You made an upward revision. On page 20, core profit margin for the first half. There was a JPY 69.1 billion factor from FX. For full year it's JPY 800 billion. I understand that Forex was taken into account. Supplement A sixteen shows the sensitivity for exchange rate. You have some assumptions there. For the full year, 132. This is not much different from the first half, 131. Based on that you came up with this, JPY 800 billion yen. In terms of a core margin, maybe the margin would go down. That's my question. How did you calculate that? What is the formula?
Can you please explain how you calculated these numbers? That's my first question. Another question is for Andy. Orexin phase IB study that's been mentioned before. This is phase IB, so there is no blinding. Healthy volunteers, the subjects, I'm sure that you have seen the raw data to a great extent. Based on all the data you have seen already, you don't see any safety signals. Is that a correct understanding? Those are the two questions.
Thank you, Sakai-san. Let Costa take the first question around the upgrade guidance. Then also Andy around the orexin program. Could you please respond? Thank you.
Yes. Thank you, Sakai-san, for your question. If you look at that slide A16 in the appendix, you're right. You know, we have the new U.S. dollar Japanese yen 132 for the full year assumption now. Year to date, it's, you know, what we actually saw was 131. The way we calculated the overall future exchange for the U.S. and euro was we used the year to date average. Okay? 132 for the USD and 138 for euro. Now we don't see any major impact on the operating profit because of this.
Overall, you know, the COP margin is quite neutral overall to the company because of the product mix and also the cost base that we have. Now on, you know, we saw that September, the U.S. dollar was 144. The yen to the U.S. dollar was 144. Now if that continues for the rest of the year, we do have further upside. At this stage it's very hard to predict what the full year impact will be on FX. If it is around 144, we have further upside to our core revenue, our core operating profit and our core EPS.
The upside if it was similar to what we saw in September of 144 yen to the U.S. dollar, it would be an upside, incremental upside of about 3% on the core revenue, around 4% on-.
On the operating profit and approximately 5% on the core EPS. That gives you a sort of a broad understanding, but no impact to the margin. Thank you, Sakai, for your question.
Sakai-san, you're correct. The phase IB portion of the study is that doesn't have a comparator arm. It's just an active arm. In the blinded data to date, you know, remember, it's four weeks of dosing, but in the blinded data to date, we don't see any signal to suggest any liver safety issues so far.
Thank you.
Thank you. Thank you, Sakai-san. Next question is from Goldman Sachs, Ueda-san. Please unmute yourself.
Hi, I'm Ueda from Goldman Sachs. I have two questions. First, going forward, R&D strategy update. When are you going to disclose your updated R&D strategy? Last year, you had explanation meeting for wave one, giving us outlook for each one of the products in wave one. But since then, I'm sure that there have been a lot of updates. Therefore, as of right now, what is the renewed outlook of R&D strategy and what is the potential you are looking at for each product and when are you going to update us on that? What is the timing for that? TAK-861 before the end of this fiscal year, you'll be able to have the data, and after that, probably you can give us an update. So it's going to be early next year that you can update us on that?
The second question is about PDT, about the donor fee development, page 34. Right now, the donor fee is coming down. You are showing that on that page. As of now, the current level compared to the pre-COVID time before the donor fee went up, how do you compare the current level compared to the pre-pandemic level? This declining trend, is it going to continue?
First question about the next R&D day expected. Christophe, could you please respond to this question? Then the second question around the donor fee, Giles, could you please respond? Thank you.
Yes. Thank you, Ueda-san. You know, we first update about our pipeline at every quarter, so we keep you updated. We will organize an R&D day as soon as we will have enough new events, new readout. Either it will be in fiscal year 2022 or at the beginning of 2023. We have not decided a date yet.
This is Giles speaking. As Christophe mentioned, we have been able to reduce year-on-year our donor compensation by upwards of 15% for the first half of fiscal 2022. We continue to monitor market dynamics closely as we need to strike the right balance between collecting enough plasma to meet our commitments to patients and of course, improving margins. Our ability to continue on this trajectory will be contingent on market dynamics. Thank you for the question.
Ueda-san. Ueda-san, thank you very much. We'd like to move on to the next question. Next is Mitsubishi UFJ Morgan Stanley. Kumagai-san, please.
This is Kumagai, Mitsubishi UFJ Morgan Stanley. Can you hear me? Yes. Thank you. I have two questions. One is about the QDENGA. About your pricing strategy, I'd like to hear more. I think it depends probably on country. What is your view about the pricing? Second is two-two-seven. It is a very interesting molecule, I think. What's your future development program over two-two-seven, as much as you can disclose. Thank you.
Thank you, Kumagai-san. The first question about the QDENGA pricing strategies, Ramona, could you please take this question? Then the next question about the TAK-227, the celiac disease, Andy, could you please respond? Thank you.
Yes. Thank you very much, Kumagai-san. I would like to take the question on QDENGA pricing. First of all, let me remind you that dengue is endemic in over 100 countries. Many of these are some of the most populous countries in the world. As we bring this vaccine out globally, we wanna make sure that it's accessible to all of the patients who need it, both in private and in public markets, in travel markets and in endemic markets. What we're doing with dengue is we're going to be coming out with a tiered pricing strategy so that we can segment markets based on healthcare sophistication, and make sure that it becomes available to the patients who need it.
We are having a dengue and investor relations day on December fifteenth, and at that time, we will be sharing more about our launch plans and would very much enjoy you attending that, please. Thank you.
Thank you very much for the question on TAK-227. We're extremely excited about this mechanism. It's easily the most compelling program to emerge in the celiac space now and really ever. It's working through a very unique mechanism in the intestine where it prevents the ability of the immune system to recognize gluten. It's an enzyme that modifies the gluten fragments, so that they can't be presented to our immune system. That mechanistic hypothesis played out in a phase II study that was published in the New England Journal of Medicine last year. I encourage you to seek out that article because it's incredibly compelling. Benefits on multiple pathological endpoints and the suggestion of significant benefits to patient symptoms. It's a really exciting molecule. Right now, our partners at Dr. Falk Pharma.
Falk Pharma and Takeda are running a phase IIB study. It's a 12-week study in patients on a gluten-free diet. It's actually a different design than the phase IIA study, which was a gluten challenge study. We looked at intestinal pathology and symptoms in response to gluten that was given to patients during the study. The phase IIB study will just look at patients living their normal lives avoiding gluten, so it's more of a real-life scenario. At the completion of the phase IIB study, Takeda will take control of the global phase III study. The FDA has just released a guidance that provides great clarity on what's necessary for an approval in celiac disease.
We'll need both histological and patient-reported outcomes, both of which we've seen benefits on in our phase IIA study, and it will be a one-year study in duration. We have a tremendous clarity in terms of that plan. Even before we finalized the deal, we started to work together closely with our partners to build that strategy so we could accelerate it.
Understood very well. Thank you very much.
Thank you, Kumagai-san. Next question from Miki Sogi-san from Bernstein. Please unmute yourself and ask your question.
Thank you very much for the opportunity to ask questions. I have two questions. First question is around PDT cost. We understand that you have been presenting the declining of the patient donation fee that should impact the PDT products at the cost. Please help us understand what kind of the degree of impact that is coming from the donation fee to the cost of the PDT. Also, what are the other, you know, the key factor that that also impact to PDT costs? How much eventually are you expecting to decrease the costs overall for PDT?
The second question is around the operating profit of this year. We understand that you have just reported that the reported operating profit year-over-year growth was actually declined by 26%. You're projecting that it will end the year with a 15% growth year-over-year. What would be the key driver to such a strong finish for the operating profit? Those are the two questions.
Miki Sogi-san, I'm sorry, but we cannot really hear you very well. Could you please ask the second question once again?
Yes. The second question is around operating profit. Hope you can hear me.
Not enough yet. Could you please, you know, get closer to the microphone or.
Can you hear me?
Barely.
Can you hear me?
Yes, we can hear you very well.
Oh, great.
Repeat the second question. Thank you.
Thank you very much. The second question is around operating profit. You have reported that the first half of the operating profit was the growth for the operating profit for the first half of the year was -26%. You're projecting that you will end the year with the reported operating profit with the 15% growth year-over-year. I was just wondering, you know, what is the key assumptions to make such a strong finish by the end of the year?
Thank you very much, Miki Sogi-san. The first question around the donor piece and then also the impact to the costs to the PDT business. Giles, could you please take it? Then also the next question around the operating profit, Costa, could you please respond? Thank you.
Yeah. Thank you for the question. This is Giles again. Absolutely right. We have been successfully bringing down donor compensation levels, albeit still above pre-pandemic level, but upwards of 15% reduction in the first half of fiscal 2022. All the while, you know, maintaining our collection volumes above pre-pandemic levels for the past 18 months, and we're the only one of the top three companies to be able to achieve that. We do expect that trajectory to continue. Of course, that will depend on market dynamics, and there are other factors as well that give us confidence that we can continue to improve our margins over time. A continued focus on innovation, and you will have heard from Costa.
That our immunoglobulin portfolio grew 17% while our SCIG portfolio actually grew 19%. That focus on innovation with CUVITRU and HYQVIA are continuing to increase contribution of our innovative IG portfolio. The SCIG portfolio now represents 26% of total immunoglobulin revenues, and increasing over time. The other thing is continued focus on productivity and efficiency improvement right across the value chain from collection through fractionation, purification, distribution. That's helping to improve our margins over time as well. Thank you for the question.
Yes. Hi, Sogi-san. Thanks for the question. If I understood correctly, 'cause you were breaking up, you just wanted to understand the reported operating profit growth for the full year guidance versus the first half of the year. Again, the main reason for the decline is coming from the one-off gain on the sale of the Japan diabetes portfolio last year in Q1. Every quarter that goes by, this gain from Q1 will unwind. For example, if you look at our Q1 reported operating profit, that was declining close to 40%. Now in Q2, it's declining at -26%. Every quarter, that gap will start to come down.
You'll start to see the impact of that quarter one of last year gain of, for the sale of the diabetes portfolio, 'cause it's a one-time event. It'll unwind for the full year. That's something that you just need to keep an eye on. Thanks very much.
Thank you very much.
Thank you, Sogi-san. Now, next question is going to be the last question. We would like to conclude with the next question. The next question is from Nikkei BP, Hashimoto-san. Please unmute yourself.
I'm Hashimoto from Nikkei BP. Do you hear me okay?
Yes.
I have two questions. First, about dengue vaccine. This is going to be the first global vaccine with high expectations. I do understand that, but it's taken 10 years. Why is it that it's taken so long? For any global vaccine, is that the normal timeline, or is it because of the difficulty specifically with dengue vaccine? Nuvaxovid, another vaccine. Omicron variant product is being developed by Novavax, and they are going to file in the fourth quarter in Japan for Omicron variants Nuvaxovid. Are you going to develop that for Omicron variants as well?
Thank you very much for your question.
Christophe, could you please take the first question around, you know, the QDENGA development history, and then the second question around the Nuvaxovid Omicron specific vaccine? Masato, could you please take it? Thank you.
Yes. Thank you, Hashimoto-san, for the question. 10 years, but you need to understand that we generated four and a half years efficacy data. Half, in fact, half of the 10 years, it's about conducting the clinical trial and generating this four and a half years. I think that's very important. That depends by disease, by vaccines. Normally it's very important to have long-term efficacy data. There was an exception made for COVID vaccines, frankly. Where, you know, because of the crisis, the world was satisfied with six months, but that's the exception. Normally, you need more long-term efficacy data. That's what we generated. Four and a half years is quite long. It's quite long.
That just explain why it took overall 10 years to generate these vaccines. Dengue is also very complicated because you have multiple serotype, and this is the infection gets more severe when you get more exposure. It's actually a very tricky disease to protect against, and that's why we are so pleased with the result that we generated with these vaccines. Thank you.
This is Iwasaki speaking. Thank you very much for your question, Hashimoto-san. Yes, we have been able to bring two vaccines to Japan to respond to the pandemic situation. We are contributing to the public health of this country. We are very proud of it, and we have a very strong sense of mission. About Nuvaxovid Omicron variant vaccines, as you have said at the outset of your question, overseas, outside of Japan, Novavax is developing or considering developing Nuvaxovid for Omicron variants, according to some reports. As of now, in Japan, we don't have anything that we can disclose. We will continue to monitor Novavax situation overseas, and we will have continued close cooperation and communication with PMDA and MHLW to consider whether we should be also developing Nuvaxovid for Omicron variants or not.
Thank you very much, Hashimoto-san. With this, we conclude the conference call for today. Thank you very much for taking time out of your busy schedule to attend today. If you have any individual questions, please contact our IR office. We look forward to your continued support. With this, we conclude the webinar. Thank you.