Vertex Pharmaceuticals Inc. (NASDAQ:VRTX) said it will begin two Phase III combination trials of VX-445, tezacaftor and Kalydeco ivacaftor in cystic fibrosis patients. The trials are designed to support the submission of an NDA to FDA and follow Phase II data of the combination which was also announced on Thursday.
In a Phase II trial in CF patients with two copies of the F508del mutation who were already receiving tezacaftor plus Kalydeco, adding treatment with VX-445 improved mean absolute percent predicted forced expiratory volume in 1 second (ppFEV1) by 11 percentage points from baseline to week four.
The first Phase III study will evaluate the triple combo in about 360 CF patients with one copy of the F508del mutation and one minimal function mutation. The second study will enroll about 100 CF patients with two copies of the F508del mutation.
The company told BioCentury the trials "will begin shortly."
Vertex also reported 1Q18 financial results on Thursday. Total CF product net revenues increased 33% over 1Q17 to $638 million in 1Q18, driven in part by the launch of Symdeko tezacaftor/ivacaftor and global sales of Orkambi ivacaftor/lumacaftor. FDA approved Symdeko in February to treat CF patients ages 12 and older who have two copies of the delta F508 mutation or who have at least one CF gene mutation that is responsive to Symdeko (see BioCentury Extra, Feb. 12).
The company reported non-GAAP EPS of $0.76 for the quarter on revenues of $640.8 million, beating the Street's estimates of $0.62 and $617.6 million, respectively. In 1Q17, Vertex reported non-GAAP EPS of $0.41 and revenues of $715 million.
Vertex also reaffirmed that it expects its CF portfolio to generate $2.65-$2.8 billion in revenue for the year.
European authorities have struggled with Orkambi's cost-effectiveness. NHS England and Vertex have been negotiating reimbursement for Orkambi since 2016 when NICE issued final guidance saying the drug was not cost-effective.
In March, members of Parliament called on the U.K. government to resolve an impasse that has stalled reimbursement discussions after NHS England's most recent counteroffer refused to provide additional room in its budget to fund Orkambi. The proposal would add Orkambi and all future Vertex CF drugs to the current budget allotted to cover the cost of Vertex's Kalydeco, essentially proposing that the company provide Orkambi and all future CF drugs for free on the NHS, according to a person familiar with the matter who requested anonymity (see BioCentury Extra, March 19).
The counterproposal from NHS England followed Vertex's initial offer in February to provide a “portfolio approach” for access to its CF drugs that would be similar to its reimbursement agreement with the Republic of Ireland's Health Service Executive, which covers current and future CF drugs (see BioCentury Extra, March 5).
Vertex canceled three planned French Phase III trials to evaluate double- and triple-combinations of candidate in its next-generation CF portfolio following a similar dispute in France (see BioCentury, Feb. 23).
The company did not explicitly address the U.K. or French negotiations on its earnings conference call Thursday. EVP and COO Ian Smith told the call "we're continuing to pursue with every degree of urgency that we can" in regards to reimbursement for Orkambi.
Vertex added $3.66 to $158.81 on Thursday. The company announced earnings after hours and added an additional $3.19 to $162.