Vertex Pharmaceuticals (NASDAQ:VRTX) continues to make significant progress in being able to advance treatment options for patients with Cystic Fibrosis [CF]. It just reported positive results from several late-stage studies, using its next-generation CF triplet vanzacaftor/tezacaftor/deutivacaftor for the treatment of CF patients. It was shown that this triplet was non-inferior to TRIKAFTA in treating CF patients who have at least one F508del mutation or responsive to triple combination CFTR modulators [CFTRm]. Such non-inferiority of the Vanza triplet was observed in the two phase 3 studies, known as SKYLINE-102 and SKYLINE-103. One area of CF that Vanza did achieve superiority on, which moves the bar forward for these patients, was being able to show sweat chloride level improvements for them.
Especially, what was observed when pediatric patients were given this CF triplet. This moves a new triplet closer to being able to at least improve the lives of CF patients. Why investors should be interested in keeping an eye on this company, is because there are several catalysts to look forward to in 2024. The first of which would be that Vertex expects to submit a New Drug Application [NDA] and a Marketing Authorization Application [MAA] of the Vanza triplet for CF in mid-2024, to the FDA and EMA regulatory authorities respectively. A second catalyst, would be the release of the full data set from all three pivotal studies at upcoming medical meetings throughout 2024.
Positive Vanza Triplet Data Moves Bar Forward For Cystic Fibrosis Patients
As I explained above, Vertex Pharmaceuticals achieved positive results from several late-stage studies using its vanza triplet for the treatment of patients with Cystic Fibrosis [CF]. The first two studies to make note of would be SKYLINE-102 and SKYLINE-103, which tested the use of vanzacaftor, tezacaftor and deutivacaftor to treat CF patients ages 12 and older who had at least one F508del mutation or a mutation responsive to CFTR modulators. The primary endpoint deployed in both of these pivotal studies was noninferiority of Vanza triplet compared to TRIKAFTA on the absolute change from baseline in ppFEV1 through 24-weeks. This primary endpoint was met in both of the studies, because the Vanza triplet proved non-inferiority compared to TRIKAFTA. While it was good to see such non-inferiority, this shows that the Vanza triplet at least is on par with TRIKAFTA in the area of achieving improved lung function, this is not what was advanced in terms of moving the bar forward in the Cystic Fibrosis treatment space. How so then? Well, it all has to do with clinical data released showing that the Vanza triplet was able to achieve superiority in terms of another measure function seen in these patients, which is sweat chloride [SwCl] levels. Consider that the threshold for SwCl levels of > 60 mmol/L result with increased problems for CF patients such as lung function, pulmonary exacerbations, poorer quality of life and terrible survival percentages. The ultimate goal for patients to have a stabilized/normal range of SwCl, would be to get levels below 30 mmol/L. This is the difference in SwCl that was achieved in the pooled studies [SKYLINE-102 and SKYLINE-103] of patients who took the Vanza triplet, compared to those who were given TRIKAFTA instead:
- Vanza triplet – 86% of patients across both trials achieved SwCl levels of < 60 mmol/L through 24 weeks, compared to only 77% in the TRIKAFTA group
An improvement of SwCl was also seen with respect to a lower amount threshold as follows:
- Vanza triplet – 31% of patients across both trials achieved SwCl levels < 30 mmol/L through 24 weeks, compared to only 23% in the TRIKAFTA group
As you can see, a lot more patients benefited taking the Vanza triplet when it came to Sweat Chloride, thus my reasoning on why I believe that this moves the bar forward for CF patients. Both of these measurements in SwCl were achieved with statistical significance. An even more profound effect was observed in another pivotal phase 3 study, known as RIDGELINE-105, which recruited CF patients ages 6 to 11 years of age. SwCl here was greatly improved. How so? Well, the fact that 95% of patients and 53% of patients achieved SwCl levels of < 60 mmol/L through 24 weeks and SwCl levels < 30 mmol/L through 24 weeks respectively. This shows that treating CF patients earlier on in life might help with respect to improving disease outcomes in the future. This newly updated data now leads to Vertex being able to file regulatory applications to the FDA and European Medicines Agency [EMA] for the Vanza triplet for these CF patients. With respect to the U.S. filing, the company has already indicated that it would use its Priority Review Voucher [PRV] for this program. Thus, this would allow for a 6-month review time, instead of the standard 10-month review. I believe this is good news for Vertex and for CF patients, as it would expedite this new CF triplet to provide them with the relief that they need.
Financials
According to the 8-K SEC Filing, Vertex Pharmaceuticals had cash, cash equivalents & total marketable securities of $13.7 billion as of December 31, 2023. The thing is that this biotech is already generating revenue through its CF drug franchise. This would include the net product revenues generated from TRIKAFTA, KALYDECO, SYMDEKO and ORKAMBI. Full-year product revenues for 2023 reached $9.87 billion, which was an increase of 11% compared to full-year 2022 product revenues. The biotech should also be able to increase its net product revenues through the selling of CASGEVY, which was approved in the United States for the treatment of patients with sickle cell disease [SCD] and transfusion dependent thalassemia [TDT]. Both of these regulatory approvals in the U.S. could offer patients a possible one-time cure to treat their disease. Another expansion opportunity might present itself if Vertex can get European approval of CASGEVY for both of these indications. Thus far, it had received a positive opinion from the CHMP using this genetic medicine for both of these indications.
Risks To Business
There are several risks that investors should be aware of before investing in Vertex Pharmaceuticals. The first risk to consider would be with respect to the upcoming filings of the Vanza triplet, which is being advanced for the treatment of patients with CF patients who have the F508del mutation or who are responsive to a CFTR modulator. That’s because there is no assurance that one or either of these regulators are going to accept the regulatory applications of Vanza for the treatment of these patient populations. A second risk would then be the review of this triplet CF therapy, in that there is no guarantee that it will be approved by either regulatory authority for marketing. A third risk to consider would be with respect to ongoing sales of its CF drug franchise. Even though it was able to achieve an increase of net product revenues of 11% in 2023 compared to 2022, there is no guarantee that sales will increase beyond these levels.
A fourth risk to consider would be the FDA approval of CASGEVY. For starters, there is no way of knowing whether or not sales expectations will be met for either the treatment of TDT or SCD. Plus, you have to consider that is not assured that the company will be able to receive European Marketing approval for CASGEVY for the treatment of one or both of these patient populations.
The fifth and final risk to consider would be in relation to an expansion opportunity. That is, there is a goal to advance a drug by the name of VX-522 for the treatment of patients with CF in collaboration with Moderna Therapeutics (MRNA). However, it is important to note that this is going to be a nebulized messenger RNA [mRNA] therapy delivered by lipid nanoparticle [LNP] delivery for the 5,000 patients who don’t benefit from any CFTR modulator treatments. This is being explored in an ongoing phase 1/2 multiple-ascending dose [MAD] study for these patients and data from it is expected to be released either late 2024 or early 2025.
Conclusion
Vertex Pharmaceuticals has continued to make advancements in being able to develop therapies to treat patients with Cystic Fibrosis [CF]. This is evidenced by its pipeline of CF drugs such as KALYDECO, ORKAMBI, SYMDEKO and TRIKAFTA. As I have shown above, the new Vanza triplet is able to help a lot more of these patients achieve improved sweat chloride levels, which in turn should help them see an improvement in several key areas such as lung function, symptoms and other functional measures. The bottom line is that the company has set a higher bar for itself past TRIKAFTA. CASGEGY is another drug that it has been able to achieve approval for in the U.S. for TDT and SCD and could also eventually obtain regulatory approval for the European Union as well for both of these indications.
Its CF franchise remains strong, seeing an 11% net product revenue increase in 2023, compared to 2022 with $9.87 billion in sales. It has an opportunity to eventually target approximately 5,000 CF patients who don’t benefit from CFTR modulatory therapies, through a partnership with Moderna. Again, this would be the advancement of VX-522 which is a nebulized mRNA being specifically developed to only target these specific CF patient population. With continued advancement in its CF franchise with Vanza triplet, plus regulatory filings for it expected in mid-2024, I believe that investors could benefit from any potential gains made here.
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