Stuart A. Arbuckle
Executive Vice President and Chief Operating Officer at Vertex Pharmaceuticals
Thanks, Reshma. With the recent approvals of CASGEVY in sickle cell disease and transfusion dependent thalassemia in multiple countries and the recent positive results in our pivotal trials for VX-548 in acute pain and for the vanzacaftor triple combination in CF, we are well and truly entering a new era of commercial diversification. As Reshma noted, we delivered strong fourth quarter and full year commercial results in CF as we continue to grow the number of eligible patients receiving our CFTR modulators. Fourth quarter U.S. growth was driven by continued strong performance of TRIKAFTA, including in patients ages two to five years old following the approval for these patients in April. Outside the U.S., we saw continued growth from both label expansions and new reimbursement agreements.
In the near term, we will continue to focus on reaching more eligible patients, including younger age groups, which will provide revenue growth and then we expect to drive further growth with the vanzacaftor triple combination. Given the positive Phase 3 data we released today that demonstrates a strong benefit risk profile and the ability to deliver greater restoration of CFTR function than even TRIKAFTA, we believe the vanzacaftor triple combination will be widely welcomed by the CF community, both as a new treatment option for the greater than 6,000 patients who have discontinued one of our current CFTR modulators and as an opportunity for TRIKAFTA patients to achieve even greater levels of CFTR function.
Longer term, we see additional growth from our mRNA program VX-522 that we are developing in partnership with Moderna for the more than 5,000 CF patients with mutations that do not respond to CFTR modulators. In addition, we recently updated our estimate of the number of people living with CF in North America, Europe and Australia to 92,000 from the previous estimate of 88,000. This increase is in large part due to patients living longer as a result of improvements in CF care, including the advent of CFTR modulators. We expect this trend to continue based on the real world evidence we have generated on the clinical benefits of CFTR modulators and this will also drive long-term growth.
Now turning to CASGEVY and our launches in sickle cell disease and beta thalassemia. Enthusiasm from patients, physicians and payers is very high around the globe and we are focused on translating the scientific and medical innovation that CASGEVY represents into transformative patient benefit in the real world. In countries where CASGEVY has been approved, our sales, reimbursement and access teams as well as patient engagement teams have hit the ground running.
Let me provide some insights on the early days of the launch, starting with physicians. There is tremendous interest in CASGEVY and what it can do for their patients and we see the impact of that in the rapid activation of authorized treatment centers. Less than two months post approval, we already have 12 ATCs in the U.S., three in the EU and one in the Kingdom of Saudi Arabia, all ready to receive patients. Reaction from payers has also been very positive. In the U.S. across commercial and government payers, all eligible CASGEVY patients have case by case coverage through single case agreements. We continue to see excellent progress from payers on the development of their formal medical policies and reimbursement pathways.
We have a contract in place with synergy for up to 100 million lives and are actively engaged with other commercial payers to finalize medical policies which would bring the total percentage of covered lives to over 80%. In the government sector, Medicaid state agencies representing over 60% of sickle cell disease lives have established reimbursement pathways for CASGEVY with an additional 25% of Medicaid sickle cell disease lives in states actively progressing their reimbursement methodologies. In addition, we were pleased to have received the January approval in the U.S. for CASGEVY for transfusion dependent thalassemia patients two and a half months early and are working to achieve a similarly fast trajectory for gaining reimbursement and access for these patients.
Last week, there was an important update by the Biden administration on the CMMI cell and gene therapy access demonstration model that was originally announced in February of 2023 and was recently accelerated for implementation from 2026 to 2025. We believe the CMMI CGT access model could be an important additional path to access and we now have greater clarity on the scope and process to be employed in the model. The model is intended to provide a comprehensive strategy to address barriers to equitable access to cell and gene therapies for Medicaid beneficiaries as well as the long standing inequities of care in the sickle cell disease community
Last week's update also confirmed additional federal funding to support access and included a defined scope of manufacturer provided fertility support in the model in recognition that for patients choosing to embark on the treatment journey, the costs of fertility preservation are a barrier to access. In the meantime, we continue to actively engage with state Medicaid agencies to finalize medical policies for CASGEVY even in advance of the CGT access model to ensure patient access without delay. Outside the U.S., we are pleased that the French National Authority for Health has approved our request for the implementation of an Early Access Program or EAP for TDT patients ages 12 to 35 years. We are delighted to have secured a path to access and payment in France ahead of a national reimbursement agreement and are also in an EAP review process for sickle cell disease patients.
In the U.K. CASGEVY will be reviewed by the highly specialized technology committee in February and we are advancing our reimbursement discussions in other European countries as well. We also see strong progress in the Middle East, which is especially important for CASGEVY given the high prevalence of these diseases in the region and the government's clear focus on elevating the health of their citizens. We are working with local healthcare authorities in the Kingdom of Saudi Arabia and Bahrain to refine our estimates of the exact number of eligible patients, but there are thousands of patients we could serve and we are focused on securing access and reimbursement for them.
We have established a local presence in the region, have already activated our first ATC and are working with local healthcare professionals to expand the number of ATCs and establish the required infrastructure to meet patient demand. As we have previously outlined, the CASGEVY patient journey can be broken down into three key phases, each of which can take several months, pretreatment, cell collection and manufacturing and then infusion of the edited cells. We are pleased with the early days of what will be a foundational year for CASGEVY as we work to deliver transformative patient outcomes with the possibility of a lifetime of benefit. We look forward to updating you on the CASGEVY launch over the course of this year.
To help track our progress, our expectation is to provide quarterly updates on the number of activated ATCs as well as the number of patients in the cell collection phase. ATCs have begun assessing their patients for the ability to be treated with CASGEVY and we expect that the first commercial patients will start the journey in the coming weeks.
Shifting now to VX-548. We are very excited about the potential for this highly selective NaV 1.8 inhibitor to provide a transformative treatment option for the millions of patients suffering from acute and peripheral neuropathic pain. This quarter, I'll limit my comments to acute pain. As we discussed last week when we shared the results from the pivotal program, we are very excited about VX-548's compelling combination of efficacy and safety and the demonstration that it can be used for moderate to severe pain across a range of pain conditions, both surgical and nonsurgical and across a range of settings. If approved, VX-548 will be the first of a new class of medicines that inhibit the pain signal and represent the first new class of medicines for acute pain in over 20 years.
The reason we're so excited about the potential for VX-548 to positively impact patient care is because we estimate approximately 80 million patients are prescribed a medicine for moderate to severe acute pain every year in the U.S. representing over 1 billion calendar days of treatment. Given this massive patient population, acute pain is a multibillion dollar market today despite the fact that essentially all prescriptions are generic. We also see upside to this market opportunity given the significant unmet need that stems from the suboptimal benefit risk profiles of existing agents, such as the limited efficacy, but acceptable side effects of NSAIDs or the adverse effects and addiction potential of opioids, all of which leads to suboptimal pain management.
What physicians and patients seek is a medicine that combines effective relief of moderate to severe pain with a clear safety and tolerability profile and VX-548 delivers on that profile. We've previously shared our go-to-market strategy and we are now actively recruiting our field force in anticipation of our regulatory filing and approval. The commercial team will focus on the roughly 2,000 hospitals and institutions where a majority of acute pain patients are seen and prescriptions are written. We continue to see a multibillion dollar opportunity for VX-548 in acute pain alone. The well known risks of opioids have led to widespread restrictions and limitations on their use over the years.
Increasingly, we are seeing a paradigm shift in policy initiatives across various stakeholders to encourage consideration and use of nonopioid alternatives and to remove financial barriers to choosing a branded nonopioid. As an example, late last month, Congress introduced the bipartisan alternatives to prevent addiction in the Nation Act or the Alternatives to Pain Act in. If enacted, Medicare Part D plans would be required to set copays for nonopioids like VX-548 in line with copays for generic opioids, which are typically between $0 and $15. The bill would also prohibit Medicare Part D plans from requiring seniors to step through opioids first or requiring prior authorization for nonopioids.
In addition, the No Pain Act or Nonopioids Prevent Addiction in the Nation Act, which was enacted in late 2022, provides for an add-on payment for nonopioids in the outpatient and ambulatory surgery center settings and remains on track to go into effect in 2025. And just recently, seven states, Maine, Massachusetts, Missouri, Oklahoma, Tennessee, Washington and West Virginia have pending legislation that would require education on nonopioid options and would remove financial barriers to patient access within state based health insurance programs like Medicaid. We expect additional states to introduce similar legislation later this year.
We believe that these advances in federal and state legislation represent further momentum in Congress and across the U.S. to encourage adoption of and remove any financial barriers to using nonopioid therapies like VX-548. In conclusion, it's an incredibly exciting time at Vertex. We continue to treat more CF patients around the world and with the vanza triple now have visibility to provide an option for the patients who have discontinued CFTR modulators as well as the possibility to bring even more patients below diagnostic levels and even to carrier levels of sweat chloride.
We're entering a new era of commercial diversification with the launch of CASGEVY, the first ever gene edited therapy that brings a potential functional cure to patients with sickle cell disease and beta thalassemia across multiple regions and we are preparing for additional near term launches with significant market potential, including VX-548 in acute pain.
I'll now turn the call over to Charlie to review the financials.
