The Daily Extra

Royalty ups bid as Elan unveils deals

Mon, 20 May 2013 17:23:37 -0700

Royalty Pharma (New York, N.Y.) raised its offer to acquire Elan Corp. plc (NYSE:ELN) on Monday shortly after Elan announced a flurry of proposed moves, including two proposed acquisitions, a spinout, a share buyback and an $800 million note deal. Royalty increased its bid to $12.50 per share from $11.25, valuing Elan at $6.4 billion. The bid is contingent on Elan shareholders rejecting Monday's deals, as well as this month's proposed deal to pay Theravance Inc. (NASDAQ:THRX) $1 billion in cash in exchange for a 21% interest in the royalties Theravance is eligible to receive from partner GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) for four respiratory programs (see BioCentury, May 20).

Elan plans to raise the $800 million through the sale of senior notes due 2021, and said it will repurchase $200 million in shares under a new buyback program. Elan also proposing to buy rare disease company AOP Orphan Pharmaceuticals AG (Vienna, Austria) and acquire a 48% stake in NewBridge Pharmaceuticals Ltd. (Dubai, UAE). It also plans to spin out ELND005 into a newco (see below). Elan expects to have about $1.2 billion in pro forma cash following the deals, all of which are subject to shareholder approval at a June 17 extraordinary general meeting.

Elan was up $0.37 to $12.04 on Monday. Theravance was off $2.58 to $37.01.

Elan to buy AOP, NewBridge stake, spin out ELND005

Mon, 20 May 2013 17:23:37 -0700

Elan Corp. plc (NYSE:ELN) announced two proposed acquisitions on Monday, including a proposal to buy rare disease company AOP Orphan Pharmaceuticals AG (Vienna, Austria) for EUR 175.7 million ($225.5 million) in cash and EUR 87.8 million ($112.7 million) in Elan shares, plus up to EUR 270 million ($346.5 million) in milestones. AOP had 2012 revenues of about EUR 59 million ($75.7 million), according to Elan. The company also said it will pay $40 million to acquire a 48% stake in NewBridge Pharmaceuticals Ltd. (Dubai, UAE), which in-licenses products approved in the U.S., Europe and Japan to commercialize in the Middle East, Africa, Turkey and Caspian regions. Elan will have an option to acquire the remaining stake in NewBridge for $244 million by 2015.

Additionally Elan said it will spin out ELND005 -- which is in Phase II testing to treat agitation and aggression in patients with Alzheimer's disease (AD) and for the maintenance treatment of bipolar I disorder -- into newco Speranza Therapeutics Ltd. Elan will provide $70 million in funding, plus up to an additional $8 million. Elan CMO Menghis Bairu will be CEO of Speranza. Elan is developing ELND005, a small molecule that disaggregates beta amyloid fibrils, with Transition Therapeutics Inc. (TSX:TTH; NASDAQ:TTHI) under an amended 2006 deal.

The proposed deals came alongside plans for an $800 million note deal and a $200 million share buyback, as well as an increased bid from Royalty Pharma (New York, N.Y.) to acquire Elan (see above).

On Monday, Elan was up $0.37 to $12.04.

Actavis to acquire Warner Chilcott

Mon, 20 May 2013 17:23:37 -0700

Generics company Actavis Inc. (NYSE:ACT) will acquire specialty pharma Warner Chilcott plc (NASDAQ:WCRX) in a stock deal that values Warner Chilcott at about $5 billion. Warner Chilcott shareholders will receive 0.16 Actavis shares per Warner Chilcott share held or about $17.09 per share based on Actavis' close of $106.81 on May 9, before the companies announced they were in negotiations to merge. Actavis will also assume about $3.4 billion of Warner Chilcott's net debt (see BioCentury Extra, May 10).

The deal, which has been approved by the boards of both companies and is subject to shareholder approval, is slated to close by year end. Warner Chilcott shareholders will own about 23% of the new company, which will be named Actavis plc and be incorporated in Ireland. BofA Merrill Lynch and Greenhill are advising Actavis; Deutsche Bank is advising Warner Chilcott.

Actavis reported $5.9 billion in 2012 revenues, and Warner Chilcott reported $2.5 billion. On Monday, Actavis was up $1.65 to $127.15. Warner Chilcott was up $0.39 to $19.60 on the day.

FDA reviewers question safety of Merck's suvorexant

Mon, 20 May 2013 17:23:37 -0700

FDA reviewers said insomnia candidate suvorexant from Merck & Co. Inc. (NYSE:MRK) is effective at promoting sleep, but questioned the product's safety profile as well as the pharma's proposed dosing levels. In briefing documents released ahead of Wednesday's Pulmonary-Allergy Drugs Advisory Committee meeting to discuss an NDA for the dual orexin receptor antagonist, the reviewers said suvorexant doses that are lower than those proposed by Merck may offer similar efficacy and better safety. The reviewers noted that fewer patients received the lower doses in clinical trials.

The reviewers also outlined their suvorexant safety concerns, including daytime somnolence, narcolepsy-like syndrome and suicidal ideation. The lowest dose of suvorexant for which Merck is seeking approval is 15 mg, but the reviewers note that, "if a dosage strength lower than 15 mg is unavailable, we would need to consider if the drug could be marketed safely at all, if we believe that a substantial proportion of the indicated population needs a lower dose." FDA is asking the committee to discuss whether a 10 mg dose would be an "appropriate recommendation as a starting dose." The questions also note that FDA believes the 15 mg dose "results in excessive suvorexant exposure" in some populations, including obese women and patients taking metabolic inhibitors.

Merck has not disclosed the PDUFA date for suvorexant; a standard review would put the PDUFA date in September.

Effector raises $45M in tranched series A

Mon, 20 May 2013 17:23:37 -0700

Effector Therapeutics Inc. (San Diego, Calif.) raised $45 million in a tranched series A round co-led by U.S. Venture Partners; Abingworth; Novartis Venture Funds; and SR One. Astellas Venture Management; Osage University Partners; and Mission Bay Capital also participated. Effector, which declined to disclose details of the tranches, plans to develop small molecules to selectively regulate translation of oncogenes for cancer indications.

Abingworth's Ken Haas, Novartis Venture Funds' Markus Goebel and SR One's Simeon George joined Effector's board. The newco also appointed Carol Gallagher as chairman. Gallagher was CEO of Calistoga Pharmaceuticals Inc., which Gilead Sciences Inc. (NASDAQ:GILD) acquired in 2011.

Karyopharm raises $48.2 million in series B

Mon, 20 May 2013 17:23:37 -0700

Cancer company Karyopharm Therapeutics Inc. (Natick, Mass.) raised $48.2 million in a series B round led by an undisclosed private investor. New investor Delphi Ventures and additional undisclosed investors participated. Delphi Ventures' Deepa Pakianathan will join Karyopharm's board.

Karyopharm's KPT-330 is in Phase I testing to treat advanced hematologic malignancies and solid tumors, with data slated to be presented at the American Society of Clinical Oncology meeting later this month. The company plans to start pivotal trials of the oral selective inhibitor of nuclear export (SINE) protein exportin 1 (XPO1;CRM1) in at least two indications in 1H14.

Ironwood, NPS planning follow-ons

Mon, 20 May 2013 17:23:37 -0700

Ironwood Pharmaceuticals Inc. (NASDAQ:IRWD) and NPS Pharmaceuticals Inc. (NASDAQ:NPSP) both announced plans late Monday to raise money in follow-ons. Ironwood proposed to sell 10.5 million shares in a follow-on underwritten by JPMorgan; BofA Merrill Lynch; and Morgan Stanley. If sold at Ironwood's close on Monday of $13.83, the company would raise $145.2 million. Ironwood and partner Forest Laboratories Inc. (NYSE:FRX) launched Linzess linaclotide in the U.S. in December to treat irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC). The European Commission approved the guanylate cyclase C (GCC; GUCY2C) agonist for IBS-C in November.

NPS plans to sell 6 million shares in a follow-on underwritten by JPMorgan and Morgan Stanley. If sold at NPS's Monday close of $14.11, the company would raise $84.7 million. NPS markets Gattex teduglutide in the U.S. to treat short bowel syndrome. Earlier this month, the company reported $654,000 in the first quarter sales of the analog of glucagon-like peptide-2 (GLP-2), which NPS launched in February (see BioCentury, March 25).

Ironwood was off $0.56 on Monday, while NPS was off $0.17.

NanoString files for IPO

Mon, 20 May 2013 17:23:37 -0700

Diagnostics company NanoString Technologies Inc. (Seattle, Wash.) filed to raise up to $86.3 million in an IPO underwritten by JPMorgan; Morgan Stanley; Leerink; and Baird. Earlier this year, NanoString launched its Prosigna Breast Cancer Prognostic Gene Signature Assay in the EU and Israel to subtype breast cancer tumor and estimate the probability of cancer recurrence in postmenopausal women. The intrinsic subtying assay runs on NanoString's marketed nCounter Analysis System, an automated system for digital gene expression analysis, and uses the PAM50 gene signature, to which NanoString has exclusive, worldwide rights from Bioclassifier LLC (St. Louis, Mo.).

Athyrium, Neuberger close $507M fund

Mon, 20 May 2013 17:23:37 -0700

Athyrium Capital Management and partner Neuberger Berman closed a life sciences private credit fund, Athyrium Opportunities Fund L.P., at $507 million, well above the original target of $350 million. The fund, which the partners formed in 2011, makes structured investments -- including loans, royalties or royalty-backed investments and debt -- in the healthcare and life science sectors, with a focus on public and private companies with approved products, royalty income or direct product sales. The fund will commit $25-$75 million in financings in small- to medium-sized companies including pharmaceutical, medical device and diagnostic companies in the U.S., Europe and Asia. The fund has already made five investments representing 20% of the committed capital.

Pfizer discontinues Phase III of inotuzumab for NHL

Mon, 20 May 2013 17:23:37 -0700

Pfizer Inc. (NYSE:PFE) said it discontinued the Phase III B1931008 trial evaluating inotuzumab ozogamicin to treat relapsed or refractory CD22-positive aggressive non-Hodgkin's lymphoma. The move came after an interim analysis by an independent DMC showed once-monthly inotuzumab ozogamicin plus rituximab would not meet the primary endpoint of improving overall survival (OS) vs. investigator's choice of rituximab plus either bendamustine or gemcitabine. The open-label trial was slated to enroll about 377 patients who are not candidates for intensive high-dose chemotherapy.

Pfizer said it will review the data to determine if there are subsets of patients that benefited from treatment with inotuzumab ozogamicin, a humanized mAb against CD22 linked to the calicheamicin cytotoxin. The pharma said it will also continue to evaluate the product in the Phase III INO-VATE ALL (B1931022) trial to treat adults with relapsed or refractory CD22-positive acute lymphoblastic leukemia (ALL). Pfizer, which announced the news late Monday, is co-developing inotuzumab ozogamicin with UCB Group (Euronext:UCB), which was up EUR 0.11 to EUR 44.56 on the day.

Biogen Idec Inc. (NASDAQ:BIIB) and Genentech Inc., a unit of Roche (SIX:ROG; OTCQX:RHHBY), co-market rituximab as Rituxan in the U.S., while Roche markets it as MabThera elsewhere. Cephalon Inc., which Teva Pharmaceutical Industries Ltd. (NASDAQ:TEVA) acquired in 2011, markets bendamustine as Treanda.

XenoPort discontinues arbaclofen placarbil program

Mon, 20 May 2013 17:23:37 -0700

XenoPort Inc. (NASDAQ:XNPT) fell $1.03 (15%) to $5.72 on Monday after discontinuing development of arbaclofen placarbil based on top-line data showing that twice-daily doses of the product missed the co-primary endpoints in a Phase III trial to treat spasticity in multiple sclerosis (MS) patients. XenoPort had an SPA from FDA for the trial, which enrolled 228 patients. In 2011, XenoPort discontinued development of arbaclofen placarbil -- a transported prodrug of R-baclofen, a GABA B receptor agonist -- to treat gastroesophageal reflux disease (GERD) (see BioCentury, May 23, 2011).

XenoPort markets Horizant gabapentin enacarbil, a transported prodrug of gabapentin, to treat restless legs syndrome (RLS) and to manage postherpetic neuralgia (PHN). The company's next most advanced product is XP21279, a sustained-release transported prodrug of L-dopa in Phase II testing to treat Parkinson's disease (PD).

Aduro's CRS-207 meets in Phase II for pancreatic cancer

Mon, 20 May 2013 17:23:37 -0700

Aduro BioTech Inc. (Berkeley, Calif.) stopped early a Phase II trial evaluating CRS-207 plus GVAX Pancreas cancer vaccine and cyclophosphamide to treat pancreatic cancer after the combination met the primary endpoint of improving overall survival (OS) vs. GVAX Pancreas and cyclophosphamide alone (6 vs. 3.4 months, p=0.0114). The open-label, U.S. trial enrolled 90 patients with metastatic pancreatic ductal adenocarcinoma (PDA) who received or refused one or more prior chemotherapy regimen. Data are slated to be presented at the American Society of Clinical Oncology meeting in June. Aduro declined to disclose next steps for CRS-207, a live attenuated strain of Listeria monocytogenes that expresses human mesothelin.

Earlier this year, Aduro acquired all assets related to GVAX cancer vaccines from BioSante Pharmaceuticals Inc. (NASDAQ:BPAX). Aduro already had rights to GVAX vaccines to treat pancreatic and prostate cancer. GVAX Pancreas, which has completed a Phase II trial to treat operable pancreatic cancer, is an allogeneic cancer vaccine engineered to secrete GM-CSF.

Lundbeck, Takeda report more Phase III MDD data

Mon, 20 May 2013 17:23:37 -0700

H. Lundbeck A/S (CSE:LUN) and partner Takeda Pharmaceutical Co. Ltd. (Tokyo:4502) presented additional data on Monday showing that some doses of Brintellix vortioxetine significantly improved depression rating scores while other doses did not in four Phase III trials for the acute treatment of major depressive disorder (MDD). An NDA for the serotonin modulator and stimulator is under FDA review to treat MDD, with an Oct. 2 PDUFA date. An MAA for the product is also under review for the indication in Europe. Lundbeck said both the NDA and MAA include a 5-20 mg Brintellix dose range. Data from all of the trials are included in the applications.

In Study 315, once-daily 20 mg Brintellix met the primary endpoint of reducing Montgomery-Asberg Depression Rating Scale (MADRS) scores from baseline to week eight vs. placebo (p=0.023), while a once-daily 15 mg dose missed the endpoint (p-value not disclosed). In Study 13267A, once-daily 15 and 20 mg doses of Brintellix each met the primary endpoint (p<0.0001 for both), while in Study 316 once-daily 20 mg Brintellix met (p=0.002) but once-daily 10 mg missed the primary endpoint (p=0.58). In Study 317, once-daily 10 and 15 mg doses of Brintellix each missed the primary endpoint (p-values not disclosed). The double-blind trials enrolled 2,141 patients aged 18-75. Data from all the trials were presented at the American Psychiatric Association meeting in San Francisco.

Lundbeck partnered with Takeda to co-develop and co-commercialize Brintellix in the U.S. and Japan in 2007. On Monday, Lundbeck was unchanged at DKK115.80.

FDA to discuss HIV at second patient-focused meeting

Mon, 20 May 2013 17:23:37 -0700

FDA will hold a public meeting on June 14 to discuss HIV, including the impact of HIV on daily life and experience with currently available therapies, as well as patient views on issues related to HIV cure research, including perceived benefits and acceptable risk. The meeting is the second under FDA's Patient-Focused Drug Development initiative, under which the agency is holding public meetings on a range of disease areas to discuss topics including the impact of the disease, the measures of benefit that matter most to patients and the adequacy of existing treatment options.

Last month, FDA released a list of 16 disease areas for which it will hold the first round of public meetings in FY13-15 (see BioCentury, May 6).

Sanofi's SAR302503 meets in myelofibrosis

Fri, 17 May 2013 00:00:00 -0700

Sanofi (Euronext:SAN; NYSE:SNY) said once-daily 400 and 500 mg doses of oral SAR302503 each met the primary endpoint in the Phase III JAKARTA trial to treat primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF) and post-essential thrombocythemia myelofibrosis (PET-MF). Specifically, both doses improved the proportion of patients with a 35% or greater reduction in spleen volume from baseline to week 24 vs. placebo. The double-blind, international trial enrolled 289 patients with intermediate-2 or high-risk PMF, PPV-MF or PET-MF.Sanofi said it plans to submit regulatory applications for SAR302503 in the indication, but said it is "premature to comment" on a potential time frame. The pharma, which gained the selective oral Janus kinase-2 (JAK-2) inhibitor through its 2010 acquisition of TargeGen Inc., has an SPA from FDA for the JAKARTA trial.Incyte Corp. (NASDAQ:INCY), which markets an oral JAK-1 and JAK-2 inhibitor to treat myelofibrosis, was down $0.13 to $23.04 on Friday. The company's ruxolitinib is approved in the U.S. as Jakafi and in the EU as Jakavi. Novartis AG (NYSE:NVS; SIX:NOVN) has exclusive ex-U.S. rights to the product from Incyte under a 2009 deal.Separately, Sanofi said it will explore three options, including the establishment of local start-ups, to transform its research facility in Toulouse, France, over the next five years under a restructuring of its French operations announced last year (see BioCentury, April 29).

Novo reports Phase III data for hemophilia B compound

Fri, 17 May 2013 00:00:00 -0700

Novo Nordisk A/S (CSE:NVO; NYSE:NVO) reported data on Friday from the 74-patient Phase III paradigm 2 trial evaluating N9-GP -- a glyco-pegylated derivative of recombinant human Factor IX -- to treat and prevent bleeding episodes in patients with hemophilia B. Once-weekly 10 and 40 U/kg doses of N9-GP as prophylaxis for 12 months reduced median annualized bleeding rates compared to on-demand treatment with N9-GP for six months (2.9 and 1 episode per year, respectively, vs. 15.6 episodes per year). According to clinicaltrials.gov, the primary endpoint of the trial was incidence of inhibitory antibodies against Factor IX. Novo Nordisk declined to disclose details. The company plans to complete the remaining two Phase III trials of N9-GP in the paradigm program in pediatric patients and in patients undergoing surgery within the next 12 months. Novo Nordisk plans to submit regulatory applications for the product in 2015.

ThromboGenics' ocriplasmin misses in wet AMD trial

Fri, 17 May 2013 00:00:00 -0700

ThromboGenics N.V. (Euronext:THR) disclosed in a business update for the period ending April 30 that ocriplasmin missed the primary endpoint in the Phase IIa MIVI-5 trial to treat focal vitreomacular adhesion (VMA) associated with wet age-related macular degeneration (AMD). Specifically, a single injection of ocriplasmin plus anti-VEGF treatment missed the primary endpoint of a greater proportion of patients achieving complete resolution of their focal VMA at day 28 vs. sham control plus anti-VEGF treatment (24% vs. 12%, p=0.26). ThromboGenics said it is discussing future development plans for ocriplasmin in the indication with the Alcon Inc. ophthalmic unit of Novartis AG (NYSE:NVS; SIX:NOVN), which has ex-U.S. rights to commercialize the recombinant microplasmin, a truncated form of the natural human protein plasmin. Ocriplasmin is approved in the EU to treat vitreomacular traction, including when associated with a macular hole of 400 µm or less in diameter; and in the U.S. to treat symptomatic VMA, which causes vitreomacular traction. ThromboGenics, which launched the drug in the U.S. in mid-January, also reported U.S. sales of over $10 million through the end of April for Jetrea. Novartis launched ocriplasmin in the EU this quarter. On Friday, ThromboGenics was off EUR 2.81 to EUR 34.35.

Bayer submits Japanese application for riociguat

Fri, 17 May 2013 00:00:00 -0700

Bayer AG (Xetra:BAYN) submitted a regulatory application in Japan for riociguat to treat chronic thromboembolic pulmonary hypertension (CTEPH). The oral soluble guanylyl cyclase (sGC) stimulator is under Priority Review in the U.S. to treat pulmonary arterial hypertension (PAH) and inoperable CTEPH or persistent/recurrent CTEPH after pulmonary endarterectomy (PEA), a surgical treatment. Bayer submitted the NDA in February. An eight-month Priority Review would place the PDUFA date in October; the specific date is not disclosed.

TaiGen submits nemonoxacin applications in Taiwan, China

Fri, 17 May 2013 00:00:00 -0700

TaiGen Biotechnology Co. Ltd. (Taipei, Taiwan) submitted a pair of NDAs in Taiwan and China for oral nemonoxacin to treat community-acquired pneumonia (CAP). The company, which said these are the first applications submitted worldwide, expects a decision in 1H14. An IV formulation of nemonoxacin is in Phase II testing to treat moderate to severe CAP, while TaiGen also has completed a Phase II trial of the oral formulation in diabetic foot infections. The company has exclusive, worldwide rights to the non-fluorinated quinolone antibiotic topoisomerase inhibitor from Warner Chilcott plc (NASDAQ:WCRX) under a 2011 deal.

G-BA rebuffs Pixuvri, Trajenta for second indication

Fri, 17 May 2013 00:00:00 -0700

Germany's Federal Joint Committee (G-BA) issued a final benefit assessment rebuffing diabetes drug Trajenta linagliptin from Boehringer Ingelheim GmbH (Ingelheim, Germany) as add-on therapy to insulin with or without metformin to treat Type II diabetes -- an indication approved by the European Commission last year. G-BA said the xanthine-based dipeptidyl peptidase-4 (DPP-4) as add-on therapy to insulin provides "no additional benefit" over human insulin and metformin, G-BA's requested comparator, because the company did not submit "necessary evidence." The decision is in line with a preliminary assessment G-BA issued in March (see BioCentury, March 18). Boehringer and partner Eli Lilly and Co. (NYSE:LLY) do not market Trajenta in Germany. Separately, G-BA issued a final benefit assessment saying that cancer drug Pixuvri pixantrone from Cell Therapeutics Inc. (NASDAQ:CTIC; Milan:CTIC) provides "no additional benefit" over patient-individualized care, G-BA's requested comparator, because the company did not submit suitable data. In March, Germany's Institute for Quality and Efficiency in Health Care (IQWiG) said in a preliminary benefit assessment that Pixuvri provides "no additional benefit" (see BioCentury Extra, March 1).Drugs that do not have an additional benefit are added to the reference pricing system, which gives a similar base price to all comparable drugs. If there is no reference, the company will negotiate a price no higher than that of the comparator. Cell Therapeutics was up a penny to $1.16 on Friday.

Kamada amends NASDAQ offering

Fri, 17 May 2013 00:00:00 -0700

Kamada Ltd. (Tel Aviv:KMDA) said it now plans to raise about $60 million through the sale and listing of 5.6 million shares on NASDAQ in a follow-on. The company also added RBC Capital Markets; Oppenheimer; and Chardan Capital Markets as underwriters. Morgan Stanley and Jefferies are lead underwriters. Kamada filed the offering, which it expects to price the week of May 27, in April. Kamada develops and markets plasma-derived protein therapeutics, including Glassia, an IV formulation of alpha-1 antitrypsin (AAT) that partner Baxter International Inc. (NYSE:BAX) markets in the U.S. to treat AAT deficiency. The Tel Aviv Stock Exchange was closed Friday.

Sen. Coburn warns of 'IPAB-of-One'

Fri, 17 May 2013 00:00:00 -0700

A legal analysis released Thursday by Sen. Tom Coburn (R-Okla.) indicates that if members of Congress fail to confirm members of a controversial Medicare cost-containment board, HHS Secretary Kathleen Sebelius would be empowered to formulate and implement Medicare cuts. Coburn, a strong opponent of the Independent Payment Advisory Board (IPAB) and the Affordable Care Act that created it, said that under this scenario Sebelius would become an "IPAB-of-One." The Affordable Care Act specifies that 12 of IPAB's 15 members are to be appointed based on consultations with the Speaker of the U.S. House of Representatives and the minority leader, and the Senate majority and minority leaders. The remaining three members are appointed by the President. All members must be confirmed by the Senate. Earlier this month, House Speaker John Boehner (R-Ohio) and Senate Minority Leader Mitch McConnell (R-Ky.) sent President Obama a letter declining to appoint IPAB members (see BioCentury Extra, May 10).Starting in FY15, IPAB is required to submit a proposal to Congress in any fiscal year in which Medicare costs exceed a threshold established by the Affordable Care Act. If IPAB doesn't submit a proposal for any reason -- including failure of the Senate to confirm members -- the HHS Secretary must submit her own proposal, according to the legal analysis. The recommendations -- whether from IPAB or the HHS Secretary -- would automatically go into effect unless Congress enacted equivalent cuts.

Democratic Reps. reintroduce clinical transparency bill

Fri, 17 May 2013 00:00:00 -0700

A group of Democrats in the U.S. House of Representatives reintroduced a bill, H.R. 2031, that would impose stronger reporting requirements on the U.S. clinical trial registry data bank, clinicaltrials.gov. The Trial and Experimental Studies Transparency (TEST) Act would require all human trials to be registered before enrollment of the first subject and also would require publication of the trial protocol prior to the trial start, as well as the publication on clinicaltrials.gov within one year of trial completion. It also would require all foreign trials to meet the same registration and reporting requirements as U.S. trials if they are used to support a marketing application in the U.S. The same group of representatives introduced a version of the bill during the last Congressional session, but that bill, H.R. 6272, was never voted out of the Energy and Commerce Committee's health subcommittee. In February, GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) became the first pharma to publicly support the AllTrials campaign, which is calling for the disclosure of clinical trial results and clinical study reports -- which are formal reports that provide details on the design, methods and results of trials and may also form the basis of regulatory applications -- to increase trial transparency (see BioCentury This Week, April 14).

Gilead reports Phase II data for idelalisib

Thu, 16 May 2013 00:00:00 -0700

Gilead Sciences Inc. (NASDAQ:GILD) said twice-daily oral idelalisib plus rituximab led to an overall response rate (ORR) of 97% in the 64-patient Phase II Study 101-08 to treat previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). There were 12 complete responses and an estimated 24-month progression-free survival (PFS) rate of 93%. In the nine patients with deletion of chromosome 17 (del17p) or mutation in the tumor protein p53 (TP53; p53) gene, idelalisib plus rituximab produced three complete responses. Data are to be presented at the American Society of Clinical Oncology meeting in June.Based on the data, Gilead said it is evaluating Phase III trial designs for idelalisib as part of a first-line treatment regimen for CLL. The small molecule inhibitor of phosphoinositide 3-kinase (PI3K) delta is in three Phase III trials for previously treated CLL and a pair of Phase III trials for previously treated indolent non-Hodgkin's lymphoma (NHL). Gilead gained idelalisib through its 2011 acquisition of Calistoga Pharmaceuticals Inc. Gilead was off $1.40 to $54.96 on Thursday. Infinity Pharmaceuticals Inc. (NASDAQ:INFI) was off $7.12 (23%) to $24.32 on Thursday. The company's IPI-145 is an oral inhibitor of PI3K delta and gamma in Phase I testing to treat advanced hematologic malignancies. Biogen Idec Inc. (NASDAQ:BIIB) and Genentech Inc., a unit of Roche (SIX:ROG; OTCQX:RHHBY), co-market rituximab as Rituxan in the U.S., while Roche markets it as MabThera elsewhere.

Takeda reports Phase III data for diabetes compound

Thu, 16 May 2013 00:00:00 -0700

Takeda Pharmaceutical Co. Ltd. (Tokyo:4502) said once-daily 25 and 50 mg oral fasiglifam each met the primary endpoint of reducing HbA1c from baseline to week 24 vs. placebo in the Phase III CCT-003 trial to treat Type II diabetes. Compared to placebo, low-dose fasiglifam reduced HbA1c from baseline to week 24 by 0.75% and high-dose fasiglifam reduced the endpoint by 1.01%. The double-blind, Japanese trial enrolled 192 Type II diabetics who had inadequate glycemic control with diet and exercise. Data were presented at the Japan Diabetes Society meeting in Kumamoto. Takeda could not be reached for next steps. Fasiglifam is a free fatty acid receptor 1 (FFAR1; GPR40) agonist.

Oncothyreon off after Phase II data for PX-866

Thu, 16 May 2013 00:00:00 -0700

Oncothyreon Inc. (NASDAQ:ONTY) fell $0.64 (25%) to $1.97 on Thursday after reporting data from two Phase II trials of once-daily oral PX-866 to treat recurrent glioblastoma multiforme (GBM) and recurrent or metastatic castration-resistant prostate cancer (CRPC). In 33 evaluable patients with GBM at first recurrence after chemoradiation and adjuvant temozolomide, PX-866 missed the primary endpoint of objective response rate (ORR). The six-month progression-free survival (PFS) rate in the open-label trial was 17%. In the second trial, PX-866 in a six-week cycle missed the primary endpoint of lack of disease progression at week 12 in 43 patients with recurrent or metastatic CRPC not previously treated with docetaxel. The National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG) sponsored both trials. Data are to be presented at the American Society of Clinical Oncology meeting in June. PX-866, an oral phosphoinositide 3-kinase (PI3K) inhibitor, is also in Phase I/II testing to treat melanoma and colorectal cancer. Oncothyreon said it does not plan to move forward with development of PX-866 for GBM. Merck & Co. Inc. (NYSE:MRK) markets Temodar temozolomide. Sanofi (Euronext:SAN; NYSE:SNY) markets Taxotere docetaxel.

Halozyme gains on Phase I pancreatic cancer data

Thu, 16 May 2013 00:00:00 -0700

Halozyme Therapeutics Inc. (NASDAQ:HALO) gained $1.24 (18%) to $7.98 on Thursday after reporting data from 24 evaluable patients in the open-label, dose-escalation Phase Ib portion of a Phase I/II trial to treat previously untreated metastatic pancreatic cancer. Specifically, 1.6 and 3 ug/kg doses of IV PEGPH20 plus gemcitabine led to an overall response rate (ORR) of 42%. Data are slated to be presented at the American Society of Clinical Oncology meeting in June. PEGPH20 is a recombinant human PH20 hyaluronidase enzyme conjugated to polyethylene glycol (PEG).

Helsinn reports Phase III CINV data

Thu, 16 May 2013 00:00:00 -0700

Helsinn Healthcare S.A. (Pazzallo-Lugano, Switzerland) said a single dose of its oral Netu-palo-FDC (NEPA) plus dexamethasone was superior to a single dose of oral palonosetron plus dexamethasone on the primary endpoint in a Phase III trial to prevent chemotherapy-induced nausea and vomiting (CINV). The primary endpoint of the 1,455-patient NETU-08-18 study was improving complete response rate defined as no emesis and no use of rescue medication 25-120 hours after receiving chemotherapy. Data will be presented at the American Society of Clinical Oncology meeting in June. Helsinn said it plans to submit an NDA to FDA and MAA to EMA for NEPA to prevent acute and delayed CINV following both highly and moderately emetogenic chemotherapy. The product is a fixed-dose combination of 300 mg netupitant, a neurokinin 1 (NK1) Substance P receptor antagonist, and 0.5 mg palonosetron, a selective serotonin (5-HT3) receptor antagonist. Palonosetron is marketed to prevent CINV under the names Aloxi, Paloxi and Onicit in more than 60 countries worldwide. Eisai Co. Ltd. (Tokyo:4523; Osaka:4523) and Helsinn co-promote Aloxi in the U.S. Eisai has an exclusive, U.S. license to co-promote NEPA to prevent CINV in patients with cancer. IS Pharma plc (LSE:ISPH) has U.K. and Irish rights to the product, while Taiho Pharmaceutical Co. Ltd. has Japanese rights. Taiho is a subsidiary of Otsuka Holdings Co. Ltd. (Tokyo:4578).

Ambit raises $65 million in IPO

Thu, 16 May 2013 00:00:00 -0700

Ambit Biosciences Corp. (NASDAQ:AMBI) was off $0.61 to $7.39 in its first day of trading on Thursday after the company raised $65 million through the sale of 8.1 million shares at $8 in an IPO. Citigroup; Leerink; BMO Capital Markets; and Baird are underwriters. The price values the company at $141.7 million. Ambit proposed to raise up to $57.5 million in the IPO in February. In early 2014, Ambit plans to start a Phase III trial of quizartinib to treat relapsed or refractory acute myelogenous leukemia (AML) in patients with a genetic mutation in FMS-like tyrosine kinase 3 (FLT3; CD135). In March, Astellas Pharma Inc. (Tokyo:4503) terminated, effective Sept. 3, a 2009 deal with Ambit to co-develop FLT3 inhibitors, including quizartinib, an oral, small molecule FLT3 inhibitor (see BioCentury Extra, March 12).

Cyclacel, Stemline raise combined $80M in follow-ons

Thu, 16 May 2013 00:00:00 -0700

Cancer companies Stemline Therapeutics Inc. (NASDAQ:STML) and Cyclacel Pharmaceuticals Inc. (NASDAQ:CYCC) raised a combined $80 million in follow-ons on Thursday. Stemline raised $60 million in a bumped-up offering through the sale of 4.1 million shares at $14.50. Jefferies; Aegis; and Roth Capital Partners are underwriters. Stemline proposed the offering late May 6, when its share price was $14.96.Stemline is planning Phase IIb trials for SL-401 to treat blastic plasmacytoid dendritic cell neoplasm and third-line acute myelogenous leukemia (AML); and for SL-701 to treat newly diagnosed brainstem glioma and second-line glioblastoma multiforme (GBM). SL-401 is an IL-3 receptor targeting agent, and SL-701 is a cancer vaccine comprised of synthetic peptides administered via subcutaneous injection. Cyclacel raised $20 million through the sale of 6.7 million shares at $3. JMP Securities and Janney Montgomery Scott are underwriters. Cyclacel proposed the offering late Wednesday, when its share price was $3.47. Cyclacel's sapacitabine is in Phase III testing for AML. The company has rights to the cell cycle modulating nucleoside analog from Daiichi Sankyo Co. Ltd. (Tokyo:4568; Osaka:4568).Cyclacel was off $0.47 (14%) to $3 on Thursday, while Stemline was down $0.25 to $15. Both companies announced the news after market close on Thursday.

Vivus raises $220M in note offering

Thu, 16 May 2013 00:00:00 -0700

Vivus Inc. (NASDAQ:VVUS) raised $220 million through the sale of 4.5% unsecured senior convertible notes due May 1, 2020. The notes initially convert at $14.86, which is a 9% premium to Vivus' close of $13.59 on Tuesday, before the company proposed to raise $200 million in the offering. Vivus markets obesity drug Qsymia phentermine/topiramate in the U.S. Last week, Vivus disclosed in a conference call to discuss its 1Q13 earnings that it began discussions with large pharmas on how to "maximiz[e] the value" of the low-dose combination of phentermine and topiramate. Vivus launched Qsymia in the U.S. in September, but sales have disappointed (see BioCentury Extra, May 8). Vivus was off $0.37 to $12.54 on Thursday.

PTC files for IPO

Thu, 16 May 2013 00:00:00 -0700

PTC Therapeutics Inc. (South Plainfield, N.J.) filed to raise up to $85 million in an IPO underwritten by JPMorgan; Credit Suisse; Cowen; and Wedbush. PTC, which raised $60 million in a venture round in March, pulled its initial IPO in 2007 (see BioCentury, March 18).Last December, EMA accepted for review an MAA from PTC seeking conditional approval of ataluren to treat nonsense mutation Duchenne muscular dystrophy (DMD). Last month, the company began a Phase III trial to evaluate the small molecule that facilitates complete translation of proteins containing nonsense mutations. PTC also plans to start a Phase III trial next half to evaluate ataluren to treat nonsense mutation cystic fibrosis (CF).

Merck KGaA expands venture fund to EUR 100 million

Thu, 16 May 2013 00:00:00 -0700

Merck KGaA (Xetra:MRK) expanded to EUR 100 million ($129.7 million) its MS Ventures fund. The strategic fund was formed in 2009 with EUR 40 million ($51.9 million) to invest in biotech startups working in areas including cancer, neurodegenerative, immunology, fertility and endocrinology indications.

G-BA says Adcetris has 'unquantifiable' additional benefit

Thu, 16 May 2013 00:00:00 -0700

Germany's Federal Joint Committee (G-BA) said in a final assessment that lymphoma drug Adcetris brentuximab vedotin from Takeda Pharmaceutical Co. Ltd. (Tokyo:4502) has an "unquantifiable" degree of additional benefit. Adcetris has conditional approval from the European Commission to treat relapsed or refractory systemic anaplastic large cell lymphoma (ALCL) and for relapsed or refractory CD30-positive Hodgkin's lymphoma. Takeda will now negotiate a price for the Orphan drug with Germany's Statutory Health Insurance Funds Association (GKV-Spitzenverband). Under drug pricing law AMNOG, the additional benefit of Orphan products is regarded as having been demonstrated by the marketing authorization. Orphan products with an annual cost of less than EUR 50 million to the German statutory health insurance funds (GKV) do not undergo a formal benefit assessment through the Institute for Quality and Efficiency in Health Care (IQWiG), though G-BA still determines the extent of the additional benefit based on a product's marketing authorization studies. In a March assessment of Adcetris' cost, IQWiG said the Orphan drug would cost GKV about EUR 6.1-EUR 53.4 million ($7.9-$69.3 million) per year. If Adcetris' cost crosses the EUR 50 million threshold, Takeda will have to submit a full dossier to G-BA demonstrating Adcetris' benefit over a comparator despite the product's status as an Orphan drug (see BioCentury Extra, March 1). Seattle Genetics Inc. (NASDAQ:SGEN) is co-developing worldwide the antibody-drug conjugate (ADC) composed of an anti-CD30 mAb and monomethyl auristatin E (MMAE) with Takeda's Millennium Pharmaceuticals Inc. subsidiary. Seattle Genetics was down $1.39 to $36.32 on Thursday.

Roche, QB3 partner to launch startups

Thu, 16 May 2013 00:00:00 -0700

Roche (SIX:ROG; OTCQX:RHHBY) partnered with the California Institute for Quantitative Biosciences (QB3) to launch the Collaborative Startups program to identify, fund and support early life science startups in the San Francisco Bay Area. QB3 will identify candidates for the program from its incubator network; the QB3 Startup-in-a-Box program, which provides legal support to incorporate and structure new companies; QB3's annual Bridging the Gap award program, which provided $250,000 over two years for proof-of-concept research; or directly from university laboratories. Mission Bay, which funds QB3 startups, will provide $200,000-$500,000 in seed funding, and Roche will provide matching funds. Roche and Mission Bay Capital, both of whom may also invest in series A rounds for potential startups, plan to launch a couple companies a year. The pharma may also provide scientific expertise or resources to startups. QB3 is a collaboration of the University of California, San Francisco; UC Berkeley and UC Santa Cruz. On Wednesday, QB3 partnered with the Bayer Healthcare LLC subsidiary of Bayer AG (Xetra:BAYN) under a three-year deal to evaluate and support life science startups from QB3 (see BioCentury Extra, May 16).

IBM, UCB in big data deal for epilepsy

Thu, 16 May 2013 00:00:00 -0700

IBM Corp. (NYSE:IBM) and UCB Group (Euronext:UCB) partnered to develop a point-of-care analytics system to predict the probability of success of epilepsy treatments to inform treatment decisions. The partners said they completed proof of concept (POC) of a system in which they used data from anonymous patient records from IMS Health for 1.5 million U.S. epilepsy patients along with an "analytics machine approach" to model and predict outcomes of epilepsy treatments. UCB said the partners plan to publish the POC data and look for external stakeholders for collaborations to develop a point-of-care system, but declined to disclose details. The company declined to disclose details on who would own rights to any resulting system.On Thursday, UCB was down EUR 0.40 to EUR 44.99.

Evotec, Harvard in antibacterials deal

Thu, 16 May 2013 00:00:00 -0700

Evotec AG (Xetra:EVT) and Harvard University partnered to discover and develop small molecule inhibitors of peptidoglycan biosynthesis. Harvard will contribute research on proprietary assays, chemical starting points and x-ray crystallographic tools. Evotec, which will have rights to the antibacterials resulting from the deal, was up EUR 0.04 to EUR 2.82 on Thursday.

Aegerion gains on Juxtapid update

Thu, 16 May 2013 00:00:00 -0700

Aegerion Pharmaceuticals Inc. (NASDAQ:AEGR) jumped $14.73 (31%) to $61.70 on Thursday after the company said late Wednesday that the "launch metrics" for Juxtapid lomitapide are ahead of the company's internal plan and announced a price increase for the lowest doses of the homozygous familial hypercholesterolemia (hoFH) drug. At the Bank of America Merrill Lynch Healthcare Conference, Aegerion CEO Marc Beer said the company now estimates a $1 billion global market opportunity for the drug, assuming 4,000-5,000 patients on Juxtapid worldwide. Beer also said that, effective June 1, the annual price of Juxtapid will be $295,000 per patient, regardless of dose. Currently, the 5 and 10 mg doses of Juxtapid cost $235,000 and the 20, 40 and 60 mg doses cost $295,000 per patient. FDA approved Juxtapid in December. The stock move translated to a $425 million gain in market cap for a closing valuation of $1.8 billion.

FDA to discuss QRxPharma's MoxDuo

Thu, 16 May 2013 00:00:00 -0700

FDA's Anesthetic and Analgesic Drug Products Advisory Committee will meet on July 17 to discuss an NDA from QRxPharma Ltd. (ASX:QRX; OTCQX:QRXPY) for MoxDuo IR morphine/oxycodone to treat moderate to severe acute pain. The PDUFA date is Aug. 26. Last June, the agency issued a complete response letter requesting clarity on the safety and effectiveness of the immediate-release combination of oxycodone and morphine (see BioCentury Extra, June 28, 2012). QRxPharma was unchanged at A$1.13 on Thursday. In the U.S., the company was up $0.29 to $6.15.

Intra-Cellular appoints Rawlins to board

Thu, 16 May 2013 00:00:00 -0700

Neurology company Intra-Cellular Therapies Inc. (New York, N.Y.) appointed Sir Michael Rawlins, former chairman of the U.K.'s NICE, as a director. Rawlins' term ended on March 31, 2013; he had been chairman since the agency was established in 1999. Intra-Cellular's ITI-007, a dual serotonin (5-HT2A) receptor antagonist and dopamine receptor phosphoprotein modulator (DPPM), is in Phase II testing to treat schizophrenia.

House passes bill with JOBS deadline

Thu, 16 May 2013 00:00:00 -0700

The U.S. House of Representatives voted 416-6 to pass a bill, H. R. 701, that gives the U.S. Securities and Exchange Commission an Oct. 31 deadline to complete rulemaking on the reforms under the Jumpstart Our Business Startups Act (JOBS) to the Regulation A exemption. JOBS, which was signed into law last April, raised the offering size for the Regulation A exemption -- an SEC rule that enables companies to raise money on the public markets without doing a full blown IPO -- to $50 million from $5 million (see BioCentury, April 16, 2012).

Roche submits obinutuzumab applications