Pavan Kottamasu, GlobalData Healthcare & Pharmaceutical Analyst, Jeffrey Leiden, M.D., Ph.D., Chairman, President, and CEO of Vertex Pharmaceuticals, took the stage on Day 1 of the 2018 J.P. Morgan (JPM) Healthcare Conference at the Westin St. Francis in San Francisco, California, US, to present Vertex Pharmaceuticals’ key achieved milestones of 2017 and proposed goals for 2018.

Leiden remarked that Vertex’s strategy will continue to remain the same as it was in 2017 through 2018 and beyond. The strategy consists of three drivers for short and long-term growth, which include achieving Vertex’s vision of providing a curative therapy for all cystic fibrosis (CF) patients, expanding the pipeline beyond CF to other disease indications, and building financial strength in order to continue investment in internal research and development (R&D) and to execute business development strategy.

Leven announced that 2017 had been a pivotal year for Vertex. In May 2017, the FDA approved Kalydeco (ivacaftor), one of Vertex’s approved cystic fibrosis transmembrane conductance regulator (CFTR) modulators, for 23 missense residual function mutations. In August 2017, the FDA approved Kalydeco for five additional splice residual function mutations. Kalydeco’s label expansion increased its eligible patient population from 8% to 13% in the US. More importantly, the FDA announced that it would use in vitro testing to assess rare mutations, thereby allowing for laboratory evaluations of rare CFTR mutations that are not studied in clinical trials and opening a new era of personalized CF medicine.

Vertex’s Phase III EVOLVE study, which investigated the efficacy and safety of the dual combination therapy ivacaftor/tezacaftor, achieved its primary endpoint of absolute forced expiratory volume (FEV1) change (p < 0.0001) in CF patients with two F508del mutations, which is the same patient population eligible for Orkambi (ivacaftor/lumacaftor) treatment. Orkambi is Vertex’s other approved CFTR modulator that has faced problems obtaining reimbursement in many outside the US (OUS) countries. Ivacaftor/tezacaftor’s side-effect profile was found to be similar to placebo, which was of major significance, since Orkambi can occasionally cause chest tightness for 15–20% of CF patients. Fewer drug-drug interactions were observed in patients taking ivacaftor/tezacaftor compared to Orkambi, thus reducing the effects on liver metabolism. As such, ivacaftor/tezacaftor can potentially treat CF patients with two F508del mutations more effectively than Orkambi.

In addition, ivacaftor/tezacaftor was found to have improved absolute FEV1 change by 6.8% (p < 0.0001), while ivacaftor alone was found to have improved FEV1 change by 4.7% (p < 0.0001) in patients with one F508del mutation and a Kalydeco-approved residual function mutation in Vertex’s Phase III EXPAND study. The trial showed that ivacaftor/tezacaftor is likely to be more beneficial than ivacaftor alone in CF patients with one F508del mutation and a Kalydeco-approved residual function mutation.

Leiden added that Vertex expects FDA approval of ivacaftor/tezacaftor in H1 2018, and EU approval in H2 2018.

Vertex also reported positive Phase I and II proof-of-concept data for its multiple triple combination regimens that utilize next-generation correctors along with ivacaftor and tezacaftor in CF patients. According to Leiden, these triple combination regimens have the potential to provide additional benefit for up to 90% of all CF patients. Based on the complete Phase II data for the triple combination therapies, which should be announced during H1 2018, Vertex will choose one or two of the next-generation correctors to move forward to Phase III triple combination development with ivacaftor and tezacaftor.

While finding a curative therapy for all CF patients remains the long term goal for Vertex, it has also invested in expanding its pipeline beyond CF to cover 12 additional disease indications, including sickle cell disease and beta thalassemia, adrenoleukodystrophy, alpha-1 antitrypsin deficiency, and polycystic kidney disease.

Leiden emphasized that Vertex’s development strategy for the new disease indications follows the same four research principles used for CF. Going forward, Vertex plans to focus on creating clinical biomarkers to be able to better predict outcomes.

Rather than develop symptomatic therapies, Vertex will focus on validated underlying disease targets. As such, Leiden expects that the drugs that Vertex pursues will be those that have transformative potential. Vertex will also strive to identify a rapid development path to registration and approval, which will allow patients to receive treatments sooner rather than later.

Leiden concluded his presentation by showing how Vertex expects to build up its assets and optimize product sales in the near future. Key drivers for growth in 2018 and beyond include the planned launch of ivacaftor/tezacaftor in the US, reimbursement for Orkambi in OUS countries, and label expansions of currently marketed therapies to cover additional mutations.

Although Vertex expects to have generated $2.1B to $2.15B in CF revenue for 2017, Leiden did not release the company’s 2018 guidance during the conference. Leiden did, however, highlight that Vertex’s year-end net cash flow is expected to be $2B for 2017, $900M more than 2016.

In 2017, Vertex sealed a partnership with CRISPR Therapeutics to co-develop and co-commercialize a CRISPR/Cas9 gene edited treatment for sickle cell disease and beta thalassemia, and purchased a pipeline CF therapy from CoNCERT Pharmaceuticals. With the company’s increased cash flow, GlobalData expects Vertex to be on the buying end of many deals and to continue bolstering its pipeline with internal and external assets, complementing its ongoing research and development in CF, and accessing promising platform technologies.