Eli Lilly and Co. (NYSE:LLY) fell $6.70 to $79.44 on Monday, losing more than $7 billion in market cap after it said it will discontinue development of cholesteryl ester transfer protein (CETP) inhibitor evacetrapib (LY2484595) to treat atherosclerotic cardiovascular disease. The company said an independent data monitoring committee recommended terminating the Phase III ACCELERATE trial because there was a "low probability" the study would meet its primary endpoint.
Lilly said safety findings were not a factor in stopping the 12,095-patient study. The placebo-controlled trial evaluated high-risk vascular disease patients for time to first occurrence of cardiovascular death, myocardial infarction, stroke, coronary revascularization or hospitalization for unstable angina. The company said it would present results at an upcoming scientific meeting.
Lilly spokesperson Scott MacGregor told BioCentury that all studies of evacetrapib would be halted, including ACCELERATE, the Phase III ACCENTUATE trial and a "couple other smaller studies." ACCENTUATE measured LDL-C reduction in patients with high cholesterol.
In 2011, Lilly said evacetrapib produced greater increases in HDL-C and reductions in LDL-C than placebo or statin monotherapy in a Phase II trial (see BioCentury Extra, Nov. 15, 2011).
Lilly said it would take a charge to R&D expense of up to $90 million pre-tax, or about $0.05 per share post-tax, in 4Q15. It plans to update its 2015 guidance on Oct. 22.
Merck & Co. Inc. (NYSE:MRK) dipped $0.24 to $50.71 on Monday. It expects results in 2017 from the Phase III REVEAL cardiovascular outcomes trial (CVOT) of its CETP inhibitor, anacetrapib (MK-0859). Merck began the study in 2011.
Amgen Inc. (NASDAQ:AMGN) gained $3.44 to $153.03. Last month, it said it would acquire Dezima Pharma B.V., whose CETP inhibitor TA-8995 has completed Phase IIb testing to treat dyslipidemia. Dezima shareholders received $300 million up front and are eligible for $1.3 billion in milestones plus royalties (see BioCentury, Sept. 21).
Innovent Biologics Inc. (Suzhou, China) and Eli Lilly and Co. (NYSE:LLY) signed their second deal this year, a partnership to co-develop three preclinical immuno-oncology bispecific antibodies. All three target PD-1. The second targets for each of the molecules are undisclosed, though Innovent CEO Michael Yu told BioCentury they are all "checkpoint related."
Lilly is responsible for ex-China development and commercialization, while Innovent is responsible for development and commercialization in China. Lilly has an option to co-develop the bispecific antibodies in China.
Innovent is eligible for more than $1 billion in development, regulatory and sales milestones for the three bispecific molecules, plus royalties. Yu said further financial details are not disclosed, including whether Innovent received an upfront payment.
In March, the companies partnered to develop and commercialize three cancer mAbs, including a biosimilar of Rituxan rituximab from Roche (SIX:ROG; OTCQX:RHHBY). The deal was the first in which a Chinese company out-licensed a Chinese-discovered biologic to a large global pharma, according to Yu. Innovent received $56 million up front; it is eligible for over $400 million in milestones for the Rituxan biosimilar (see BioCentury Extra, March 20).
Yu said the other two compounds under the March deal are a mAb against PD-1 from Innovent and Lilly's merestinib (LY2801653), an inhibitor of the c-Met receptor tyrosine kinase (c-MET; MET; HGFR; c-Met proto-oncogene).
Yu told BioCentury that Innovent is "evaluating all its options in terms of when and where we should go public." He said the company has more than $170 million in cash, including a $100 million series C round closed in January (see BioCentury, Jan. 26).
Vertex Pharmaceuticals Inc. (NASDAQ:VRTX) said it will begin Phase I studies next month of VX-440 and VX-152, two next-generation correctors of cystic fibrosis transmembrane conductance regulator (CFTR). In an investor presentation Friday, CEO Jeffrey Leiden said Vertex hoped that triple combinations including the new candidates could allow the company to treat 80-90% of CF patients.
Vertex presented in vitro data showing that either VX-440 or VX-152 in combination with the company's VX-661 and Kalydeco ivacaftor increased chloride transport and cilia beating compared with Orkambi ivacaftor/lumacaftor in human bronchial epithelial cells with at least one copy of the F508 CFTR mutation.
Leiden said the triple therapy of Kalydeco, small-molecule CFTR corrector VX-661 and either VX-440 or VX-152 could be effective in all CF patients with at least one copy of the F508 mutation, representing about 80-90% of CF patients.
Orkambi combines Kalydeco, a small molecule CFTR potentiator, with lumacaftor (VX-809), a CFTR conformational stabilizer. The therapy is approved to treat CF in patients aged 12 and older homozygous for the F508 mutation.
Last week, Vertex said FDA accepted and granted Priority Review to an sNDA for Kalydeco to treat CF in patients aged two and older with one of 23 residual function mutations. The drug is approved in the U.S. to treat CF in patients with one of 10 CF mutations. Vertex said 1,500 additional patients could be eligible for treatment under the expanded indication. The PDUFA date is Feb. 6, 2016.
Vertex gained $3.25 to $113.25 on Monday. Its investor presentation was held after market close Friday.
Patara Pharma Inc. (San Diego, Calif.) raised $26 million in a series A round and began two Phase II trials of PA101B, an agonist of G protein-coupled receptor 35 (GPR35) that stabilizes mast cells. The company did not name its investors, and did not respond to inquiries.
Patara said it started a European Phase II study of PA101B to treat patients with refractory chronic cough, including those with idiopathic pulmonary fibrosis (IPF). It also started a two-part, European Phase II study of the molecule to treat indolent systemic mastocytosis.
The company also secured a loan of up to $7 million from Silicon Valley Bank.
California Gov. Jerry Brown vetoed the California Right to Try Act (AB-159), which would have allowed drug manufacturers and physicians to provide eligible terminally ill patients with investigational therapies that have completed a Phase I trial but have not been approved by FDA. The California Senate and Assembly passed the bill last month (see BioCentury Extra, Sept. 3).
In his veto message to legislators, Brown said FDA's compassionate use program should be given "a chance to work" before the state authorizes an alternative pathway.
Goldwater Institute Deputy National Policy Advisor Craig Handzlik told BioCentury right-to-try bills were passed in all 24 other states in which they were introduced. The Goldwater Institute drafted model legislation for the state bills last year (see BioCentury, June 30, 2014).
EMA launched an initiative to improve the use of existing clinical registries in regulatory decision-making and to create new registries when necessary.
The agency proposed a strategy in which it would evaluate existing data sources including patient registries, electronic health records and national databases, and develop a methodology to establish new registries as needed. A cross-committee task force on registries, which EMA set up in 2014, will evaluate the initiative following a two-year pilot phase to test the strategy and determine whether it meets regulators' and stakeholders' needs.
FDA granted premarket approval to the PD-L1 IHC 28-8 pharmDx test from the Dako A/S subsidiary of Agilent Technolgies Inc. (NYSE:A), a complementary diagnostic to Opdivo nivolumab. The Oct. 9 BioCentury Extra incorrectly stated the test was approved as a companion diagnostic.
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