Commentary and statements during the call regarding among other topics, the proposed acquisition of Biohaven by Pfizer and Biohaven's and Pfizer's pipelines, in-line products and product candidates, which are subject to risks and uncertainties. Additional information regarding forward-looking statements is available under Risk Factors and Forward-Looking Information, and factors that may affect future results in our SEC filings on forms 10-K and 10-Q, and in the press release we issued this morning. Forward-looking statements on the call speak only as of the call's original date, and we undertake no obligation to update or revise any of the statements. Joining us for the call today are Dave Denton, Pfizer's Chief Financial Officer, Angela Hwang, Group President, Pfizer Biopharmaceuticals Group, Aamir Malik, Chief Business and Innovation Officer, and Vlad Coric, Chief Executive Officer of Biohaven.
Also joining us for the Q&A session will be Pfizer's Internal Medicine Leadership Team, including Global President Nick Lagunowich, Chief Development Officer Jim Rusnak, and Chief Sci-
The acquisition gives Pfizer's access to the premium products serving the large and growing unmet patient needs in the global migraine market. Recall that Biohaven has developed the first and the only breakthrough medication to both treat and prevent migraines. Coupled with Pfizer's best-in-class primary care footprint and our highly experienced field infrastructure, we see the potential for annual global peak revenues in excess of $6 billion annually. Further, the acquisition is forecasted to not only drive incremental revenues in the 2025 to 2030 timeframe, but is also forecasted to enhance the company's financial returns. Biohaven is a company we've known well and we admired, recently taking the relationship to a new level in collaborating with them on the ex-US rights to their migraine portfolio late last year. This proposed transaction represents significant value for both Biohaven and Pfizer shareholders.
With the price of $148.50 per share for a total cash consideration for Biohaven's equity of approximately $11.6 billion. Excluding shares already owned by Pfizer, the purchase price represents a 33% premium over the 90-day weighted average trading price. Immediately prior to closing the transaction, Biohaven's non-migraine neuroscience assets and related personnel, along with $275 million in cash, will be spun off into a new publicly traded biopharmaceutical company owned by Biohaven's current shareholders. Pfizer will retain all the commercial migraine assets as well as all the late-stage pipeline and early-stage compounds related to the migraine franchise. I should note that this transaction is subject to the completion of the spin-off and customary closing conditions, including the receipt of regulatory approvals and the approval of Biohaven shareholders.
We expect the transaction to close by early 2023. Now with that, let me turn it over to Angela to delve more deeply into the transaction rationale.
Thanks, Dave. This transaction is great for patients, Biohaven, and Pfizer. Pfizer's purpose is to deliver breakthroughs that change patients' lives, and we see this as an opportunity to help address this challenge for more than 1 billion patients around the world suffering from debilitating migraines. Nurtec's differentiating profile meets the needs of patients suffering from both acute and episodic migraines, giving patients and healthcare professionals an option that has not existed before. This new business is also a strong strategic fit for Pfizer and our internal medicine business unit. We have a strong legacy in pain and women's health, a best-in-class commercial organization, including a top-ranked sales, account management, and marketing team who have been at the core of creating blockbuster brands such as Eliquis, Lipitor, Lyrica, Viagra, just to name a few.
Our scale allows us to operate in over 125 markets around the world. With this acquisition, we can build global teams across all markets to ensure the success of this new migraine franchise. We are already actively planning for potential launches in 70 countries, and we're engaged with health authorities in these countries to enable successful launches subject to regulatory approval. This transaction is also good for Pfizer shareholders because we expect to create value beyond the premium that we're already paying for Biohaven. To accomplish this, we plan to build off the great work done by Biohaven and bring the scale and expertise of the Pfizer commercial engine to maximize the opportunities for patients and our new migraine franchise.
We're planning to combine the best of Biohaven with Pfizer's go-to-market model, which focuses on meeting customer needs, creating scientific partnerships, providing best-in-class primary care and patient education to help HCPs deliver great outcomes for their patients. Now, let me tell you a little bit more about the Pfizer Internal Medicine business unit, where this new franchise will sit. Anchored by the market-leading anticoagulant, Eliquis, and with a significant presence in women's health, Internal Medicine is the home of multiple customer-facing teams in commercial and medical who engage with integrated delivery networks, hospitals, ambulatory centers, primary care physicians, and OBGYNs. Nurtec ODT and zavegepant, when approved, will fit well into this portfolio and bring another market leader for Pfizer in Internal Medicine. In addition to the marketed products, IM has a deep pipeline with potentially best-in-class or first-in-class breakthrough assets in diabetes, obesity, NASH, and heart failure, among others.
Now let me double-click on the market opportunity. Migraine treatment and prevention represents attractive incremental growth potential. First, migraine is extremely common, with 1 billion people, or over 11% of the population worldwide suffering from migraine. In the U.S. alone, this amounts to 40 million people, which is one in five women. Migraine is also debilitating. When at its most severe, it is categorized by the World Health Organization as among the most disabling illnesses in the world. Its impact is also magnified. Migraines are very prevalent among younger, working-age people who care for their families. At the same time, the unmet medical need is acute. Current standards of care aren't effective, convenient, or tolerable for many patients. However, not only does migraine put a high burden on sufferers and their families, it also impacts the economy.
Migraines cost the U.S. economy 157 million workdays and $36 billion per year. Nurtec ODT will help address these needs. It offers an effective oral treatment that can be conveniently used for both episodic prevention and treatment for those who suffer with migraines, and we expect to see robust growth ahead for the class as well. I'm sure you saw that Vydura was recently approved in Europe, and we couldn't be more thrilled about the opportunity to now bring this medicine to patients suffering across Europe. In addition, the product is approved in other markets, including the UAE, Israel, and the U.S. We look forward to building on this momentum in other markets this year, including the U.K. and China.
Zavegepant is Biohaven's next oral CGRP asset, which they expect filing acceptance for the intranasal formulation later this quarter, following the previously announced positive phase 3 results. The intranasal form has ultra-fast activity, with improvements seen versus placebo in as few as 15 minutes and allows use in people with migraine who endure symptoms of nausea and vomiting, and they represent 40% of sufferers. Biohaven also has an oral form of zavegepant in phase 3 clinical trials for prevention, with the results expected in 2023. Now let me turn it over to Vlad to talk about Nurtec's recent performance, including the first quarter financial results that they announced this morning and their expectations for the year. Over to you, Vlad.
Thank you, Angela, for that kind introduction. Today, we took a giant leap forward in delivering on Biohaven's mission to improve the lives of people with neurological diseases. We are excited that Pfizer recognized the value of our migraine franchise and will be delivering this important breakthrough medication to patients. Under the leadership of Pfizer, Nurtec ODT will be well-positioned to continue to thrive, ensuring even greater access to a life-changing migraine medication that finally brings a debilitating disease under control. As a global drug development powerhouse, Pfizer will unlock the full potential of our CGRP franchise, building upon the work we have done the last five years, including advancing Zavegepant, the only intranasal CGRP antagonist for ultra-rapid pain relief in the acute treatment of migraine.
On this momentous occasion, we are hopeful that patients, caretakers, physicians, shareholders, and all key stakeholders of both Pfizer and Biohaven can appreciate the long-term value proposition we are presenting here today. I want to take a few minutes to talk specifically about the continued success of the Nurtec ODT launch and Biohaven's first quarter performance. As Angela mentioned a few minutes ago, we were very proud to announce in the first quarter the European Commission approved rimegepant for both acute and preventative treatment of migraine. With this approval, rimegepant, under the EU trade name Vydura, is now the first approved oral CGRP receptor antagonist in the EU and the only migraine medication approved for both acute and preventative treatment. The Biohaven and Pfizer teams worked together with the regulatory agency in Europe to jointly achieve this incredibly exceptional outcome with an earlier-than-expected approval.
I also want to highlight the continued commercial success of Nurtec ODT with the achievement of approximately 2 million prescriptions written to date in the U.S., an astounding milestone reached only 2 years after our initial launch. Nurtec ODT is the number one prescribed oral CGRP antagonist, and we expect this leadership position will continue going forward. I am also thrilled to report that Nurtec has now achieved best-in-class commercial insurance coverage within the oral CGRP category. Now we have greater than 96% commercial coverage and over 263 million lives covered, which compares to 89% or 238 million lives covered in the fourth quarter.
In addition to the commercial success of Nurtec ODT, our team continues to demonstrate its leadership in advancing the science of pain treatment with 13 presentations at AAN last month. Particularly noteworthy was a podium presentation we made related to a reduction in opiate use in patients after starting Nurtec ODT for their migraine management. Among over 14,000 patients with migraine who used opiates prior to initiating treatment with Nurtec ODT, approximately 41% had no opiate refills in the nine months following initiation. These findings support the benefit of Nurtec ODT as an effective and safe migraine treatment that can reduce the need for opiates, and obviously have very broad and significant long-term implications given the urgency of the opiate crisis. Now turning to Nurtec ODT revenue performance.
Our commercial organization performed strongly, delivering growth volume of TRXs for Nurtec ODT despite the expected first quarter seasonality that we discussed at our last earnings call. Nurtec ODT delivered first quarter net revenue of approximately $124 million, representing a 182% increase over first quarter of 2021 revenue. Although first quarter 2022 represents a decrease in net revenue compared to the fourth quarter of 2021, we did see an increase of 8% in prescription volume compared to last quarter, and the net revenue decrease was anticipated due to the typical first quarter insurance dynamics. Growing Nurtec ODT volume and access for patients requires significant investment.
In these important initial years of product launch, our strategy has been to drive brand trial and adoption of Nurtec ODT by investing in patient support programs and working with payers to ensure patient access, which also results in payer rebates and volume discounts related to the investments we made for incremental access. Of course, this growth was driven in large part by strong TRX volumes as well as the higher wholesale acquisition costs or WAC we receive on our two-packs or 16-tablet count prescriptions, which post our expanded prevention approval in May 2021 has grown relative to total prescriptions. Just to level set for the balance of my discussion, our product offering consists of one-packs of eight tablets and two-packs consisting of 16 tablets, which helps patients flexibly address migraine needs without ever needing to worry about running out of supply.
As expected, resetting of insurance policies and deductibles in the first quarter resulted in an increased copay assistance program costs that are seasonal but do impact first-quarter revenues. Copay assistance was also impacted by the dynamic of the increasing two-pack mix since our approval of prevention last year. We experienced increased volumes in our two-pack sales coupled with an increased cost to support the prescriptions as our average WAC increased. This dynamic sets a high watermark for the year on copay assistance support in January, and we have already seen a steady decline in copay assistance coupled with an increase in the TRX volumes on the latter side of the first quarter, which continues to improve. This is a very positive sign for net revenue growth over the remainder of this year.
With respect to the pack mix, we expect the two packs as a percentage of total sales will continue to grow at a modest rate on a sequential basis as the year progresses. We are estimating approximately 60% of full-year revenues will be achieved in the second half of 2022, slightly lower than the 70% we experienced last year as we benefited from a partial prevention approval, which enhanced our second-half 2021 net revenue growth. We are expecting a substantial rebound in second quarter, driven not only by the alleviation of some of the seasonality factors we touched upon, but also more favorable volume growth. As we have indicated since our post-prevention approval, our one-pack and two-pack offerings represent flexible approaches for migraine sufferers across the spectrum, and their utilization is not necessarily correlated to the intensity or frequency of attacks.
This favorable evolving pack mix and the CGRP oral class growth in the market provide further potential upside. Recall we received the expanded approval for Nurtec in the prevention in May 2021. Since that time, two-packs were increasingly accounting for a greater percentage of volume growth, which has a net favorable impact on our realized revenue per prescription. two-pack product sales are now trending at between 25%-30% of total product sales, and we expect that trend to grow in both acute and prevention as patients demand more freedom to take their medication of choice without fear of supply shortage.
We take a much more constructive outlook for the balance of 2022, seeing favorable overall volume tailwinds as awareness for oral CGRPs has driven patient demand, refining and growing our physician-facing programs, which drove prescription volume and result in a more fulsome payer coverage of 96% that will contribute to less patient friction and access, greater access to Nurtec. To provide additional information on the pacing of the seasonality factors with copay assistance and patient affordability programs, I want to focus on the next slide. Both patient affordability and copay programs reached a high point in January and have already started to decline in February and more appreciably in March, as you can see in the graph on the left. We expect the GTNs related to affordability and seasonality will continue to trend lower over the course of the year.
This will favorably impact our realized revenue per prescription as the year unfolds. In a similar vein, the chart on the right shows the sharp rise in blended copay cost per c-claim paid by Biohaven at the start of the year. That has recently steadily declined, and you can see in April the blended cost has even declined to lower levels than what we observed in December of 2021. In sum, investing in our affordability programs contributed to strong year-end performance, and we're very encouraged that we're observing early down trends in patient affordability utilization and copay cost to Biohaven, which we expect will decrease year-over-year. We think this bodes exceptionally well for the remainder of the year, and we expect to see substantial increases in net revenue from second quarter onward.
Nurtec ODT continues to be the number one migraine treatment in its class, leading in total Rx volume and share. Specifically, looking at week-over-week performance, Nurtec ODT is currently maintaining approximately 48% market share as of the latest script counts. We believe our market leadership position is a byproduct of Nurtec's unique product offering. One dose, no titration, one pill to treat your migraine attacks and prevent future ones from occurring. Nurtec ODT is the only all-in-one migraine therapy, and this will continue to differentiate Nurtec ODT from other classes, assets in the class. We continue to share this next slide every quarter, which shows a visible step forward for the CGRP oral class this period as well. We believe oral CGRP antagonists can ultimately be the first-line therapy for migraine and could account for about 40% of the overall migraine market.
The CGRP oral medications, though still somewhat newer entrants in a deeply entrenched space, continue to make steady inroads in disrupting the broader migraine market in the U.S. You can see the oral CGRP lines are nearly intersecting with the CGRP mAbs this period, and we believe it's only a matter of time before the oral class fully overtakes the mAbs, thanks to the ease of use and patient preference for orals over injectables. Further, the oral CGRP class continues to make steady progress in disrupting triptans and topiramate, which have slowly declined since the emergence of the CGRP class as a whole. Let me provide a little more insight into this specific segment. The oral CGRPs are just at the beginning of our growth trajectory, and Nurtec ODT is changing the standard of care for migraine therapy.
This slide shows the market penetration of the oral CGRPs versus the current standard of care triptans for acute treatment and topiramate for prevention. The oral CGRPs continue to grow market share versus these older therapies, which are associated with cardiovascular risk, cognitive effects, and other adverse events and limited efficacy profiles, as well as the numerous advantages that are now offered by the new oral CGRP class. Since their emergence into the class, the oral CGRPs have shown quarterly increases in both TRX and NBRX volume compared to triptans and topiramate. As you can see, the growth opportunity remains sizable, and we continue to see increased penetration of oral CGRPs as patients become more informed about the fast and lasting benefits of all-in-one Nurtec ODT. Today, only 22% of Nurtec ODT scripts are coming from primary care physicians.
Clearly a segment where Pfizer excels and a massive opportunity ahead. I'll let Nick and team cover this in detail shortly. Pfizer takes over Nurtec ODT at a very important time in its early development in order to shape patient care and deliver this breakthrough medication to patients. Before I turn the call back over to Nick, I want to quickly thank the patients who have enrolled in our clinical trials, their family members and investigators who have participated and are advancing our pipeline. I want to reassure you the mission to improve the migraine standard of care will continue. I also want to thank our visionary investors who have helped fund our studies and our dedicated employees who helped to bring Nurtec ODT to patients.
I'm confident that our mission to restate the standard of care in the migraine therapy and benefit patients will only accelerate under Pfizer's leadership. Thank you to the team at Pfizer for recognizing the importance of this medication, and we're happy to hand it off into your capable hands.
Thank you, Vlad, for your excellent explanation of Biohaven's success with Nurtec and some of the recent dynamics that you have faced. Biohaven is a company we know well. We've tracked its portfolio for several years now, and we're excited to enter into a collaboration with them outside the U.S. in November 2021, buying a stake in the company at $173 per share. Now, we're pleased to own the rest of the company's migraine franchise on the current terms. We've reviewed the Q1 gross-to-net situation as part of our extensive due diligence process, and we understand the dynamics, which is why we've baked it into our forecast already. This is not uncommon, especially during the first few years of a product's life cycle.
What we are compelled by is the long-term potential of Nurtec, the significant unmet need for migraine patients who are limited by the drawbacks of existing migraine therapies. Now, let me walk you through how Pfizer will add value to the migraine portfolio. We have the scale and expertise to further accelerate this best-in-class asset. Upon close, we will double the number of representatives detailing Nurtec and leverage their strengths in primary care, an area, as you've heard just Vlad say, an area that is still under-penetrated for Nurtec. We expect this will allow us to call on an additional 70,000 primary care physicians and OBGYNs. Our US primary care sales force is ranked number one with primary care practitioners and consists of highly experienced representatives with an average tenure of 10 years. Our key account management capabilities are also best in class.
We also expect to significantly expand the non-promotional field-based medical teams by eightfold. They will be laser-focused on peer-to-peer engagement and building healthcare professional confidence. Finally, our real-world evidence team will focus on understanding the impact of migraine on health systems around the world and evaluating real-world utilization of Nurtec and Vydura. The global footprint we will have will allow us to generate real-world data globally, enabling us to further strengthen the scientific platform behind these products and improve the way health systems deliver care for migraine patients and improve patient outcomes. The market for oral CGRPs is very under-penetrated, and we will work to accelerate that. In 2021, they represented only 5% of oral migraine scripts written.
Given their advantages over older drugs on the market, we believe, as we continue to educate doctors and patients about Nurtec, that this class has the ability to grow significantly to more than 40% of scripts, increasing the penetration by eight times. Now let me turn it over to Amir to talk about the fit with Pfizer's business development strategy and to close out our presentation.
Thanks so much, Angela. This transaction aligns with the priorities that Pfizer has previously detailed for our business development efforts. First and foremost, we wanna create value for our shareholders by focusing on breakthrough medicines where we can make a difference. We believe this transaction does exactly that by bringing a breakthrough migraine franchise into our portfolio, which we can then enhance and bring to even more patients with our commercial capabilities, as Angela just articulated. Second, we're looking for bolt-on deals that fit nicely with our existing therapeutic areas and which have the ability to provide meaningful revenue growth in the second half of this decade. The growth trajectory that we expect from Nurtec, Vydura, and Zavegepant delivers squarely during this timeframe. Third, we want to bring in exciting science to strengthen our therapeutic areas, not deals where the primary value driver is cost synergies.
This proposed acquisition brings to Pfizer the leading asset in a high unmet need area, and one where we plan to thoughtfully invest to drive top line growth. Collectively, we believe that the efforts here could enable us to potentially grow these oral CGRPs to more than $6 billion global migraine franchise at peak. Importantly, we've communicated our ambition to add at least $25 billion in risk-adjusted revenues to 2023 through business development transactions. This transaction is expected to contribute significantly to that goal, building on our recent acquisition announcement of ReViral and our recently completed acquisition of Arena. The capital we have planned to deploy at just over 2x peak sales, peak revenues reinforces our belief that we have both the capital necessary and the substrate available to achieve our goal.
In conclusion, migraine is one of the most prevalent diseases worldwide, impacting close to 1 billion patients. There is significant unmet need, severely impacting patients' daily function and ability and overall quality of life. Nurtec is currently the number one prescribed oral CGRP. Experience, scale, capabilities will enable Pfizer to maximize this migraine franchise. With today's announcements, we are maximizing the opportunity for patients, and we expect to create a compelling value for Pfizer shareholders. With that, let me turn it back to Chris for the Q&A.
Thanks, Aamir. We will now be pleased to address your questions. As mentioned earlier, in addition to our speakers, Nick Lagunowich, President of Internal Medicine, Jim Rusnak, IM Chief Development Officer, and Bill Sessa, IM CSO, will also be joining us for the Q&A session. Jesse, please poll for the first question.
Thank you, presenters. Participants, we will now begin the question and answer session. To ask a question over the phone, you may press the star key followed by the number one. To withdraw your request, you may press the pound key. Again, that's star one to ask a question over the phone or the pound key to withdraw your request. Speakers, our first question is from the line of Evan Seigerman of BMO Capital Markets. Your line is now open.
Hi, guys. Thank you so much for taking my question. Really congrats on the deal, and Vlad, it's really good to hear from you. Can you speak to why Pfizer opted not to fully acquire Biohaven's assets? I know that there are some earlier assets, and these arguably could add some interesting science, for what may not have been a significant additional premium to what you paid. Love for you to walk me through kind of the thinking there. Thank you.
Thanks, Evan. Aamir will take that question.
Thanks for that question, Evan. Our business development criteria has been very clear. We wanna focus on breakthroughs that can make a difference for patients, and we wanna focus on where we can add value through our capabilities. In doing that, be very thoughtful and disciplined about how we create value for our shareholders. For us, when we looked at this opportunity, the place where we feel like we can add the most value is on the CGRP franchise through the deployment of our commercial capabilities globally, as Angela articulated, and also in supporting the advancement of zavegepant.
We think that the Biohaven team is very well positioned to advance their other therapies, and this allowed for us to create a creative deal structure that creates value for both sets of shareholders and allows us to continue to be thoughtful and disciplined.
Thanks, Evan. Next question, please.
Your second question is from the line of Louise Chen from Cantor. Your line is now open.
Hi, congratulations on the deal, and thanks for taking my questions here. First question for you is, would you have any interest to add any additional migraine products to your portfolio, such as an injectable toxin or anything like that? Secondly, how do you see the entry of Pfizer into the migraine market potentially disrupting the competitive landscape? Thank you.
Thanks, Louise. Angela, take that question.
Sure. You know, we look at all of our opportunities. I think the principles and the parameters behind our BD deals you heard Aamir talk about. We will continue to look at all opportunities in that vein and when the right one you know emerges, you know, we'll be able to you know take that on. I think the principles behind how we think about BD, how they add value to our you know long-term growth, those are the most you know important parameters to consider, not only just the therapeutic area.
Very good. Thank you. Next question, please.
Your third question is from the line of Robyn Karnauskas of Truist Securities. Your line is now open.
Hi, guys, and congrats on the deal, and thanks again for taking my question. Could you talk a little bit about maybe the rate-limiting steps toward taking more share from the injectables, and why they've held on to the share that they've had, and how you overcome that? Second, what your thoughts for the opportunity for the inhaled version of the intranasal zavegepant. Thanks.
Yeah, that's for Vlad.
Okay. I'm happy to take that. Look at the injectable was launched a couple years ago, and what you've seen is that the oral CGRPs really have taken over the growth in this segment. What you've seen is a plateauing of the injectable monoclonal antibodies. We expect that plateauing is likely to actually start declining. You know, I have to say as a physician, it's a simple choice for patients and patients often will prefer orals over injectables. I think we're gonna continue to do well in the differentiation there, and it is good for patients to have multiple different options. Ultimately, we think this is gonna be a space primarily driven by oral CGRP antagonists.
Thank you. Next question, please.
Your next question is from the line of Terence Flynn of Morgan Stanley. Your line is now open.
Hi. Thanks for taking the questions. Maybe two for me. Aamir, it sounds like based on your comments, you expect to continue along this string-of-pearls strategy, so things like Array, Arena, Biohaven. Just wondering if larger deals are also on the table still at this point. Then, with respect to the commercial opportunity, the peak sales guidance of $6 billion is somewhat ahead of consensus expectations. Just wondering how you guys thought about pricing dynamics, compliance, maybe the ex-US market opportunity, anything you think the Street is underappreciating. Thank you.
Okay. Why don't we have Nick take that question, and then if Amir has anything to add.
Maybe I'll start with the second question first, Chris, and then I'll have Aamir jump back to the question about string of pearls, if that's okay. Okay. You know, the $6 billion, so thank you for the question, Terence. Appreciate it. You know, this market in migraine is incredibly large. Impacts over 1 billion patients globally, and in the U.S. alone, we've got 40 million sufferers of migraine, with only about 20% taking a prescription. This is still underdiagnosed and undertreated. The oral CGRP class has reached blockbuster status already in the U.S. in 2021 with sales of approximately $1 billion combined. Well, it really only accounted at that time in 2021 for 5%-6% of the overall migraine market.
The oral CGRP class, it has the potential to redefine the standard for the reasons that you heard from Vlad, and that we're seeing in the marketplace. We anticipate it's gonna grow to 40% of the total migraine market or potentially beyond. That's 7-8 times higher than in 2021. It, you know, Nurtec ODT, it has that unique market position to both treat, prevent. Its flexibility, I think, is what's so appealing to healthcare professionals and to patients. When you then layer on the zavegepant, the intranasal spray, it relieves pain in less than 15 minutes, and if approved, it'll be a breakthrough for patients who suffer from severe migraines. These are for patients, you know, who have attacks that hit them at the most unpredictable times.
I guess additionally, it's also being developed in an oral form, which adds another option and expands the franchise into chronic migraine as well, potentially. With the addition of the zavegepant to the Nurtec combo, we have potentially the ability to help more patients addressing their needs and bring these innovative treatments forward. Really, you know, in terms of our ability to execute, I think you heard a stat there that 22% of the Nurtec volume's coming in primary care. If you look at sumatriptan, for example, about 50% or so comes from. You can see the gap and the opportunity and the ability to execute in primary care. You heard some stats from Angela in her presentation that talked about the expansion that we're planning.
We plan to double our sales footprint, which will allow us to cover even more PCPs, ambulatory care centers, urgent cares, ED departments, places where these patients seek care. We're gonna add in the U.S. coverage of about 70,000 more PCPs, OBGYNs, and other specialists. We're gonna engage our key account management teams to take an organized system approach. You know, so if you look at the work with primary care as kind of a bottoms-up connection with healthcare professionals, the work that the key account management team is more of a top-down, working with systems of care to identify challenges, understanding the migraine category, and working with those systems to help reduce costs and improve patient care.
Of course, as Angela said, we're gonna build on the body of evidence with our real-world evidence team, which becomes easier, underneath one umbrella, as one company. We're gonna deploy our medical teams to support decision-making, and to make sure that healthcare professionals have the information that they need, to help solve patients' medical challenges. We believe that, you know, this is a growth market. We're incredibly excited about this, and I appreciate the chance to take your question. Thank you.
Terence, on your question on deal size, I think you've seen from our recent deals that we have thoughtfully and deliberately pursued a strategy of diversification between transactions like ReViral, Arena, Trillium, and others. We've been active in multiple therapeutic areas in multiple stages of development, including early commercial with our Biohaven deals. You've also seen us do a combination of acquisitions, but also other forms of collaboration and partnership. We think that that will continue to serve us well. Now, specifically, we've also said we are agnostic to size. If the right larger opportunity presents itself, we certainly have the capital and the capabilities to pursue it. We've also been clear that we're gonna focus on driving our top-line growth in the back half of the decade rather than large deals that are anchored on cost synergies.
Under that lens, we will continue to look at all opportunities, and we're genuinely very excited about the substrate that is ahead.
Thanks, Amir. Thanks, Nick. Next question, please.
Next question is from the line of Charles Duncan with Cantor Fitzgerald. Your line is now open.
Yes, good morning. Thank you for taking my questions, and congratulations to both teams on the transformational transaction for patients and other stakeholders. I had a question regarding the Nurtec-driven migraine franchise, and specifically, when you think about zavegepant, the drug that may be approved, how could that really add to the current very successful Nurtec franchise? I had a follow-up regarding the royalties, sub-royalties to Biohaven. Can you provide any color on how you anticipate those being paid?
Vlad will talk about the first part on zavegepant, and then Dave will talk about the royalties, Charles.
Charles, thanks for the question. You know, we really think that zavegepant is gonna be a nice complementary medication for patients suffering from migraine. As I said earlier, we know patients typically prefer orals over other routes of administration. Typically, it's orals are preferred over intranasal, over injectables. Intranasal becomes very important for the speed of onset because you don't know when a migraine is going to hit. As Nick commented, we have a very quick speed of onset for intranasal zavegepant within 15 minutes. If a migraine is striking as you're trying to get out of the house or an important you know, business meeting or the like, you'll have a nice option there. In many ways, with Biohaven, we've thought of it as the EpiPen of migraine, right?
Everyone with migraine should have a zavegepant intranasal around to take control of their migraine, and make sure it doesn't get in their way if it comes up in a most inopportune time. Lastly, I would add about half the patients experience some nausea or vomiting during a migraine attack. What's interesting is the degree of nausea, vomiting does vary between attacks, and sometimes you can't take an oral pill. Again, the intranasal zavegepant offers that flexibility to patients. We think it's gonna be a nice complementary addition to the franchise.
Charles, this is Dave. I think specifically as it relates to your question, one, I'll just point you to a review of the 8-K that Biohaven will be filing later today after the market closes with the SEC on specific deal terms. Specifically to your point around royalties, suffice it to say, think about this as a low double-digit % for U.S. sales at each tier of sales above $5.25 billion on an annual basis.
Great. Thank you very much. Next question, please.
Your next question is from the line of Mohit Bansal of Wells Fargo. Your line's now open.
Great. Thanks for taking my question and congrats on the deal. Maybe, if you can talk a little bit about the process of deciding the capitalization of the new company. Given that they have multiple phase three or phase two-ready assets, how do you determine the capitalization? Could this be an FTC issue in terms of whether or not the new company is getting enough money? Thank you.
That's a question for Vlad, please.
Yeah, I'm happy to take that. We spent some time ensuring that the new company would be adequately capitalized, and, you know, the amount going into that company will be sufficient to get us through our inflection points in well over a year. I know typically we like to only guide, you know, just over a year, but it's actually a longer period than that. I would also point out that we do have some important trial readouts coming up very shortly on some of those programs, and that also will affect the company moving forward. We're excited about the new Biohaven, and it's very well capitalized for, you know, our budgetary needs well past a year.
Thank you, Vlad. Next question, please.
Your next question is from the line of Umer Raffat of Evercore. Your line's now open.
Hi, guys. Thanks for taking my question. I wanna start by saying a huge congratulations to Vlad and his team for all the hard work over the years. Maybe Vlad, let me ask you a question on the call first. Can you remind us how many total patients have taken the drug so far on a cumulative basis commercially, and what are you learning about the average duration and prevention setting? I had a couple for the Pfizer team as well. Could you walk us through? I understand you're implying $5 billion sales potential, but what's the break even net of Bristol payments, Royalty Pharma payments, and the debt, et cetera. What's that break even to make this deal at least be break even? Secondly, what are your expectations on the 724 patent?
Okay.
As in, are you expecting to go out to '724 patent?
First question's for Vlad.
on the first question.
Can you give the number of patients?
The number of patients, sorry, Umer, thanks for the question, by the way. How are you? To date, we have over 2 million prescriptions of Nurtec. We haven't kind of characterized it as the exact number of patients, but we're at the very early stages in the hundreds of thousands, several hundreds of thousands of patients. We do know that is increasing quarter-over-quarter. We're really excited about the growth. As trial continues, we see further adoption by both physicians and patients. The duration of use, Umer, is interesting. Since the prevention indication, we are seeing an increase of pill utilization and number of second APICs. That has brought our total number of pills up.
Patients we hear really appreciate the ability to flex back and forth between acute and prevention. Not only does that help with the pill count and the durability of refills, but it gives patients real maximum control over their migraine in order to, you know, dial up or down prevention as they need it in their lives. Thanks.
Hey, Umer, this is Dave. I think just a couple things to keep in mind. One, as Angela said, this is a market where we have 1 billion patients worldwide that really has an unmet need from a therapeutic perspective, number one. Secondly, our forecast is for peak volumes of around $6 billion. I would say that as we look at the deal structure and we look at the economics around the deal, not only is this deal gonna drive significant value for the patients that we're gonna serve globally, but importantly, it's gonna have a high level return for Pfizer shareholders specifically.
Thanks very much. Next question, please.
Your next question is from the line of Chris Shibutani of Goldman Sachs. Your line is now open.
Hi, this is Dan on for Chris. Thanks for taking our question, and congrats on the deal. Two from us. First, could you please talk about your focus on partnerships within your business development strategy? Are there certain areas or situations where you see this as most advantageous, and do you see it as a potential precursor to full acquisitions as it was in this situation? Second, on the ex-U.S. opportunity within the $6 billion peak sales, if you could talk generally just kind of about the contribution ex-U.S. to your expectations of the product sales at peak. Thank you.
Okay. Thanks very much, Dan. On partnerships versus full acquisition, Aamir will address that. On the ex-U.S. sales contribution, Nick will address that, please.
Thanks for the question, Dan. On partnerships, as I alluded to earlier, you know, as we embark upon our business development strategy, partnerships are very much part of what we're thinking about. In fact, some of our most successful BD deals have come through collaborations and partnerships. We very much see that as part of what we are going to do going forward. With regards to whether that's a precursor to something else or not, we look at every deal and every transaction and collaboration as what we do in the moment being the right opportunity for us to create value for our shareholders. As situations change over time, we continue to reassess, and we will do that with all of our deals.
Nick, on the ex-U.S. sales. Sorry, go ahead.
Yes. Thanks, Dan, for the question. You know, first, I wanna mention how thrilled we are by the approval in the EU for Vydura. We see significant growth potential outside the US. We're actively planning in 70 markets around the world, and we expect to begin in the second half of the year to bring medicines to patients. We're tremendously excited by the opportunity because, you know, migraine has such a high impact there and high unmet needs globally. You know, this is pretty universal across the board. In terms of your question regarding the mix, we expect to see sales more heavily skewed towards the US. Thanks for the question.
Thank you. Next question, please.
Your next question is from the line of Carter Gould of Barclays. Your line's now open.
Great. Good morning and congrats to both teams.
Following up a little bit on the prior question, you know, since you guys just negotiated the OUS collaboration a few months ago, I guess, can you just comment on kind of what was the spark to change the evolution in the relationship? Was it just getting comfortable with the U.S. competitive dynamics, or did the broader market kind of create an opportunity that wasn't there before? As you think about the deal, did Pfizer make any assumption or have any interest, I guess, in the additional indications, whether the pain adjacency or non-migraine indications and how we should think about those? Thank you.
Thanks for the question, Carter. This is Amir. When we initially did the ex-US deal, we were incredibly excited about the breakthrough potential of the Nurtec in Japan. At the time, we felt the best way for us to add value and create value for our shareholders was to leverage our ex-US commercial capabilities to help accelerate the launch and bring it to patients outside the US. Since then, we've got a chance to know the company better, know the asset better, and we felt that there was an additional opportunity for us to leverage our capabilities in the US. For that reason, we expanded what we're doing in terms of what we're announcing today.
It was very much an evolution of how we saw the opportunity and how we saw the ability to create value and add value. We did both things in a way that we felt was very thoughtful and responsible. With regards to other indications, we're excited to see what the upcoming data will show. To be clear, all of the projections that we've talked about today are focused on the CGRP franchise in migraine. As data becomes available and other opportunities present themselves, we'll certainly look at it and assess it.
Thank you. Next question, please.
Your next question is from the line of Steve Scala of Cowen. Your line is now open.
Thank you very much. I apologize for a skeptical question, but Pfizer noted that there were 1 billion migraine sufferers worldwide. I would imagine that there were hundreds of millions, if not 1 billion migraine sufferers in 2002, when it looks like Imitrex peaked at $1 billion, which I think was the most successful migraine drug ever. I know it's often said that triptans were avoided because of tox, but I watched their development, launch, and decline, and don't recall safety being as big an issue at that time as it is being made out to be today. I don't think Imitrex has a black box. I think that there is a reasonable chance that the Biohaven franchise won't fulfill the potential that Pfizer believes.
How did Pfizer become comfortable that it will be different this time than, say, back in 2002? Thank you.
Yeah. I think Vlad could best address the history there.
I'm happy to talk about also the differentiation versus triptans. I'll say as a physician, I prescribe these, and there is a distinct difference, I believe, in the profile of the novel agents that have come on the market versus the older, triptans and other medications. Take a look at the triptan label. You'll see that, you know, one's supposed to administer the first dose in the presence of a physician due to the vasoconstrictive effects on the cardiovascular, system, as well as, the potential impacts in the cerebral vascular, system. Those when you have new options that don't have those side effects, it's clear that I believe those will become the standard of care due to the lack of vasoconstrictive effects and the lack of effects on cerebral vascular.
I would also add that the older class of medications are well known to cause medication overuse headache or rebound headaches. Think about this. You have migraine, and the treatment that you use actually causes more migraines, right? That's what a rebound headache is. That is a phenomenon you do not see with CGRP class of medications. I think when clinicians and patients who experience the treatments view the new profile of the novel agent, there's a distinct advantage over the older agents regarding those characteristics. I believe we are now moving into a new standard of care that is gonna finally treat migraine the way it should be. I've heard patients tell me when they get a treatment for migraine, they want their migraine going away, and they don't want a lot of new problems.
I think the novel agents bring you closer to that patient desire.
Vlad, thank you very much for that perspective. Next question, please.
Your next question is from the line of Chris Schott of J.P. Morgan. Your line is now open.
Great. Thanks very much. Just two questions from me. I'm sure you have a sense in terms of the Pfizer infrastructure. How much does this deal leverage your existing internal medicine infrastructure, maybe specifically existing sales reps? Or is this more about the company that has experience building markets like this, but we should think about this functioning more as a kind of a standalone migraine franchise with incremental OpEx supporting the step-up in the brand as a whole. So I'm just trying to get a sense of the, I guess, incremental cost associated with the increased support you're gonna put behind the brand. Then the second question was on BD priorities. Are there business units that make particular sense at this point for future deals and where there's capacity to add pipeline and commercial assets over others?
I guess it seems like we've seen a deal in internal medicine. Previously we saw one in I&I. Should we think about those as areas that there maybe is going to be a pause in BD as you digest those acquisitions? Is there enough capacity across the organization that we should kind of think of still the whole scope of the Pfizer, you know, range of business units all looking at transactions going forward? Thank you.
Okay. Thanks for the great question. Angela is going to start, and then Aamir will add on the BD priorities.
Yeah.
Chris, you know, earlier in my opening comments, we talked about the fact that Pfizer's scale and the expertise is what we bring to this deal and what we can do to increase the value. From that perspective, certainly, there are going to be incremental things that we can do, right? Now these incremental things already exist. These are not more people we have to hire or more teams we have to set up. We are already in the primary care space, and we'll be able to add a call list of 70,000 more physicians to what Nurtec is currently doing, just using our existing field force. I think that, you know, and let's take another one, you know, the medical expertise that we also talked about.
We'll be able to, you know, multiple-fold, I think 8 times the amount of medical, you know, peer-to-peer interactions that, over and above what is currently done. Again, just using the existing footprint of Pfizer. I think that from a fixed cost perspective, there is not incremental spending, but of course, the ability to make additional calls, the ability to, you know, expand the opportunity to more targets, more accounts. That's sort of what we bring to the table. Again, it comes back to the scale of the machinery that we have and the depth of expertise that we have in primary care.
Chris, on your question about BD priorities, you know, I mentioned earlier our focus is going to be guided by places where we can bring breakthroughs to patients and where we have the ability to add significant value to shape those breakthroughs. The good thing is, across all of our therapeutic areas, across all of our various functions, we feel that we have ample capabilities and capacity to do many transactions, and we also have the capital firepower to pursue those. You should expect to see us following the science and not limiting our BD focus to any one particular therapeutic area.
We're gonna continue to be very disciplined about where we can leverage those capabilities to create real value for our shareholders, but we see opportunities across the board for us to do that internally and externally. We think the substrate is quite compelling across a broad range of therapeutic areas.
Thank you very much. Operator, we have time for one last question, please.
Last question is from the line of Kerry Holford of Berenberg. Your line is now open.
Thank you. Just two quick ones from me, please. You talked about doubling the number of sales reps in the field. I wonder if you would be willing to detail the actual numbers of reps that Biohaven have in place today. Secondly, is the intranasal CGRP designed to be used as monotherapy in the acute setting, or are you also looking perhaps a combination in the chronic setting, perhaps with Nurtec, for patients who have breakthrough symptoms? Thank you.
Thanks very much. Angela is going to answer the question on the reps.
Just a quick response on that. Just for competitive reasons, it's just a level of detail that we are not able to share both on Biohaven side.
For the combo or mono use for Zavegepant.
Oh, yeah.
Vlad's going to address that.
Yeah, no. Look, patients who need preventive therapy do need something for a breakthrough. Obviously if somebody's on Nurtec, they're going to be able to flick back and forth, and then zavegepant's a different molecule. We do believe it'll be complementary and add to the market share rather than take away from anything on Nurtec. I do wanna comment that I think regardless of whether one's on Nurtec, a mAb, a competitor agent that's an oral, the need for an intranasal. There is no other CGRP antagonist intranasal that can deliver this speed of onset with the profile I referred to earlier, you know, regarding the lack of rebound headaches and lack of addiction potential and lack of cardiovascular effects.
We think that intranasal is gonna be another important tool in patients' toolkit to combat migraine. Thank you, Vlad. Thank you, Angela. Thanks for that question, Kerry. All right. That was our last question. I'd like to thank all of our speakers for their time and our listeners for their interest and for joining us on such short notice. Should you have any further questions, please reach out to the IR team and we'll get you answers. Thank you very much. Good day.
This concludes today's conference call. Thank you all for participating. You may now disconnect.