Bristol-Myers Squibb Co. (NYSE:BMY) jumped $3.75 to $65.67 on Tuesday after FDA approved an sBLA for Opdivo nivolumab to treat patients with metastatic squamous non-small cell lung cancer (NSCLC) who have progressed on or after platinum-based chemotherapy. The approval came more than three months ahead of the drug's June 22 PDUFA date, and just five days after BMS said FDA accepted the sBLA for review.
In January, BMS stopped the Phase III CheckMate-017 trial early after an independent data monitoring committee concluded that Opdivo met the primary endpoint of improving overall survival compared to docetaxel (9.2 months vs. 6 months) (see BioCentury Extra, Jan. 12, 2015).
In December 2014, FDA approved the human IgG4 mAb against programmed cell death 1 (PDCD1; PD-1; CD279) to treat unresectable or metastatic melanoma in patients previously treated with the company's Yervoy ipilimumab, and if BRAF V600 mutation-positive, Yervoy plus a BRAF inhibitor. That approval also came more than three months before the drug's PDUFA date (see BioCentury Extra, Dec. 22, 2014).
Opdivo was the second PD-1 inhibitor approved in the U.S., after Keytruda pembrolizumab from Merck & Co. Inc. (NYSE:MRK). Merck plans to submit an sBLA to FDA by mid-2015 for Keytruda to treat NSCLC (see BioCentury Extra, Sept. 4, 2014).
BMS has worldwide rights to Opdivo from Ono Pharmaceutical Co. Ltd. (Tokyo:4528), excluding Japan, Korea and Taiwan, where Ono and BMS are partnered. The drug is also under EMA review.
Pharmacyclics Inc. (NASDAQ:PCYC) jumped $6.72 to $237.20 in after-hours trading on Wednesday as rumors intensified that Johnson & Johnson (NYSE:JNJ) has agreed to buy the cancer drug developer.
Pharmacyclics gained $13.71 to $230.48 in regular trading on Wednesday and ended the day with a market cap of $17.5 billion. The company has gained $3.2 billion (22%) in market cap since Feb. 24, before rumors circulated that a deal worth about $18 billion was near (see BioCentury Extra, Feb. 26).
The acquisition would give J&J full rights to Imbruvica ibrutinib. J&J's Janssen Biotech Inc. unit shares U.S. rights with Pharmacyclics, and holds ex-U.S. rights. Pharmacyclics expects Imbruvica sales to reach $1 billion this year (see BioCentury Extra, Jan. 13).
FDA approved Imbruvica for its fourth indication, Waldenstrom's macroglobulinemia (WM), in January. The drug is also approved to treat chronic lymphocytic leukemia (CLL) in patients with 17p deletion and to treat CLL in patients who have received one prior therapy, and has accelerated approval to treat mantle cell lymphoma (MCL) (see BioCentury Extra, Jan. 29).
Bavarian Nordic A/S (CSE:BAVA) gained DKK74.50 (35%) to DKK286 after granting Bristol-Myers Squibb Co. (NYSE:BMY) an exclusive option to license and commercialize Prostvac. The deal, which includes $60 million up front and more than $915 million in milestones, is the largest reported option agreement for a Phase III compound.
Last week, Bavarian Nordic reported survival data from a Phase I trial of Prostvac in combination with BMS's Yervoy ipilimumab in patients with metastatic castration-resistant prostate cancer (mCRPC). The company plans to start Phase II testing of the combination, but did not disclose a timeline (see BioCentury Extra, Feb. 24).
In 2013, Yervoy alone missed the primary endpoint of improving median overall survival vs. placebo in a Phase III trial in mCRPC patients (see BioCentury Extra, Sept. 12, 2013).
BMS can exercise its option, triggering an $80 million payout to Bavarian Nordic, after data become available from an ongoing Phase III trial of Prostvac to treat mCRPC. Robert Ang, SVP of business development at Bavarian Nordic, said the trial could finish as early as 2017 but did not disclose a timeline for the data readout.
Bavarian Nordic is eligible for more than $230 million in development milestones, which would exceed that figure if Prostvac demonstrates superior efficacy in Phase III compared to Phase II. Ang said the milestone structure is "uncapped."
Bavarian Nordic is also eligible for up to $110 million in regulatory milestones and $495 million in sales milestones, plus tiered double-digit royalties.
The companies said they may conduct combination studies of Prostvac with other undisclosed agents from BMS's immuno-oncology portfolio.
Prostvac is a vaccine that targets PSA and contains a Tricom triad of costimulatory molecules -- CD58 (LFA-3), intercellular adhesion molecule-1 (ICAM-1; CD54) and CD80 (B7-1). It has Fast Track designation from FDA to treat asymptomatic or minimally symptomatic mCRPC. BMS markets Yervoy, a human mAb against CTLA-4 receptor, to treat unresectable or metastatic melanoma.
Grifols S.A. (Madrid:GRF; NASDAQ:GRFS) and Alkahest Inc. will collaborate to develop plasma-based therapies to treat cognitive decline in aging and CNS disorders.
Grifols will acquire a 45% stake in Alkahest for $37.5 million in cash, and will receive worldwide commercialization rights to plasma-based CNS products. Alkahest will also receive a $12.5 million payment and research funding, and will be eligible for undisclosed milestones and royalties.
David Bell, Grifols' general counsel, and Thomas Glanzmann, a Grifols director, took seats on Alkahest's board.
Alkahest Chairman and CEO Karoly Nikolich said the company expects data in 1H16 from a clinical study testing the use of blood plasma harvested from young people to treat cognitive decline in patients with mild to moderate Alzheimer's disease (AD). Nikolich said plasma from young mice has been shown to improve cognition in aging mice.
Nikolich said Alkahest plans to start 4-5 additional clinical studies this year, exploring dosing and frequency of administration, as well as the stage of the disease that responds best to young plasma.
On Tuesday, Johnson & Johnson (NYSE:JNJ) said Alkahest is among the first 10 companies at its JLABS incubator in South San Francisco, Calif. (see BioCentury Extra, March 3).
Nikolich said Alkahest received seed funding last year from a Hong Kong family.
Takeda Pharmaceutical Co. Ltd. (Tokyo:4502) promoted President and COO Christophe Weber to CEO, effective April 1. Weber, who succeeds Yasuchika Hasegawa, will retain the title of president and the COO position will be eliminated. Hasegawa will remain chairman.
Weber led a reorganization and implemented a cost-cutting plan after joining Takeda last April.
Baxter International Inc. (NYSE:BAX) acquired SuppreMol GmbH (Martinsried, Germany) for EUR 200 million ($223.9 million).
SuppreMol's lead compound is SM101, a recombinant, soluble, non-glycosylated version of Fc gamma receptor IIb (CD32B; FCGR2B) that has completed Phase IIa trials to treat idiopathic thrombocytopenic purpura (ITP) and systemic lupus erythematosus (SLE). Baxter intends to begin Phase III studies by 2017.
Antibody developer Xoma Corp. (NASDAQ:XOMA) promoted Thomas Burns to CFO from VP of finance. Burnes succeeds Fred Kurland, who plans to retire on April 3.
Cancer company Adaptimmune Ltd. (Abingdon, U.K.) hired Rafael Amado as CMO and Adrian Rawcliffe as CFO, both effective March 16. Amado was SVP and head of oncology R&D at GlaxoSmithKline plc (LSE:GSK; NYSE:GSK). Rawcliffe was SVP of finance of GSK's North American pharmaceuticals business.
China-focused oncology play CASI Pharmaceuticals Inc. (NASDAQ:CASI) appointed Rong Chen as CMO. Chen was VP and head of the China/Hong Kong regulatory Center of Excellence at GSK.
CNS company KemPharm Inc. (Coralville, Iowa) appointed Tracy Woody as CCO. Woody is the founder and managing director of biotech and medical device consultancy TMW Consulting Inc.
Metabolic and cardiopulmonary play PhaseBio Pharmaceuticals Inc. (Morrisville, N.C.) promoted Jonathan Mow to CEO from CBO. He succeeds Christopher Prior, who resigned in October 2014.
Cannabinoid-based therapeutics developer InMed Pharmaceuticals Inc. (CSE:IN; OTCQB:IMLFF) appointed Ado Mohammed as CMO. Mohammed was associate medical director at GW Pharmaceuticals plc (LSE:GWP; NASDAQ:GWPH).
Orexigen Therapeutics Inc. (NASDAQ:OREX) climbed $0.84 (11%) to $8.48 on Wednesday, adding $103.9 million in market cap, as investors overlooked controversy about how interim data were disclosed from the LIGHT cardiovascular outcomes trial of its marketed Contrave naltrexone/bupropion. With more data not expected to be disclosed before 2017, or even later, the market apparently concluded the statistically significant data showing Contrave is the first obesity drug to show a CV benefit will be sufficient to drive the drug's uptake by doctors and patients even without a label change.
Orexigen has added $332.8 million in market cap since Monday's close, and is now valued above $1 billion.
The interim data disclosed Tuesday were reviewed by FDA as part of Orexigen's December 2013 NDA resubmission for Contrave. While the results were not disclosed at the time, the agency voiced concern that Orexigen disclosed the interim analysis to too many people, potentially biasing the trial, and ultimately required a second CV outcomes trial when it approved Contrave last September (see BioCentury, Sept. 22, 2014).
The CV outcomes data 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 data. On the combined incidence of myocardial infarction, stroke and CV mortality compared to placebo, Contrave reduced the risk of major adverse cardiovascular events (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. The interim analysis included 94 MACE events, 25% of the planned study events.
FDA on Tuesday cautioned the preliminary data are "far too unreliable to conclude anything further about the cardiovascular safety of Contrave" (see BioCentury Extra, March 3, 2015).
LIGHT is fully enrolled and Orexigen does not plan to release additional data until the study's completion. The trial is expected to end in 2017. Company spokesperson McDavid Stilwell said the "utility of the study and plans for its future are under discussion."
The second CV outcomes trial is slated to start this year, with data expected in 2022. Stilwell did not disclose whether interim data from the second trial would be released prior to its expected completion, noting the study protocol has not been finalized.
Orexigen also did not discuss the data included in its MAA for the drug, which received a positive CHMP opinion in December.
Renal company Tricida Inc. (South San Francisco, Calif.) raised a $30 million series B round led by existing investor OrbiMed. Existing investors Sibling Capital Ventures and Limulus Venture Partners also participated.
Tricida hopes to submit an IND this year for lead compound TRC101, which it is developing to treat electrolyte imbalances in chronic kidney disease patients.
Tesaro Inc. (NASDAQ:TSRO) raised $173.4 million through the sale of 3.4 million shares at $51 in a follow-on underwritten by Citigroup; Leerink; Deutsche Bank; BMO Capital Markets; Baird; and Mizuho. Tesaro proposed the offering after market close on Monday when its shares were valued at $54.25. The company shed $0.64 to $51.73 on Wednesday.
Tesaro's oral rolapitant (SCH 619734) is under FDA review to prevent chemotherapy-induced nausea and vomiting (CINV), with a Sept. 5 PDUFA date. Tesaro has exclusive, worldwide rights to the neurokinin 1 (NK1) substance P receptor (TACR1) antagonist from Opko Health Inc. (NYSE:OPK; Tel Aviv:OPK).
Harold Varmus said he will step down as director of NIH's National Cancer Institute, effective March 31. Varmus, who has held the position since 2010, intends to establish a research laboratory at Weill-Cornell Medical College.
NCI Deputy Director Douglas Lowy will become acting director on April 1.
FDA will hold a public workshop on April 1 to discuss the development and implementation of clinical outcomes assessments (COAs). Topics will include ways to include patient-centered outcome measures in drug development, standards for use of COAs in drug development, and standards for collaborative development and dissemination of COAs.
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.