Amgen Inc. (NASDAQ:AMGN) said Kyprolis carfilzomib plus dexamethasone met the primary endpoint of superiority over Velcade bortezomib plus dexamethasone in a planned interim analysis of the Phase III ENDEAVOR trial in second-line multiple myeloma. Kyprolis led to median progression-free survival (PFS) of 18.7 months vs. 9.4 months for the Velcade combo, a benefit of 9.3 months (HR=0.53, 95% CI: 0.44, 0.65).
Amgen EVP of R&D Sean Harper said data from ENDEAVOR are consistent with results of the Phase III ASPIRE trial to treat second-line MM. In that study, Kyprolis had a PFS benefit of 8.7 months over Revlimid lenalidomide (26.3 months vs. 17.6 months, p<0.0001).
ENDEAVOR enrolled 929 MM patients who had received at least one prior therapy. Harper said that while the inclusion and exclusion criteria in the two trials were the same, ENDEAVOR ended up enrolling sicker patients, which could explain the lower overall PFS interval seen for Kyprolis in ENDEAVOR.
Cardiac and renal failure rates were higher in the Kyprolis arm vs. Velcade in ENDEAVOR, but Harper said treatment discontinuations and on-study deaths were comparable between the two arms.
Amgen unblinded the PFS data after the analysis showed it had met the primary endpoint. The company will continue to study overall survival (OS) in the trial.
Amgen plans to present additional data from ENDEAVOR at the American Society for Clinical Oncology (ASCO) meeting in Chicago, beginning in May. Amgen intends to include data on peripheral neuropathy, a prespecified secondary endpoint in the trial.
Kyprolis, a selective proteasome inhibitor, was designed to have both efficacy and safety advantages over Velcade, which can cause peripheral neuropathy (see BioCentury, Sept. 9, 2013).
Kyprolis received accelerated approved in 2012 to treat MM in patients who have had at least two prior therapies, including Velcade and Revlimid. Amgen submitted an sNDA last month to FDA for Kyprolis in second-line MM that includes ASPIRE data and could also support conversion to full approval. Amgen said it will discuss the results from ENDEAVOR with FDA to determine next steps.
Amgen is also enrolling patients in the Phase III CLARION trial in first-line MM, another head-to-head study vs. Velcade.
The company gained Kyprolis via the acquisition of Onyx Pharmaceuticals Inc. for $10.4 billion in cash. Sales of the drug have been slow, reaching $306 million in 2014, leading some investors to suggest Amgen overpaid for Onyx.
Amgen gained $1.91 to $159.63 on Monday, adding $1.4 billion in market cap to $121.1 billion. Ligand Pharmaceuticals Inc. (NASDAQ:LGND) picked up $8.51 (15%) to $63.58. Kyprolis uses Captisol technology from Ligand, which is eligible for royalties of 1.5-3%.
Johnson & Johnson (NYSE:JNJ) and Takeda Pharmaceutical Co. Ltd. (Tokyo:4502) market Velcade, while Celgene Corp. (NASDAQ:CELG) markets Revlimid. -- Erin McCallister, Senior Editor
Pacira Pharmaceuticals Inc. (NASDAQ:PCRX) shed $22.47 (20%) to $92.30 on Monday after it received a complete response letter from FDA for an sNDA for Exparel bupivacaine as a nerve block to provide postsurgical analgesia. The company plans to meet with FDA to discuss the CRL, but declined to disclose a timeline or the nature of FDA's concerns.
Pacira markets the bupivacaine liposome extended-release injectable suspension using DepoFoam drug delivery technology for postoperative pain management. Exparel's 4Q14 sales were $59 million, representing 95% of Pacira's total revenues. Pacira said last week it expected Exparel revenues of $310-$330 million in 2015, with 10% attributed to the nerve block indication.
Athersys Inc. (NASDAQ:ATHX) jumped $0.36 (14%) to $2.95 on Monday after granting Chugai Pharmaceutical Co. Ltd. (Tokyo:4519) Japanese rights to develop and commercialize its MultiStem cell therapy for ischemic stroke.
Athersys will receive $10 million up front and is eligible for $45 million in development and commercial milestones; Y17.5 billion ($145.3 million) in sales milestones; and tiered, double-digit royalties.
William Lehmann, Athersys' president and COO, told BioCentury that Chugai's clinical trial design and timeline in Japan will depend on results from an ongoing U.S. and European Phase II trial of MultiStem to treat stroke. The companies expect those data in 4-6 weeks.
Athersys is developing MultiStem for multiple indications. The therapy, which consists of allogeneic multipotent adult progenitor cells (MAPC) obtained from the bone marrow of healthy adult donors, has Orphan Drug designation in the U.S. and EU to prevent graft-versus-host disease and in the U.S. to treat mucopolysaccharidosis I (MPS I; Hurler syndrome).
Last year, MultiStem missed the co-primary endpoints in a Phase II trial to treat moderate to severe ulcerative colitis (UC) (see BioCentury Extra, April 28, 2014).
Kite Pharma Inc. (NASDAQ:KITE) and NIH's National Cancer Institute expanded a 2012 Cooperative Research and Development Agreement (CRADA) to include immunotherapies against neo-antigens and additional undisclosed T cell receptor (TCR) and chimeric antigen receptor (CAR) T cell candidates targeting solid tumors.
Under the amended deal, the partners will develop methods to rapidly identify candidates targeting neo-antigens and optimize manufacturing of the candidates. Neo-antigens are tumor-specific antigens that arise as tumors accumulate genetic mutations.
Kite said the TCR candidates are engineered with retroviruses to target tumor antigens and include therapies for colorectal and lung cancers.
Kite increased its quarterly payment to NCI to $750,000 from $250,000. Kite declined to give details about the TCR and CAR T candidates or their clinical timelines.
Under the 2012 CRADA, Kite gained access to NCI's autologous T cell technology to treat hematological and solid cancers, and obtained an exclusive option to license any products arising from the collaboration (see BioCentury, Feb. 4, 2013).
Kite fell $1.32 to $64.12 on Monday.
Amgen Inc. (NASDAQ:AMGN) granted Celimmune LLC (Bethesda, Md.) exclusive, worldwide rights outside of Japan to develop and commercialize AMG 714, a human mAb against IL-15. Amgen has an exclusive option to reacquire AMG 714 after Celimmune completes additional clinical trials. Both companies declined to disclose details of the deal, including financial terms.
Celimmune is planning Phase II trials of the candidate to treat diet non-responsive celiac disease and refractory celiac disease (RCD). The company declined to give a development timeline.
Amgen discontinued development of AMG 714 in 2008 after it did not show efficacy in Phase I and Phase II trials to treat psoriasis and rheumatoid arthritis.
Celimmune, which announced last week that it had begun operations, declined to disclose its investors.
Atara Biotherapeutics Inc. (NASDAQ:ATRA) gained $0.92 to $20.48 after its partner, Memorial Sloan Kettering Cancer Center, received breakthrough therapy designation for EBV-CTL to treat rituximab-refractory lymphoproliferative disease associated with Epstein-Barr virus (EBV), which can occur after allogeneic hematopoietic cell transplantation (HCT).
Atara has an exclusive, worldwide option to develop and commercialize EBV-CTL, T cells against EBV, and two additional allogeneic T cell therapy programs under a 2014 deal.
The European Commission approved an MAA for Xydalba dalbavancin from Actavis plc (NYSE:ACT) to treat acute bacterial skin and skin structure infections (ABSSSIs) in adults. The approval triggers a $1 contingent value right (CVR) payment to shareholders of Durata Therapeutics Inc., which Actavis acquired last year (see BioCentury Extra, Oct. 6, 2014).
Actavis markets the second-generation glycopeptide antibiotic in the U.S. as Dalvance to treat ABSSSIs caused by susceptible Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA).
Actavis gained $5.95 to $297.31 on Monday.
Array BioPharma Inc. (NASDAQ:ARRY) promoted Andrew Robbins to COO from SVP of commercial operations. Robbins will succeed David Snitman, who will serve as EVP of business development until he retires in June.
NGM Biopharmaceuticals Inc. (South San Francisco, Calif.) named Jeff Jonker as president and David Woodhouse as CFO. Jonker was SVP of corporate and business development at Theravance Biopharma Inc. (NASDAQ:TBPH) and Theravance Inc. (NASDAQ:THRX). Woodhouse was managing director and co-head of U.S. biotechnology investment banking at Goldman Sachs.
Medivir AB (SSE:MVIR B) hired Ola Burmark as CFO and Christine Lind as EVP of strategic business development. Burmark was CFO at OneMed AB (Danderyd, Sweden). Lind was VP of business development at LifeCell Corp. (Branchburg, N.J.).
diaDexus Inc. (OTCQB:DDXS) named Leone Patterson CFO. Patterson was CFO at Transcept Pharmaceuticals Inc., which reverse-merged with Paratek Pharmaceuticals Inc. (NASDAQ:PRTK) last year.
Incyte Corp. (NASDAQ:INCY) hired Steven Stein as SVP and CMO. Stein was formerly SVP of U.S. clinical development and medical affairs at the Novartis Oncology U.S. unit of Novartis AG (NYSE:NVS; SIX:NOVN).
Eyegate Pharmaceuticals Inc. (OTCQB:EYEG) appointed Michael Raizman as consulting CMO. Raizman is director of cornea and cataract service at the New England Eye Center and associate professor of ophthalmology at Tufts University School of Medicine.
Ipsen Group (Euronext:IPN; Pink:IPSEY) hired Dominique Laymand as SVP, chief ethics and compliance officer, effective March 16. Laymand was previously VP of compliance and ethics at Bristol-Myers Squibb Co. (NYSE:BMY).
Portola Pharmaceuticals Inc. (NASDAQ:PTLA) rose $2.68 to $40.76 on Monday after reporting full data from the first part of the Phase III ANNEXA-R study, in which anticoagulant antidote andexanet alfa met all primary and secondary endpoints.
Portola said an IV bolus of andexanet alfa rapidly and significantly reversed the anticoagulant activity of Xarelto rivaroxaban from Bayer AG (Xetra:BAYN) and partner Johnson & Johnson (NYSE:JNJ) compared to placebo (p<0.0001), the trial's primary endpoint. The candidate also reduced the concentration of unbound Xarelto in the plasma (p<0.0001) and restored thrombin levels to the normal range in 26 out of 27 patients. The company reported top-line results in January (see BioCentury Extra, Jan 9).
Portola expects data in mid-2015 from the second part of the trial, which will assess a bolus followed by a continuous infusion. The company expects to submit a BLA by YE15. The recombinant protein that reverses the anticoagulant activity of Factor Xa inhibitors has breakthrough therapy and Orphan Drug designations.
Mersana Therapeutics Inc. (Cambridge, Mass.) raised $35 million in a series B-1 round led by existing investor New Enterprise Associates and named Anna Protopapas president and CEO.
New investors Rock Springs Capital and Elliott Sigal, a venture partner at NEA and former EVP at Bristol-Myers Squibb Co. (NYSE:BMY), also participated, as did existing investors Pfizer Venture Investments and Fidelity Biosciences.
Protopapas was president of the Millennium Pharmaceuticals Inc. subsidiary of Takeda Pharmaceutical Co. Ltd. (Tokyo:4502). She and Elaine Jones, executive director of Pfizer Venture Investments, joined Mersana's board.
Mersana said it plans to file an IND by YE15 for its first antibody-drug conjugate (ADC) using its Fleximer polymer technology. It intends to disclose more details about the candidate later this year.
In 2012, the company shifted its focus to ADCs and recapitalized with a $27 million series A-1 round; it had previously been developing small molecule conjugates (see BioCentury Extra, July 31, 2012).
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.