Reshma Kewalramani
Chief Executive Officer and President at Vertex Pharmaceuticals
Thanks, Susie. Good evening all, and thank you for joining us on the call today.
After a strong start to the year, we saw continued momentum into the second quarter across all aspects of the company. Our CF business continues to grow and we are reaching more patients than ever. In the second quarter, this expanded reach drove 14% global CF product revenue growth versus the prior year period. And with this first half performance, we are raising our full year 2023 CF product revenue guidance to a revised range of $9.7 billion to $9.8 billion.
As we continue to deliver in CF, we're also investing for future commercial excellence ahead of multiple potential near-term launches: in exa-cel in both severe sickle cell disease and transfusion-dependent beta thalassemia, which we expect will be the first in our next wave of launches; in VX-548 for acute pain, another multibillion-dollar commercial opportunity; and in our vanzacaftor triple combination therapy for cystic fibrosis, which provides the opportunity to further extend our leadership in CF.
In addition to these four disease areas, our mid-stage clinical pipeline continues to develop rapidly and mark progress towards our five launches in five years goal. Recent achievements include: the VX-147 or inaxaplin pivotal trial remains on track to complete the Phase 2B portion of the study by the end of this year; in our type 1 diabetes program, both VX-880, the naked cells, and VX-264, the cells plus device programs are now in the clinic and dosing patients; additionally, we announced a strategic long-term manufacturing agreement with Lonza for a type 1 diabetes cell therapy programs; and finally, an accelerated timeline for the VX-548 Phase 2 study in peripheral neuropathic pain, where we now expect the study to complete by the end of 2023.
In total, we are advancing programs in eight disease areas through mid and late-stage development, six of which are now past the proof-of-concept stage, as detailed on Slide 5. Beyond our clinical pipeline, we're also advancing the next wave of research stage assets, reflecting program source from both internal and external innovation. This includes programs in Duchenne's muscular dystrophy, myotonic dystrophy type 1, the NaV1.7 program for pain, and gentler conditioning agents for use with exa-cel.
In the CF franchise, in R&D and across the business, this quarter Vertex has continued to make meaningful advancements to bring our CFTR portfolio to more patients around the globe and bring additional first-in-class or best-in-class potentially transformative medicines to multiple new disease areas.
With that overview, I will turn to the details of recent R&D progress starting with CF. While TRIKAFTA delivers tremendous benefit for patients, if it's possible to do better, we're committed to being the ones you do so. And that is the goal for our next in-class vanzacaftor triple combination therapy. I am pleased to share we expect to complete all three Phase 3 studies, SKYLINE 102 and SKYLINE 103 in patients ages 12 years and above and the RIDGELINE study in patients ages six to 11 by the end of 2023, and release results from these three studies in early '24.
We have high expectations from the vanzacaftor triple program to lead to further improvements in CFTR function based on the totality of the evidence generated to date. The most direct readout of higher CFTR function is chloride transport in vitro and sweat chloride in patients. In vitro, our human bronchial epithelial cell assays with the vanzacaftor triple showed greater restoration of chloride transport than with TRIKAFTA. And in Phase 2 in patients, the vanzacaftor triple clinical studies should correspondingly lower levels of sweat chloride than in previous studies with TRIKAFTA. We, therefore, believe the vanzacaftor triple has the potential to provide patients with enhanced clinical benefit, the convenience of once-daily dosing, and additionally, the vanza triple carries a substantially lower royalty burden.
Another important program in our CF portfolio is VX-522, our CFTR mRNA therapy in development with our partners at Moderna for the more than 5,000 CF patients who cannot benefit from CFTR modulators. We have enthusiasm for this approach for three key reasons based on what we've achieved to date. First, the delivery of mRNA at high efficiency into HBE cells in vitro. Second, expression of CFTR protein leading to high levels of chloride transport. And third, successful nebulized delivery of mRNA in both small and large animals resulting in expression of CFTR protein in the desired cells. We continue to enroll and dose CF patients in the single-ascending dose or SAD study of VX-522, and we expect to complete the SAD portion and initiate the multiple-ascending dose portion of the study this year.
Turning now to exa-cel, our CRISPR/Cas9-based gene-editing program for sickle cell disease and transfusion-dependent beta thalassemia, which targets the most severe patients and an estimated patient population of approximately 32,000. Exa-cel holds the promise to be a one-time functional cure for these diseases. On the regulatory front, the FDA has accepted our filings and granted priority review in sickle cell disease with the December 8, PDUFA date, along with the standard review in beta thalassemia with the March 30, 2024, PDUFA date. The FDA has indicated an advisory committee will be held and we look forward to the opportunity to discuss the high unmet need, share results from the exa-cel studies, and discuss the transformative potential exa-cel holds for patients.
Outside the US, in the EU and the UK, reviews for our exa-cel filings are also well underway. Our oral presentation at the most recent EHA meeting in June provided new data that were the basis of the EMA and MHRA regulatory filings. Both trials met the primary and key secondary endpoints with follow-up in some patients of more than 36 months.
The exa-cel EHA results continue to demonstrate a transformative, consistent and durable benefit for patients as measured by freedom from severe vaso-occlusive crises for 94% of SED patients and transfusion independence in 89% of TDT patients. The safety profile was generally consistent busulfan conditioning and bone marrow transplantation.
Another significant opportunity for exa-cel is in younger patients, and the pediatric trials in both sickle cell disease and beta thalassemia are underway. We have enrolled more than half the target number of patients in both pediatric studies and have dosed multiple patients. This is an important area of focus given the opportunity to intervene earlier and potentially prevent organ damage and other complications before they ever occur. As the PDUFA dates approach in the US and reviews come to conclusion in the UK and the EU, we look forward to bringing this one time potentially curative therapy to thousands of patients with severe sickle cell disease and transfusion-dependent beta thalassemia.
Turning next to our pain program and VX-548, our novel highly selective NaV1.8 inhibitor that holds the promise of effective pain relief without the side effects or addictive properties of opioids. In acute pain, I am pleased to share that all three Phase 3 studies, two randomized controlled trials and a single-arm safety and efficacy study will complete by the end of this year with results available in late 2023 or early '24. The pace of this Phase 3 program has been rapid, which we see as indicative of the high unmet need and strong interest in an efficacious non-opioid acute pain therapy. We have high confidence in the outlook for these Phase 3 studies given: one, the genetic and pharmacologic validation of the target; two, multiple proof-of-concept trials with the predecessor molecule and with VX-548 itself; and three, the similar methodology design and endpoints of our Phase 3 studies compared to the Phase 2 program.
Closing on acute pain, recall that the Phase 3 program has been designed to support a broad moderate-to-severe acute pain label, which would enable prescribing and usage across multiple care settings, including in hospital or the ambulatory surgical center, post-discharge and in the home.
We are also studying VX-548 in diabetic peripheral neuropathy or DPN, a type of peripheral neuropathic pain that represents yet another significant area of unmet need and another multi-billion dollar market opportunity. We have previously delivered positive proof-of-concept data in peripheral neuropathic pain with the predecessor molecule, VX-150. The current study in DPN with VX-548 is a 12-week Phase 2 dose-ranging proof-of-concept study. I am pleased to share the timelines for this DPN study has accelerated and we have recently completed enrollment. This study will complete by the end of this year, and we expect to share results in late 2023 or early '24.
Moving now to type 1 diabetes, where we're evaluating stem-cell derived, fully differentiated, insulin-producing islet cells for people with type 1 diabetes. Our goal is to develop a functional cure for the millions of people living with type 1 diabetes, including the more than 2.5 million patients in North America and Europe alone.
The VX-880 program is our foundational cell therapy program for T1D, in which we have already demonstrated proof-of-concept. In the VX-880 trial or the naked cell program, patients take standard immunosuppressants to protect the islets from the immune system. We presented updated clinical data on Parts A and B of the study at the recent American Diabetes Association meeting. The presentation at the ADA showed that all six patients treated with VX-880 and grafted islet cells produced endogenous insulin and had improved glycemic control, while reducing or eliminating exogenous insulin use. Importantly, the two patients with at least one-year follow-up saw a complete elimination of severe hypoglycemic events, maintained hemoglobin A1cs below 7% and were insulin-independent. Further, patients who were earlier on their course of therapy were on a similar trajectory as the two patients with long-term follow-up. Based on these results, the VX-880 trial has now advanced to Part C, where patients are treated concurrently at the full target dose. And as part of our global study plan, we've now opened clinical trial sites in Europe in addition to those already opened in the US and Canada
Our second program, VX-264, the cells plus device program encapsulates these same cells which have already demonstrated proof-of-concept in a proprietary immunoprotective device. And hence, there is no requirement for immunosuppressants. I am pleased to share that enrollment in the VX-264 study has initiated and we have already dosed the first patient.
The third program is our hypoimmune program in which we edit the same fully differentiated cells to cloak them from the immune system. This represents another path to obviate the need for immunosuppressants. In March, we expanded our collaboration with CRISPR Therapeutics into type 1 diabetes to use CRISPR/Cas9 to make these edits, and we continue to make progress in this research stage program.
Transitioning now to inaxaplin or VX-147, the first potential medicine to target the underlying cause of APOL1-mediated kidney disease or AMKD, a genetically-defined disease that affects approximately 100,000 patients in the US and Europe alone. Recall, the inaxaplin pivotal program for patients with AMKD is a single adaptive Phase 2/3 study with a pathway to accelerated approval in the US. The Phase 2B dose-ranging portion of the study continues to enroll and dose and remains on track to complete this year. We also continue to work to enhance AMKD disease awareness and genetic testing availability to support diagnosis, including through partnerships with Natera, a leader in genetic testing, and Arkana, a leader in renal pathology services.
To close and update on our alpha-1 antitrypsin deficiency or AATD program, our small molecule approach targets both the lung and liver manifestations of this disease that affects an estimated 100,000 people in North America and Europe. Our program is exploring two hypotheses. First, longer treatment duration with VX-864. And second, a more potent molecule with VX-634. The Phase 2 program for VX-864, a 48-week study in patients with AATD that assesses both liver clearance of Z polymer and functional plasma AAT levels, is ongoing and is anticipated to complete enrollment later this year. VX-634, the next-in-class molecule with multifold greater potency and better drug-like properties is projected to complete its Phase 1 trial by the end of this year. Overall, the AATD program remains on track and we look forward to sharing results in 2024.
With that, I'll turn it over to Stuart to provide a commercial update, including details on our launch preparations for exa-cel.
