Exelixis Inc. (NASDAQ:EXEL) fell $2.29 (55%) to $1.85 on Tuesday after top-line data showed its Cometriq cabozantinib missed the primary endpoint in the 960-patient Phase III COMET-1 trial to treat metastatic castration-resistant prostate cancer (CRPC) that has progressed following other treatment.
Cometriq led to a median overall survival (OS) of 11 months vs. 9.8 months for prednisone (p=0.212).
Exelixis will now focus on developing cabozantinib for metastatic renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC), for which it is in Phase III testing. Exelixis markets Cometriq in the U.S. to treat progressive, metastatic medullary thyroid cancer (MTC). The spectrum-selective kinase inhibitor of VEGF receptor 2 (KDR/Flk-1; VEGFR-2) and c-Met receptor tyrosine kinase has conditional approval in the EU for progressive, unresectable, locally advanced or metastatic MTC.
On the heels of the COMET-1 miss, Exelixis will reduce headcount by 70%, or about 160, to about 70. With the headcount reduction, Exelixis expects to have sufficient cash to reach top-line data from the METEOR Phase III trial in RCC next year. Exelixis had about $233.5 million in cash on June 30, and posted a six-month operating loss of $126.7 million.
LCZ696 from Novartis AG (NYSE:NVS; SIX:NOVN) led to a 20% reduction in risk on a composite of cardiovascular death or heart failure hospitalization, the primary endpoint, compared with enalapril in the 8,442-patient Phase III PARADIGM-HF trial to treat heart failure in patients with reduced ejection fraction (HF-REF). In the trial, CV death or heart failure hospitalization occurred in 21.8% of patients receiving LCZ696 vs. 26.5% of patients receiving enalapril (p=0.0000002). Enalapril is a generic angiotensin-converting enzyme (ACE) inhibitor.
The data were presented on Saturday at the European Society of Cardiology meeting in Barcelona and published in the New England Journal of Medicine. In March, Novartis stopped the trial early after an interim analysis showed LCZ696 met the primary endpoint, but at the time detailed data were not disclosed (see BioCentury Extra, March 31).
By year end, Novartis plans to complete submission of a rolling NDA to FDA for LCZ696. A European regulatory submission is slated for early next year. The compound is a dual inhibitor of angiotensin II type 2 (AT2) receptor (ATGR2) and neutral endopeptidase (neprilysin; MME; NEP; CD10).
Novartis gained $3.86 to $93.70 in New York on Tuesday on the data.
Regeneron Pharmaceuticals Inc. (NASDAQ:REGN) and partner Sanofi (Euronext:SAN; NYSE:SNY) presented detailed data at the European Society of Cardiology meeting in Barcelona from four Phase III trials of subcutaneous alirocumab (REGN727) to treat hypercholesterolemia. In July, the partners said the human mAb targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) met the primary endpoint in the trials of reducing LDL-C from baseline to week 24, but did not disclose details (see BioCentury Extra, July 30).
In the ODYSSEY LONG TERM trial, alirocumab reduced LDL-C from baseline to week 24 by 61% vs. a 1% increase for placebo and by 57% from baseline to week 52 vs. a 4% increase for placebo (p<0.0001 for both). Additionally, the partners said alirocumab led to a 1.4% rate of adjudicated major CV events vs. 3% for placebo in a post hoc analysis (p<0.01). ODYSSEY LONG TERM trial enrolled patients with hypercholesterolemia at a high or very high CV risk.
In the ODYSSEY COMBO II trial, alirocumab reduced LDL-C from baseline to week 24 by 51% vs. 21% for Zetia ezetimibe from Merck & Co. Inc. (NYSE:MRK) (p<0.001). In the ODYSSEY FH I and FH II trials, alirocumab reduced LDL-C from baseline to week 24 by 49% in each trial vs. a 3-9% increase for placebo (p<0.0001 for both trials). ODYSSEY COMBO II enrolled patients with hypercholesterolemia at high CV risk inadequately controlled on stable statin therapy, while ODYSSEY FH I and FH II enrolled patients with heterozygous familial hypercholesterolemia (heFH) inadequately controlled with lipid-lowering therapy.
By year end, Regeneron and Sanofi plan to submit U.S. and EU regulatory applications for alirocumab. Regeneron was up $9.05 to $359.50 on Tuesday.
Servier (Neuilly-sur-Seine, France) reported data from the SIGNIFY trial showing that its Procoralan ivabradine missed the primary endpoint of reducing the incidence of a composite of cardiovascular death or nonfatal myocardial infarction vs. placebo in 19,102 patients with stable coronary artery disease (CAD) without clinical heart failure. Servier markets the drug in more than 100 countries, including those of the EU, to treat stable angina and chronic heart failure (CHF).
At a median follow-up of 27.8 months, the incidence of the composite endpoint for ivabradine was 6.8% vs. 6.4% for placebo (p=0.2). In a subgroup of patients with activity-limiting angina, ivabradine significantly increased the incidence of the composite endpoint (7.6% vs. 6.5%, p=0.02). Data were presented at the European Society of Cardiology meeting in Barcelona and published in the New England Journal of Medicine.
In May, EMA's Pharmacovigilance Risk Assessment Committee began a safety review of the drug based on preliminary SIGNIFY data. The committee is expected to make final recommendations to EMA's CHMP in November.
Last week, FDA accepted and granted Priority Review to an NDA from Amgen Inc. (NASDAQ:AMGN) for the selective If channel inhibitor to treat CHF. Amgen has exclusive U.S. commercialization rights to ivabradine from Servier. Amgen said data from SIGNIFY were not included in the NDA submission since the trial evaluated patients with CAD without heart failure (see BioCentury Extra, Aug. 27).
Amgen was off $1.42 to $137.96 on Tuesday.
Amgen Inc. (NASDAQ:AMGN) submitted an MAA to EMA for evolocumab (AMG 145), a human mAb against proprotein convertase subtilisin/kexin type 9 (PCSK9), to treat high cholesterol. The application -- the first in the EU for a PCSK9 program -- comes on the heels of the submission last week of a BLA to FDA for evolocumab. Amgen was down $1.42 to $137.96 on Tuesday.
Regeneron Pharmaceuticals Inc. (NASDAQ:REGN) was up $8.98 to $359.50 on the day. The company and partner Sanofi (Euronext:SAN; NYSE:SNY) plan to submit an MAA to EMA for competing PCSK9 inhibitor alirocumab by year end (see above).
Novo Nordisk A/S (CSE:NVO; NYSE:NVO) is discontinuing all inflammatory disease R&D. Novo ended development of its lead compound in the space, NN8226, which is a recombinant human mAb neutralizing IL-20 in Phase II trials to treat rheumatoid arthritis (RA). In February, Novo discontinued development of NN8828, a recombinant human mAb against IL-21 that was in Phase II trials to treat Crohn's disease (CD).
Novo said the decision affects about 400 employees, of which about half will be offered other positions.
Novo said it intends to expand R&D in diabetes and obesity.
HHS's Office of the Assistant Secretary for Preparedness and Response (ASPR) awarded Mapp Biopharmaceutical Inc. (San Diego, Calif.) a $24.9 million, 18-month contract for development and manufacturing of the company's ZMapp Ebola treatment. ASPR has the option to provide an additional $17.4 million.
HHS said ASPR's Biomedical Advanced Research and Development Authority (BARDA) will provide Mapp funds to produce enough ZMapp for both preclinical studies and early human safety trials, with a goal of FDA approval. Mapp could not be reached for comment.
ZMapp combines components of mAbs targeting Ebola glycoproteins GP1 and GP2 from Mapp's MB-003 and ZMab from Defyrus Inc. (Toronto, Ontario).
The news comes days after ZMapp was shown to reverse 100% of advanced Ebola cases in primates (see BioCentury Extra, Aug. 29).
Amgen Inc. (NASDAQ:AMGN) submitted an MAA to EMA for talimogene laherparepvec to treat regionally and distantly metastatic melanoma. In July, Amgen disclosed that it submitted a BLA to FDA for the modified herpes simplex virus type 1 (HSV-1) encoding GM-CSF.
Amgen was down $1.42 to $137.96 on Tuesday.
Alder Biopharmaceuticals Inc. (NASDAQ:ALDR) fell $2.24 (13%) to $14.80 on Tuesday after Bristol-Myers Squibb Co. (NYSE:BMY) discontinued development of clazakizumab (BMS-945429) and returned worldwide rights to Alder. The humanized mAb against IL-6 has completed a Phase IIb trial in patients with moderate to severe rheumatoid arthritis with an inadequate response to methotrexate and is in a Phase IIb trial to treat active psoriatic arthritis, with data slated for November.
Alder said BMS based its decision on a portfolio prioritization rather than new data or technical issues, and that there are no fees associated with the transaction.
Alder plans to continue development of clazakizumab but declined to disclose details. The company was eligible for $894 million in further development, regulatory and sales milestone payments plus royalties from BMS under the companies' 2009 deal.
InterMune Inc. (NASDAQ:ITMN) revealed in an SEC filing that multiple other companies expressed interest in a deal before Roche (SIX:ROG; OTCQX:RHHBY) agreed to acquire InterMune for $74 per share, or $8.3 billion in cash. Only one other suitor issued a proposal.
On July 26, Roche originally bid $70 per share in cash, a 54% premium to InterMune's close of $45.50 on July 25. An undisclosed company discussed a $57 per share cash deal with InterMune on Aug. 1. InterMune rejected both offers.
Roche raised its offer to $74 per share on Aug. 15. InterMune's board accepted the deal on Aug. 22 (see BioCentury Extra, Aug. 25).
InterMune was up $0.04 to $73.49 on Tuesday.
Cancer epigenetics company Epizyme Inc. (NASDAQ:EPZM) said Jason Rhodes resigned as president and CFO, effective Sept. 30. The company said Rhodes is joining an undisclosed VC fund. Prior to joining Epizyme in 2010, Rhodes was VP of business development at Alnylam Pharmaceuticals Inc. (NASDAQ:ALNY).
Epizyme was down $1.47 to $33.02 on Tuesday. The company announced the news after market close.
FDA accepted and granted Priority Review to an NDA from Actavis plc (NYSE:ACT) for eluxadoline (JNJ-270189066) to treat diarrhea and abdominal pain in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). The company said it plans to submit an amendment to the NDA with additional data from an ongoing trial that the company said will extend the PDUFA for eluxadoline to 2Q15 (see BioCentury, Feb. 10).
Actavis gained the locally acting mu opioid receptor agonist and delta opioid receptor antagonist earlier this year through its acquisition of Forest Laboratories Inc. Forest itself gained the compound through its 2014 acquisition of Furiex Pharmaceuticals Inc.
Actavis was up $2.09 to $229.07 on Tuesday.
Chiesi Farmaceutici S.p.A. (Parma, Italy) and A. M. Pappas & Associates launched a new VC firm, Chiesi Ventures, to invest in early stage research on rare and orphan diseases. A. M. Pappas is an investor but said Chiesi is the sole major investor in the new firm. The companies are not disclosing how much capital they committed to Chiesi Ventures, which will have offices in the U.S. and Italy. According to Chiesi Ventures, the firm will typically invest $4-$5 million in seed and series A rounds in preclinical companies that have some proof of concept.
Ophthalmic play Clearside Biomedical Inc. (Alpharetta, Ga.) raised $16 million in a series B round led by new investor RusnanoMedInvest. Existing investors Hatteras Venture Partners; Santen Pharmaceuticals Co. Ltd. (Tokyo:4536); Mountain Group Capital; and Georgia Research Alliance Venture Fund also participated.
By year end, Clearside plans to start Phase II testing of lead compound CLS-1001 to treat macular edema associated with non-infectious uveitis; and CLS-1003 to treat macular edema associated with retinal vein occlusion (RVO).
CLS-1001 is triamcinolone acetonide delivered with Clearside's ocular microinjection platform. CLS-1003 is triamcinolone acetonide in combination with an intravitreal injection of an undisclosed anti-VEGF (see BioCentury, Aug. 5, 2013).
Cancer immunotherapy company Affimed Therapeutics AG (Heidelberg, Germany) set the terms for a planned IPO on NASDAQ and also said it closed a EUR 11.7 million ($15.4 million) series E round. The company plans to sell 6.3 million shares at $11-$13 in the IPO. At the $12 midpoint, Affimed would raise $75 million and be valued at $266.8 million. Affimed investors also have said they may buy up to $24 million in shares in the offering Jefferies; Leerink Partners; BMO Capital; and Trout Capital are underwriters.
The E round came from Affimed's existing investors, including Aeris Capital; BioMedInvest; LSP-Life Sciences Partners; Novo Nordisk A/S (CSE:NVO; NYSE:NVO); and OrbiMed. Additionally, Affimed secured a EUR 10.5 million ($13.8 million) loan from Perceptive Advisors.
Next quarter, Affimed plans to start a Phase IIb trial of lead candidate AFM13 to treat Hodgkin's lymphoma in patients who have relapsed or are refractory to Adcetris brentuximab from Seattle Genetics Inc. (NASDAQ:SGEN) and Takeda Pharmaceutical Co. Ltd. (Tokyo:4502). AFM13 is a tetravalent bispecific human antibody targeting CD30 and CD16.
Tokai Pharmaceuticals Inc. (Cambridge, Mass.) and Viking Therapeutics Inc. (San Diego, Calif.) both set terms for planned IPOs on NASDAQ.
Tokai plans to sell of 5.4 million shares at $13-$15. At $14, the company would raise $75.6 million and would be valued at $290.7 million. Tokai filed to raise up to $75 million in the offering last month. BMO Capital Markets; Stifel; William Blair; and Janney Montgomery Scott are underwriters. Next half, Tokai plans to start Phase III trials of galeterone (TOK-001) to treat castration-resistant prostate cancer (CRPC). The compound is a selective androgen receptor modulator (SARM) and cytochrome P450 17 alpha-hydroxylase/C17, 20 lyase (CYP17) inhibitor.
Viking plans to sell 5 million shares at $10-$12. At $11, the company would raise $55 million and be valued at $167.1 million. Viking filed to raise up to $57.5 million in the offering in July. Oppenheimer; Roth Capital Partners; Craig-Hallum Capital; MLV; and Summer Street are underwriters. Early next year, Viking plans to start a Phase IIb trial of VK0612 for Type II diabetes and a Phase II trial of VK5211 for cancer cachexia. Viking gained the compounds from Ligand Pharmaceuticals Inc. (NASDAQ:LGND) earlier this year.
Clovis Oncology Inc. (NASDAQ:CLVS) proposed late Tuesday to raise $200 million through the sale of senior convertible notes due 2021 in a private placement to institutional investors. Clovis' rucaparib (CO-338) is in the Phase III ARIEL3 trial to treat platinum-sensitive, relapsed ovarian, fallopian tube or primary peritoneal cancer. Clovis has exclusive, worldwide rights to the oral inhibitor of poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 from Pfizer Inc. (NYSE:PFE).
Clovis was up $0.74 to $48.30 on Tuesday.
Sofinnova Partners hired Henrijette Richter as a partner. She was an investment director of Novo Seeds at Novo A/S. Sofinnova Partners has over EUR 1.3 billion ($1.7 billion) under management.
The health subcommittee of the U.S. House of Representative's Energy and Commerce Committee will hold a hearing on Sept. 9 to discuss FDA guidance covering the regulation of laboratory-developed tests. In late July, FDA released a copy of the draft guidance in a notice to Congress, officially marking the agency's plans for a risk-based framework for regulating LDTs (see BioCentury, Aug. 11).
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