Reshma Kewalramani
Chief Executive Officer and President at Vertex Pharmaceuticals
Thanks, Michael. I'm pleased to discuss our performance and progress in 2021 and to share our vision for where Vertex is headed. 2021 was a very important year for the Company, during which we expanded our leadership position in CF, significantly advanced the mid and late-stage pipeline and further strengthened our financial position. And one, which sets us up for high-value milestones in 2022 and a very bright future for years to come. Our revenue and earnings continue to reflect the significant growth of our global CF franchise. And based on our success in treating more CF patients, we again delivered exceptional financial results, generating nearly $7.6 billion in product revenues, representing 22% growth year-on-year and 27% growth over Q4 2020. Also in 2021, we initiated two global Phase 3 studies with our next-in-class CF regimen VX-121/tezacaftor/VX-561 completed enrollment in the pivotal studies of CTX001, delivered proof-of-concept with VX-147 in a type of APOL1-mediated kidney disease known as FSGS, delivered early but very promising results with VX-880 in type 1 diabetes and advanced VX-548 into two proof-of-concept studies in acute pain, the results of which are expected this quarter. These advancements span small molecule, gene editing and cell therapies and six disease areas including CF.
Fueled by our success in cystic fibrosis, our financial profile and balance sheet have been further strengthened, enabling both continued investment in internal and external innovation and industry-leading operating margins. We provided a detailed overview of Vertex at our webcast two weeks ago at the J.P. Morgan Conference. Tonight, our prepared remarks will recap the high points around our CF franchise and our pipeline and also review our commercial performance and financial expectations for 2022.
Starting with CF. For the 90% of CF patients who can benefit from a CFTR modulator, we see continued significant growth ahead. As we have more than 25,000 patients who could benefit from TRIKAFTA and our other CF medicines, but who are not yet on treatment. Stuart will discuss the opportunity ahead of us and our high confidence that we will reach these patients in his prepared remarks. Approved first in the US in October of 2019, TRIKAFTA set a high bar in terms of both clinical trials and real-world data and has become the standard of care for patients with CF today.
To recap, in late 2021 we shared 96 week data from the extension of the TRIKAFTA pivotal trial where we saw no decline in mean [Phonetic] lung function. This was the first for any CFTR modulator. We now have the first real-world data for TRIKAFTA from the US CF Foundation Registry, across approximately 16,000 patients treated with TRIKAFTA and represented in the registry in 2020, relative to patients eligible for TRIKAFTA in the year prior to approval, will see an 87% reduction in the risk of lung transplant, a 77% reduction in pulmonary exacerbations, and a 74% reduction in the risk of death.
Nonetheless, if it is possible to deliver better clinical outcomes in TRIKAFTA, we are determined to be the ones who do so. And our next-in-class triple combination of VX-121/tezacaftor/561 which holds that potential is already in pivotal development. We expect completion of enrollment in both Phase 3 SKYLINE trial in late 2022 or early 2023. This combination has the potential for greater clinical benefit, more convenient once-daily dosing and a significantly lower royalty obligation. For the last 10% of CF patients who do not make any CFTR protein with our partners at Moderna, we've now demonstrated that we can not only efficiently deliver full-length CFTR mRNA to human bronchial epithelial cells in vitro but also to bronchial epithelial cells in non-human primates. Solving a longstanding delivery challenge and marking a significant step forward in bringing a treatment for the last 10% of CF patients. Based on these results, IND enabling studies for our CFTR mRNA program are now underway. We plan to file the IND this year with clinical trials beginning thereafter.
Beyond CF, we have a pipeline that is broad and deep and delivering and considerably more advanced compared to a year ago. I'll review a few of our clinical stage programs, each of which is a first-in-class or best-in-class program has the potential to serve a large number of patients and represents a multi-billion dollar opportunity. Beginning with CTX001. Our one-time gene-editing treatment with the potential to provide a functional cure for sickle cell disease and beta thalassemia. This is our most advanced program outside of CF and we expect this will be our next commercial launch.
We're wrapping up discussions with regulators to finalize our submission data package for CTX001 including the number of patients and duration of follow-up. This program accelerated significantly last year, based on strong physician and patient interest. We completed enrollment in both Phase 3 studies, both were oversubscribed and to date we've dosed more than 70 patients. We look forward to sharing more clinical data with CTX001 longer-term follow-up and many more patients at a medical forum later this year, on the way to our planned global regulatory filings by year-end 2022.
Moving onto VX-147 and the APOL1-mediated kidney disease program. In renal medicine, one of the most important genetic discoveries of the last decade was the realization that mutations in the APOL1 gene are a key driver of significant kidney disease. VX-147, our small molecule inhibitor specifically targets this APOL1 protein and in so doing targets the underlying cause of APOL1 mediated kidney disease. In the Phase 2 single-arm study of 16 patients with APOL1-mediated FSGS, VX-147 demonstrated unprecedented reductions in proteinuria, a marker of kidney damage and was generally well tolerated. Importantly, the 47.6% mean reduction in proteinuria was on top of standard of care. These Phase 2 results propel the advancement of VX-147 into pivotal development. Our next step is an end of Phase 2 meeting with the FDA and our goal is to initiate pivotal development targeting the broad AMKD population of approximately 100,000 patients, including but not limited to those with APOL1-mediated FSGS later this quarter.
Turning to type 1 diabetes and VX-880. Type 1 diabetes results from autoimmune destruction of pancreatic islet cells and we have known for some time that whole pancreatic cadaveric islet cell transplantation can be curative. The challenge has been quality and quantity of donor tissue. We believe we have overcome this challenge. We are the only company that has shown we can make allogeneic stem cell derived fully differentiated insulin-producing islet cells and make them at industrial scale.
Our goal with our type 1 diabetes program is to develop a functional cure for this disease, including for the more than 2.5 million people living with Type 1 diabetes in the US and Europe. We shared Day 150 results approximately two weeks ago from the first patient treated with VX-880. This patient had severe long-standing type 1 diabetes and prior treatment with VX-880 had difficult to control sugar levels and multiple severe hypoglycemic events with no detectable endogenous insulin as measured by C-peptide. He had a hemoglobin A1c of 8.6% and was taking 34 units of exogenous insulin daily. The results from this first patient treated with half the targeted dose of VX-880 are remarkable, fasting C-peptide a measure of endogenous insulin production is now over 400 picomoles. Hemoglobin A1c is down to 6.7%. And the patient is on minimal exogenous insulin. VX-880 was generally well tolerated and the patient remains free of symptomatic hypoglycemic events, since the period -- for the period.
I mentioned at the J.P. Morgan Conference earlier this month and it bears repeating, why these results are so foundational. Achieving durable results in type 1 diabetes requires two things, high-quality insulin-producing islet cells, we have that. And a method to protect these cells from the immune system. We can address the immune response in several different ways. Today with VX-880 we're combining the stem cell islets with standard immunosuppression in the Phase 1/2 study. We can shield these same stem cell islets with any immunoprotective device. In this approach, the immunosuppressives would not be needed. This approach is an IND enabling studies and we expect to file the IND later this year, with clinical trials beginning thereafter. And in earlier stages we're using gene-editing technology to make so-called hypoimmune pancreatic islets, yet another approach that eliminates the need for immunosuppressives.
The VX-880 Phase 1/2 clinical trial is up and running at multiple sites. The trial continues to enroll and dose patients. We anticipate sharing data from more patients and a longer duration of follow-up this year. I'll conclude the pipeline overview with VX-548, a novel selective inhibitor of NaV1.8, which is in clinical proof-of-concept studies for acute pain. Two proof-of-concept studies in acute pain were initiated in the second half of 2021, one in patients following abdominal plastic surgery and one in patients following bunionectomy. These studies are dose-ranging, placebo-controlled studies and both include an opioid reference arm. The abdominal plastic study is now completed enrollment and dosing, and the bunionectomy study will complete in the coming weeks. We anticipate having results from both studies this quarter and announcing both results together.
With that, I'll turn it over to Stuart.