Orexigen Therapeutics Inc. (NASDAQ:OREX) gained $1.85 (32%) to $7.64 after an interim analysis of the LIGHT cardiovascular (CV) outcomes study showed that the company's obesity drug Contrave naltrexone/bupropion may have a cardiovascular benefit. The data release could compromise the ongoing trial, but FDA had already requested a second trial when it approved Contrave last fall.
Data from the LIGHT trial appeared in an SEC filing on Tuesday after the U.S. Patent and Trademark Office issued Patent No. 8,969,371, which also included the new CV data. The 8,910-patient trial's primary endpoint measured Contrave's effect on the combined incidence of myocardial infarction, stroke and CV mortality compared to placebo. The interim analysis included 94 major adverse cardiovascular events (MACE), 25% of the planned MACE for the entire study. In the analysis, Contrave reduced the risk of MACE by 41% (95% CI: 0.39, 0.90; p<0.0001) vs. placebo. Rates of myocardial infarction (p<0.0001), stroke (p=0.0088) and CV death (p<0.0001) were all lower in the Contrave group vs. placebo. Contrave is the first obesity drug to show a possible cardiovascular benefit.
Leerink analyst Paul Matteis wrote in a note that the data "could have a positive impact on the Contrave launch if they are included on the drug's U.S. label or ex-U.S. labels." The current label says the effect of Contrave on CV morbidity and mortality has not been established. Contrave is under review in Europe.
FDA requested the LIGHT study as part of a 2011 complete response letter. The agency approved Contrave last September after an interim analysis met a prespecified threshold for cardiovascular safety. However, data from the interim analysis were not disclosed at the time.
In a statement to BioCentury on Tuesday, the agency cautioned that the preliminary data are "far too unreliable to conclude anything further about the cardiovascular safety of Contrave."
Steven Nissen, chairman of the cardiovascular medicine department at the Cleveland Clinic and lead investigator on LIGHT, said that release of the interim data was "strictly forbidden" and was not approved by either the trial's data monitoring committee or its executive committee.
Orexigen said in a statement that it released the data because once the patent and supporting documentation were published, the company "believed it was appropriate and necessary to make sure this information was equally available to all investors." The company said it is committed to meeting its obligations to regulatory authorities including the SEC and EMA, as well as its "fiduciary duties to shareholders."
FDA had voiced concern last year that Orexigen had disclosed or could inadvertently disclose the interim analysis to too many people and potentially bias the ongoing trial. Thus, when the agency approved Contrave in September it required a second cardiovascular outcomes trial (see BioCentury, Sept. 22,2014).
Orexigen expects to begin that trial later this year, and anticipates data by 2022. The company declined to comment on how the early data disclosure would affect enrollment in the new trial.
Takeda Pharmaceutical Co. Ltd. (Tokyo:4502) markets Contrave in the U.S.
In December, EMA's CHMP issued a positive opinion on the drug, which would be marketed as Mysimba in the EU.
Johnson & Johnson (NYSE:JNJ) launched the fourth incubator in its JLABS network, located in South San Francisco, Calif., and named the first 10 companies in residence. J&J said the incubator can accommodate up to 50 startups.
Eight of the 10 are therapeutics companies. One, Applied Molecular Transport LLC, has already granted the pharma's Janssen Biotech Inc. unit exclusive, worldwide rights to a preclinical candidate to treat inflammatory bowel disease (IBD) (see BioCentury Extra, Jan. 28, 2015).
The group includes two gene therapy plays, Goleini Inc. and Audentes Therapeutics Inc., to treat glaucoma and rare diseases, respectively. Audentes, which raised $42.5 million in a series B round in December, is focused on musculoskeletal disorders (see BioCentury, Oct. 13, 2014).
The incubator will also house Driver Bioengineering, which develops remote controlled chimeric antigen receptors (CARs); Ab Initio Biotherapeutics, an immuno-oncology company developing therapeutic proteins that are not antibodies; Afferent Pharmaceuticals Inc., a start-up developing small molecules targeting P2X3 receptors for a variety of indications; and Alkahest Inc. and Cortexyme Inc., both addressing neurodegenerative disorders associated with aging.
The others are MiNDERA Corp., a diagnostics company focused on skin diseases; and EpiBiome Inc., a microbiome company targeting problematic bacteria in agriculture.
JLABS already has incubators in San Francisco, San Diego and Boston. It expects to open a fifth incubator in 2016, within the Innovation Institute at Texas Medical Center in Houston (see BioCentury Extra, Oct. 23, 2014).
The JLABS network now hosts more than 80 companies, which have signed 20 deals with J&J.
The U.K.'s NICE published draft guidance recommending Harvoni ledipasvir/sofosbuvir from Gilead Sciences Inc. (NASDAQ:GILD) as a cost-effective treatment for certain subpopulations of patients with HCV genotypes 1 and 4 at a list price of L38,980 ($60,017) for a 12-week course. Comments are due March 23.
NICE recommended an 8-week course of Harvoni for treatment-naive, non-cirrhotic patients with HCV genotype 1. The committee recommended a 12-week course for treatment-naive genotype 1 and 4 patients with cirrhosis and for previously-treated, non-cirrhotic patients with genotypes 1 or 4. The draft guidance did not recommend Harvoni for previously-treated patients with cirrhosis, nor to treat genotype 3.
The European Commission approved Harvoni last November to treat chronic HCV genotype 1, 3 and 4 infection (see BioCentury Extra, Nov. 18, 2014).
Harvoni's U.K. list price is 36% lower than its $94,500 WAC in the U.S. FDA approved the drug in October (see BioCentury Extra, Oct. 10, 2014).
Harvoni is a once-daily fixed-dose combination of 90 mg of the HCV NS5A protein inhibitor ledipasvir plus 400 mg of Gilead's nucleotide analog HCV NS5B polymerase inhibitor Sovaldi sofosbuvir.
Blueprint Medicines (Cambridge, Mass.) and Alexion Pharmaceuticals Inc. (NASDAQ:ALXN) started a research collaboration to develop small molecules against an undisclosed activated kinase that causes a rare genetic disease.
Alexion will be responsible for clinical development and commercialization of candidates. Blueprint will identify candidates using its platform and will conduct all pre-IND research (see BioCentury, Nov. 10, 2014).
Alexion will pay Blueprint $15 million up front and reimburse its research expenses. Blueprint is eligible for more than $250 million in milestones, plus tiered royalties.
Alexion dipped $2.11 to $182.51 on Tuesday.
Sumitomo Dainippon Pharma Co. Ltd. (Tokyo:4506) named Toru Kimura and Hajime Kinuta executive officers, effective April 1. Kimura is director of Sumitomo's regenerative & cellular medicine office; Kinuta is its director of global corporate planning.
Jon Lorsch, director of the NIH's National Institute of General Medical Sciences (NIGMS), told the U.S. House Appropriations Committee that a new pilot program could make the agency's nearly $2 billion granting process more efficient and introduce a new funding mechanism for early-stage investigators.
NIGMS will begin the Maximizing Investigators' Research Award (MIRA) program in FY16, with $60 million allotted for up to 100 five-year awards. Peter Preusch, program director at NIGMS's division of cell biology and biophysics, told BioCentury he expects the program to begin regardless of budget constraints.
In January, NIGMS said it will first target established investigators who had received prior NIGMS grants in order to streamline the grant process. Funding could start as early as April 2016. Preusch told BioCentury NIGMS hopes to announce by this summer that it will issue a second set of MIRA awards for new investigators.
For both funding streams, MIRA grants will last a year longer than the average four-year NIGMS grant, and will not be tied to specific projects. Preusch said NIGMS will evaluate the program continuously, and hopes that the grants' flexibility and stability will make them attractive to researchers and serve as a model elsewhere in NIH.
The program was announced last July (see SciBX, Aug. 28, 2014).
Experts agree: antibiotic-resistant bacteria is a growing threat but the pipeline for novel antibiotics has virtually dried up. What's holding back new treatments to combat these infections? Jonathan Kfoury offers solutions to unleash a new wave of antibiotic development by fixing a broken pricing and reimbursement model in L.E.K.'s Executive Insights.