The Daily Extra

SCOTUS: pay-for-delay subject to antitrust litigation

Mon, 17 Jun 2013 17:38:32 -0700

The U.S. Supreme Court ruled on Monday in Federal Trade Commission v. Actavis Inc., et al. that pay-for-delay settlements between branded and generic drug manufacturers are not immune from antitrust litigation. The decision overturns a ruling by the U.S. Court of Appeals for the Eleventh Circuit that a pay-for-delay deal between the pharmaceuticals business of Solvay S.A. (Euronext:SOLB) and generic drug manufacturers, including Actavis Inc. (NYSE:ACT; formerly Watson Pharmaceuticals Inc.), was "immune from antitrust attack."

The appeals court had affirmed a district court's dismissal of the suit by the Federal Trade Commission against Solvay, which had paid generic manufacturers to abandon patent challenges and refrain from marketing a generic version of testosterone replacement therapy AndroGel. The U.S. District Court for the Northern District of Georgia dismissed the case because "the FTC had not alleged that the challenged agreements excluded competition to a greater extent than would the patent."

In a 5-3 decision, the Supreme Court held the "FTC should have been given the opportunity to prove its antitrust claim," as the anticompetitive consequences of pay-for-delay deals will "at least sometimes prove unjustified." The Supreme Court, which remanded the case back to the district court, did reject FTC's argument that pay-for-delay deals should be considered "presumptively unlawful," which would have put the burden of proof on the branded company to show the deals are not anticompetitive and unlawful.

AbbVie Inc. (NYSE:ABBV), which acquired the pharmaceuticals business of Solvay in 2010, recorded AndroGel sales of $1.2 billion in 2012.

J&J acquiring Aragon for androgen receptor antagonist program

Mon, 17 Jun 2013 17:38:32 -0700

Johnson & Johnson (NYSE:JNJ) will acquire cancer company Aragon Pharmaceuticals Inc. (San Diego, Calif.) for $650 million in cash up front, plus up to $350 million in milestones. J&J will gain Aragon's androgen receptor antagonist program, which includes ARN-509, a second-generation androgen receptor antagonist in Phase II testing to treat castration-resistant prostate cancer (CRPC). Prior to the deal, Aragon will spin out into Seragon Pharmaceuticals all of its assets outside of the androgen receptor antagonist program. The newco -- which will be financed by existing Aragon investors and will retain Aragon's management team -- will focus on Aragon's selective estrogen receptor degrader (SERD) platform, including ARN-810, an oral SERD in Phase I testing for estrogen receptor-positive metastatic breast cancer.

J&J said ARN-509 will complement Zytiga abiraterone acetate, which the pharma markets in the U.S. and EU in combination with prednisone to treat metastatic CRPC. The deal, which has been approved by the boards of both companies, is slated to close next quarter. BofA Merrill Lynch advised Aragon.

Medivation Inc. (NASDAQ:MDVN) fell $3.45 to $47.41 on Monday on news of the deal. The company and partner Astellas Pharma Inc. (Tokyo:4503) market prostate cancer drug Xtandi enzalutamide, an oral androgen receptor antagonist. Medivation is appealing a December ruling by a California state court that Aragon owns ARN-509, which Medivation has said is based on technology similar to Xtandi (see BioCentury Extra, Dec. 26, 2012).

MedImmune, NGM in metabolic deal

Mon, 17 Jun 2013 17:38:32 -0700

MedImmune LLC partnered with NGM Biopharmaceuticals Inc. (South San Francisco, Calif.) to develop and commercialize peptide and antibody therapeutics to treat Type II diabetes and obesity based on a set of undisclosed secreted peptide hormones identified with NGM's enteroendocrine cell (EEC) program. The companies will characterize and prioritize the peptide hormones and will jointly develop candidates, to which MedImmune has an exclusive option to license worldwide rights. MedImmune, the biologics unit of AstraZeneca plc (LSE:AZN; NYSE:AZN), will be responsible for further preclinical and clinical development and commercialization of licensed candidates. NGM will receive an undisclosed upfront payment and research funding. The company also is eligible for undisclosed milestones, plus royalties.

Amicus falls on delay for Fabry's compound

Mon, 17 Jun 2013 17:38:32 -0700

Amicus Therapeutics Inc. (NASDAQ:FOLD) fell $0.65 (20%) to $2.54 on Monday after announcing that FDA said 12-month data from a Phase III trial of Amigal migalastat to treat Fabry's disease would not support approval of an NDA. The news came at a meeting Amicus had with the agency to discuss six-month data from the Phase III FACETS (Study 011) trial of Amigal. In February, Amicus had said the 12-month data, which are expected in 4Q13, would "add to the entirety of the data that FDA has indicated would support a potential U.S. conditional approval." Amicus reported six-month data from FACETS in December showing that Amigal missed the primary endpoint (see BioCentury Extra, Feb. 15).

Amicus said it now plans to meet with FDA in 2H14 to discuss a potential U.S. approval pathway for Amigal. The company also expects to report top-line data from the Phase III ATTRACT (Study 012) trial evaluating Amigal vs. enzyme replacement therapy (ERT) for Fabry's in 2H14.

Amicus is partnered with GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) for Amigal, a small molecule that enhances alpha galactosidase A activity, under an amended 2010 deal. At March 31, Amicus had $84.8 million in cash, which it said was sufficient to fund the company until 2H14.

IQWiG again rebuffs Caprelsa

Mon, 17 Jun 2013 17:38:32 -0700

Germany's Institute for Quality and Efficiency in Healthcare (IQWiG) said thyroid cancer drug Caprelsa vandetanib from AstraZeneca plc (LSE:AZN; NYSE:AZN) provides "no additional benefit" over best supportive care, the comparator requested by Germany's Federal Joint Committee (G-BA). IQWiG said in a reassessment that AstraZeneca did not account for a difference in treatment duration between Caprelsa and the comparator, leading to "uncertainty" in the adverse event data. As a result, IQWiG said it "cannot be ruled out" that negative effects of Caprelsa outweigh its benefits to treat aggressive, symptomatic medullary thyroid cancer (MTC) that is unresectable and locally advanced or metastatic -- the drug's approved indication. According to IQWiG's assessment, the European Commission approved Caprelsa for a limited population to establish a positive benefit/risk profile.

AstraZeneca has until July 8 to respond to the assessment; a final assessment from G-BA is expected in early September.

Last September, G-BA issued an unfavorable benefit assessment for Caprelsa because AstraZeneca provided data from a broader patient population than the one for which the EGFR and VEGF receptor kinase inhibitor is approved. AstraZeneca took advantage of temporary changes to G-BA's assessment process allowing companies to immediately resubmit dossiers for drugs that were given a "no additional benefit" rating because data were deemed incomplete (see BioCentury Extra, Sept. 6, 2012).

IQWiG rebuffs Lyxumia for Type II diabetes

Mon, 17 Jun 2013 17:38:32 -0700

Germany's Institute for Quality and Efficiency in Healthcare (IQWiG) said Lyxumia lixisenatide from Sanofi (Euronext:SAN; NYSE:SNY) has "no additional benefit" over comparators requested by Germany's Federal Joint Committee (G-BA). Sanofi did not submit data directly comparing the glucagon-like peptide-1 receptor (GLP-1R) agonist to comparators. The institute said data submitted by the company indirectly comparing Lyxumia with two of the requested comparators -- in combination with metformin vs. sulfonylurea plus metformin, and in combination with basal insulin vs. human insulin -- were not "suitable."

Sanofi did not submit data indirectly comparing Lyxumia in combination with sulfonylurea vs. sulfonylurea plus metformin, another comparator requested by G-BA. Additionally, IQWiG rejected data submitted by Sanofi indirectly comparing Lyxumia plus metformin and sulfonylurea vs. basal insulin plus metformin and sulfonylurea because G-BA had requested Sanofi compare Lyxumia plus metformin and sulfonylurea vs. metformin and human insulin.

Sanofi has until July 8 to respond to the assessment; a final assessment from G-BA is expected in early September. The pharma has global commercialization rights to Lyxumia, which is under FDA review with an undisclosed PDUFA date, from Zealand Pharma A/S (CSE:ZEAL) under a 2003 deal. Zealand was up DKK1.50 to DKK68.50 on Monday.

Elan shareholders approve buy back, Royalty bid lapses

Mon, 17 Jun 2013 17:38:32 -0700

A bid from Royalty Pharma (New York, N.Y.) to acquire Elan Corp. plc (NYSE:ELN) lapsed after Elan shareholders approved the biotech's proposal to repurchase $200 million in shares. Royalty was seeking to acquire Elan for $13 per share in cash plus a contingent value right (CVR) worth up to $2.50, which would have valued Elan at up to $7.9 billion. The bid was contingent on Elan shareholders rejecting all four transactions including the share buyback that Elan has proposed since Royalty's offer was unveiled in February.

Royalty had been seeking to make its offer contingent on Elan shareholders rejecting only two of the proposals: the acquisition of rare disease company AOP Orphan Pharmaceuticals AG (Vienna, Austria); and Elan's proposal to pay Theravance Inc. (NASDAQ:THRX) $1 billion for a 21% interest in royalties Theravance is eligible to receive from partner GlaxoSmithKline plc (NSE:GSK; NYSE:GSK) for four respiratory programs. The Irish Takeover Panel denied Royalty's request, but Royalty said the Irish High Court is scheduled to hear proceedings on Wednesday for a judicial review of the takeover panel's decision.

On Friday, Elan said it was proceeding with a formal sale process. The company was off $0.17 to $13.49 on Monday (see BioCentury Extra, June 14).

Newco XO1 debuts with $11M from Index

Mon, 17 Jun 2013 17:38:32 -0700

Index Ventures launched XO1 Ltd. (Cambridge, U.K.) with $11 million in a series A round to develop ichorcumab, a preclinical synthetic mAb against the exosite 1 region of thrombin licensed from the University of Cambridge. The virtual newco plans to start clinical testing of the anticoagulant in volunteers within two years. Index's David Grainger is interim CEO and the firm's Kevin Johnson joined XO1's board. Andy Walsh from Cambridge Enterprise, the university's commercialization arm, also joined XO1's board.

The investment came from Index's EUR 150 million ($197.2 million) Index Life VI, the firm's first fund solely dedicated to life sciences (see BioCentury, March 26, 2012).

Onconova files for IPO

Mon, 17 Jun 2013 17:38:32 -0700

Cancer company Onconova Therapeutics Inc. (Newton, Pa.) filed to raise up to $75 million in an IPO underwritten by Citigroup; Leerink; Piper Jaffray; and Janney Montgomery Scott. Onconova's rigosertib is in the Phase III ONTIME trial to treat high-risk myelodysplastic syndromes (MDS). Top-line overall survival (OS) data from the trial, for which Onconova has an SPA, are expected in 4Q13 or 1Q14. The oral dual inhibitor of phosphoinositide 3-kinase (PI3K) and polo-like kinase 1 (PLK1; STPK13) also is in the Phase III ONTRACT trial to treat metastatic pancreatic cancer and in Phase II testing to treat lower-risk MDS and head and neck cancers. Baxter International Inc. (NYSE:BAX) has exclusive European commercialization rights to rigosertib, and SymBio Pharmaceuticals Ltd. (JASDAQ:4582) has rights to develop and commercialize the compound in Japan and Korea.

Repros, Exact Sciences planning follow-ons

Mon, 17 Jun 2013 17:38:32 -0700

Repros Therapeutics Inc. (NASDAQ:RPRX) and Exact Sciences Corp. (NASDAQ:EXAS) both announced plans late Monday to raise money in follow-ons. Repros proposed to sell up to 3 million shares in a follow-on underwritten by BofA Merrill Lynch; Lazard; Ladenburg; and Ascendiant Capital Markets. If sold at Repros' close of $17.93 on Monday, the company would raise $53.8 million. Repros' Androxal enclomiphene, a trans-isomer of clomiphene citrate, is in Phase III testing to treat secondary hypogonadism, with an NDA submission slated for mid-2014.

Separately, Exact Sciences proposed a follow-on underwritten by Jefferies and Baird. Last week, Exact Sciences said it submitted the final module of a PMA to FDA for Cologuard as a colorectal cancer screening test. Cologuard is a non-invasive stool DNA test that uses a multiplexed quantitative Invader assay for the simultaneous detection of methylated and unmethylated sequences in the promoter region of the vimentin (VIM) gene (see BioCentury Extra, June 10).

Repros was off $0.81 on Monday. Exact Sciences was up $0.25 to $12.59 on the day.

RaQualia looks to raise at least $35 million

Mon, 17 Jun 2013 17:38:32 -0700

Gastrointestinal company RaQualia Pharma Inc. (JASDAQ:4579) said it hopes to raise at least Y3.3 billion ($34.7 million) through the exercise of 2,500 stock acquisition rights by Merrill Lynch Japan Securities. Each right entitles Merrill to purchase 1,000 shares at 90% of the previous day's closing price, with an initial exercise price of Y1,310, RaQualia's closing price on Friday, before the deal was announced. The minimum exercise price is Y917. RaQualia was up Y201 (15%) to Y1,511 on Monday.

Last year, RaQualia said it was restructuring to focus on four compounds in development for gastrointestinal diseases, including RQ-00000010, a serotonin 5-HT4 partial agonist in Phase I testing, and RQ-00000004, a H+/K ATPase pump in Phase II testing to treat gastroesophageal reflux disease (GERD) (see BioCentury Extra, Nov. 13, 2012).

NICE to help develop HTA program in India

Mon, 17 Jun 2013 17:38:32 -0700

India is in the process of developing a health technology assessment board and the country's Department of Health Research signed a memorandum of understanding (MOU) with the U.K.'s NICE to help with the process. NICE will provide advice and support on clinical practice guidelines and quality standards, and how to apply and implement health technology assessments. The parties are setting up a joint steering committee.

Gilead reports interim ORR data for idelalisib

Mon, 17 Jun 2013 17:38:32 -0700

Gilead Sciences Inc. (NASDAQ:GILD) reported interim data showing twice-daily oral idelalisib led to an overall response rate (ORR), the primary endpoint, of 53.6% in the Phase II Study 101-09 to treat refractory indolent non-Hodgkin's lymphoma (NHL). In 125 patients in the single-arm, open-label trial, there were five complete responses, 60 partial responses and two minor responses, plus 46 cases of stable disease. The median progression-free survival (PFS) was 11.4 months, and 89% of patients experienced "some shrinkage" in lymph node size. Data are slated to be presented on Thursday at the Malignant Lymphoma meeting in Lugano.

Idelalisib is in Phase III testing in combination with various approved therapies for previously treated indolent NHL and for previously treated chronic lymphocytic leukemia (CLL). Gilead gained idelalisib, a small molecule inhibitor of phosphoinositide 3-kinase (PI3K) delta, through its 2011 acquisition of Calistoga Pharmaceuticals Inc. Gilead was off $1.20 to $51.03 on Monday.

Cempra raises $50.8 million in follow-on

Fri, 14 Jun 2013 00:00:00 -0700

Cempra Inc. (NASDAQ:CEMP) raised $50.8 million through the sale of 7.3 million shares at $7 in a follow-on underwritten by Barclays; Stifel Nicolaus Weisel; Cowen; Needham; and SunTrust. Cempra proposed the follow-on late Thursday, when its stock price was $8.13. On Friday, the company was down $1.13 (14%) to $7 (see BioCentury Extra, June 13).In 4Q13, Cempra plans to start a Phase III trial of lead product solithromycin to treat community-acquired bacterial pneumonia (CABP). The trial will compare IV solithromycin with IV moxifloxacin in about 800 patients who will then be switched to oral formulations of the antibiotics. The oral formulation of solithromycin is already in a Phase III trial for CABP. Cempra has exclusive rights to the fluoroketolide/macrolide antibiotic from Optimer Pharmaceuticals Inc. (NASDAQ:OPTR) outside countries in the Association of Southeast Asian Nations (ASEAN).

Elan authorizes formal sale process

Fri, 14 Jun 2013 00:00:00 -0700

Elan Corp. plc (NYSE:ELN) said it is proceeding with a formal sale process "in light of the expressions of interest received to date," while suitor Royalty Pharma (New York, N.Y.) called the move a "frustrating tactic" intended to thwart its bid to acquire the biotech. Royalty is seeking to acquire Elan for $13 per share in cash plus a contingent value right (CVR) worth up to $2.50, which would value Elan at up to $7.9 billion. Royalty's bid is contingent upon Elan shareholders voting down four transactions that the biotech has proposed since Royalty's offer was unveiled in February. Votes are due by Monday. Royalty said that a preliminary count of the 81% of votes received as of Thursday indicates Elan shareholders are poised to reject three of the transactions, including a proposal to pay Theravance Inc. (NASDAQ:THRX) $1 billion for a 21% interest in royalties Theravance is eligible to receive from partner GlaxoSmithKline plc (NSE:GSK; NYSE:GSK) for four respiratory programs. Royalty said a narrow majority of votes have been cast in favor of Elan's proposal to repurchase $200 million in shares. Additionally, Elan's former partner Johnson & Johnson (NYSE:JNJ) disclosed in an SEC filing late Thursday that it sold its remaining stake in Elan, or 25.4 million Elan ADSs valued at about $320.1 million based on Elan's close of $12.61 on Thursday. J&J, which had been Elan's largest shareholder with an 18% stake, first sold a 13.1% stake of its shares in April (see BioCentury, April 22).Elan was up $1.05 to $13.66 on Friday. Theravance was up $0.66 to $36.04.

Woodcock says FDA 'actively investigating' antidiabetics

Fri, 14 Jun 2013 00:00:00 -0700

FDA is actively investigating concerns that glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors -- collectively known as incretin mimetics -- could cause pancreatitis, Janet Woodcock, director of FDA's Center for Drug Evaluation and Research, told BioCentury. Responding to a question about the agency's response to concerns about the class of diabetes drugs, Woodcock told BioCentury This Week television that FDA "has been aware of this, and certainly we're doing more investigations." She added that "these are the types of things that need to be resolved as quickly as possible." The agency is considering requiring additional sponsor studies or an FDA observational study to evaluate the potential pancreatic toxicity of the class, according to Solomon Iyasu, director of CDER's Office of Surveillance and Epidemiology. In a presentation on Thursday at the Pancreatitis-Diabetes-Pancreatic Cancer Workshop, Iyasu noted the limitations in data from both FDA's Adverse Event Reporting System (AERS) and current FDA-required observational studies. He said "adequately powered, long-term epidemiological studies" will be necessary to assess concerns about the class of diabetes drugs. Iyasu also said the agency is requiring that cases of pancreatitis and pancreatic cancer be reported as adverse events of special interest in large cardiovascular outcome trials for GLP-1 therapies. Additionally, the agency is reviewing the results of a post-marketing epidemiological study of pancreatic cancer risk with GLP-1 analog Byetta exenatide from Bristol-Myers Squibb Co. (NYSE:BMY). The workshop was sponsored by NIH's National Cancer Institute and National Institute of Diabetes and Digestive and Kidney Diseases.Earlier this week, the British Medical Journal published a report that says companies have not done "critical safety studies" and that regulators have not requested such studies to address the concerns of pancreatitis and pancreatic cancer with insulin mimetics (see BioCentury Extra, June 11). The interview with Woodcock, including her comments on a joint meeting last week in which two advisory committees voted to loosen the REMS for diabetes drug Avandia rosiglitazone from GlaxoSmithKline plc (LSE:GSK; NYSE:GSK), will be broadcast in Washington at 8:30am on Sunday morning on WUSA channel 9, and will be posted at www.BioCenturytv.com at 9am (see BioCentury, June 10).

Draft bill would increase CBO's budget scoring window

Fri, 14 Jun 2013 00:00:00 -0700

A spokesperson said Rep. Michael Burgess (R-Texas) plans to introduce within the next few weeks a bill that would allow the Congressional Budget Office to expand the time period over which it calculates the budgetary cost of legislation. A discussion draft of the bill -- which would allow CBO under "certain circumstances" to score bills over a 30-year period instead of a 10-year period -- is circulating in Washington. The bill would allow CBO to include future savings from preventive health services and products when scoring bills. The spokesperson said CBO has considered savings for some preventative health services in previous models of scored bills, but because the office currently uses a 10-year period to score bills, the upfront costs tend to outweigh any potential long-term savings. If enacted, Burgess' bill could provide more favorable assessments by CBO of any legislation seeking to require Medicare coverage of obesity products, including Part D coverage of obesity drugs. Medicare does not currently cover obesity products. According to an April report released by the Campaign to End Obesity, an economic model that uses a 75-year period and includes weight-loss drugs under Medicare Part D could yield long-term savings of up to $11.4 billion. The not-for-profit said a 10-year scoring model "fails to capture the potential long-term budget impacts of preventive health strategies." Co-founder Stephanie Silverman said legislation that "increases the length of time that Congress can consider the economic costs and returns from any particular program is incredibly valuable for preventive care programs."

Reps. continue to work on exempting user fees from sequestration

Fri, 14 Jun 2013 00:00:00 -0700

Lawmakers on the House Appropriations Committee are continuing to work to exempt future FDA user fees from sequestration, but in the meantime the committee voted to send to the full U.S. House of Representatives a FY14 appropriations bill that would give FDA $4.3 billion in total funding. A spokesperson for Rep. Sam Farr (D-Calif.) said the Congressman agreed during a markup of that bill to withdraw an amendment that would have exempted future FDA user fees from sequestration at the request of committee Chair Robert Aderholt (R-Ala.). Farr is ranking minority member of the House Appropriations subcommittee with responsibility for FDA's budget. According to the spokesperson, Aderholt agreed to work separately on incorporating the measure in the version of the appropriations bill that will be sent to the full House; a full vote on the bill has not yet been scheduled. The appropriations bill sent to the House would increase base appropriations -- taxpayer funding -- for FDA funding by $24 million from the level enacted for FY13 through continuing resolutions, not including sequestration cuts. The bill would provide FDA with about $1.8 billion in user fees and $2.5 billion in base appropriations in FY14. The U.S. Senate Committee on Appropriations is scheduled to mark-up the Senate's FY14 appropriations bill for agriculture, rural development and FDA on June 20.

FDA publishes final guidance for combination treatments

Fri, 14 Jun 2013 00:00:00 -0700

FDA published final guidance on the co-development of two or more new investigational drugs. The final guidance reiterates language in 2010 draft guidance on how to choose and test combinations of investigational new drugs in the clinic and clarifies how INDs and marketing applications should be treated for combinations. FDA maintained co-development should be reserved for when there is a compelling biological rationale for the combination; an established biomarker that suggests the combination has substantial activity and greater additive activity, a more durable response or a better toxicity profile than the individual agents alone; the agents cannot be developed individually; and the combination seeks to treat a serious disease or condition (see BioCentury Extra, Dec. 14, 2010).

USPTO issues guidance to examiners following Myriad decision

Fri, 14 Jun 2013 00:00:00 -0700

The U.S. Patent and Trademark Office issued preliminary guidance to patent examiners instructing them to reject product claims "drawn solely to naturally occurring nucleic acids or fragments thereof, whether isolated or not." The move follows the ruling on Thursday by the U.S. Supreme Court in Association for Molecular Pathology, et al. v. U.S. PTO, et al. that isolated DNA cannot be patented but cDNA can be patented. The USPTO said it will continue to analyze the opinion and issue more comprehensive guidance on determining patent subject matter eligibility, including the role isolation plays in these determinations (see BioCentury Extra, June 13).

EMA holding workshop on parallel scientific advice

Fri, 14 Jun 2013 00:00:00 -0700

EMA will hold a workshop on Nov. 26 to discuss providing parallel scientific and regulatory advice with health-technology assessment (HTA) bodies in the drug development process. The workshop will examine an ongoing pilot project of parallel scientific advice process between EMA and HTAs, as well how to optimize the parallel scientific advice process and the development of best practices.

Retroscreen raises L25.5 million

Fri, 14 Jun 2013 00:00:00 -0700

Retroscreen Virology Group plc (LSE:RVG) raised L25.5 million ($39.6 million) through the sale of 12.8 million shares at 200p in a placing with existing and new institutional investors. The price is a 29% discount to Retroscreen's close of 280p on Thursday, before the offering was announced. Numis Securities was placement agent. Retroscreen conducts preclinical and clinical human viral challenge studies for companies developing antivirals and vaccines. The stock was off 37.50p (13%) to 242.50p on Friday.

Mast Therapeutics raises $25 million in follow-on

Fri, 14 Jun 2013 00:00:00 -0700

Mast Therapeutics Inc. (NYSE-M:MSTX) raised $25 million through the sale of 50 million units at $0.50 in a follow-on underwritten by Piper Jaffray and Canaccord. Each unit comprises a share and a five-year warrant to purchase 0.5 shares, with each whole warrant exercisable at $0.65. Mast's MST-188 is in the Phase III EPIC trial to treat sickle cell disease in pediatric patients, with a Phase II trial in acute limb ischemia slated to start by year end or early next year. MST-188 is an antithrombotic poloxamer that adheres to hydrophobic surfaces. Mast was down $0.20 (31%) to $0.44 on Friday.

Conatus files for IPO

Fri, 14 Jun 2013 00:00:00 -0700

Conatus Pharmaceuticals Inc. (San Diego, Calif.) proposed to raise up to $69 million in an IPO underwritten by Stifel Nicolaus Weisel; Piper Jaffray; JMP Securities; and SunTrust. In 2H13, Conatus plans to start a Phase IIb/III trial to evaluate emricasan (IDN-6556) to treat patients with liver fibrosis post orthotopic liver transplant due to HCV infection, and a Phase IIb trial to treat acute-on-chronic liver failure. The company also plans to start a Phase IIb trial to evaluate the pan-caspase inhibitor to treat chronic liver failure in 2H14. Conatus gained emricasan through its 2010 acquisition of the Idun Pharmaceuticals Inc. subsidiary of Pfizer Inc. (NYSE:PFE)(see BioCentury, Aug. 9, 2010).

Supreme Court strikes isolated DNA patents

Thu, 13 Jun 2013 00:00:00 -0700

The U.S. Supreme Court unanimously ruled on Thursday that isolated DNA cannot be patented but cDNA can be patented. The decision is consistent with recommendations submitted by the Department of Justice in the case, Association for Molecular Pathology, et al. v. U.S. PTO, et al. (see BioCentury, April 22). Both sides declared victory in the case, in which the American Civil Liberties Union litigated against claims in U.S. patents from Myriad Genetics Inc. (NASDAQ:MYGN) covering breast cancer 1 early onset (BRCA1) and BRCA2 tests. The ACLU said that as a result of the ruling, "patients will have greater access to genetic testing and scientists can engage in research on these genes without fear of being sued." At least two companies -- Ambry Genetics Corp. (Aliso Viejo, Calif.) and Gene By Gene Ltd. (Houston, Texas) -- announced on Thursday that they are offering BRCA1 and BRCA2 tests based on gene sequencing technology. Prior to Thursday's ruling, Gene By Gene had offered its test only to patients outside the U.S. Gregory Castanias, a partner at Jones Day who argued the case for Myriad, told BioCentury the ruling leaves Myriad's cDNA claims in place. More important, he said, the Supreme Court reinforced the patentability of method claims like Myriad's claims on the use of BRCA1 and BRCA2 as probes. Shares of Myriad were up more than 10% on Thursday before ultimately closing off $1.91 at $32.01.Jim Greenwood, president and CEO of the Biotechnology Industry Organization, released a statement calling the decision a "troubling departure from decades of judicial and Patent and Trademark Office precedent supporting the patentability of DNA molecules that mimic naturally-occurring sequences." He said the decision "could unnecessarily create business uncertainty for a broader range of biotechnology inventions."

Prism raises $15 million in series C

Thu, 13 Jun 2013 00:00:00 -0700

Prism Pharma Co. Ltd. (Yokohama, Japan) raised about $15 million in a series C round led by Innovation Network Corp. of Japan. Existing investor Development Bank of Japan also participated along with four other existing investors. Next half, Prism plans to start Phase I testing of PRI-724 to treat liver fibrosis induced by HCV, with data expected in early 2015. The company also plans to evaluate PRI-724 in additional undisclosed fibrosis indications in dermatology and ophthalmology. Eisai Co. Ltd. (Tokyo:4523; Osaka:4523) has rights to the beta-catenin (CTNNB1) inhibitor from Prism in cancer indications, for which the compound is in Phase I testing. Prism has raised about $35 million in venture funding since its inception in 2006.The Innovation Network debuted in 2009 with Y280 billion ($2.9 billion), including Y266 billion ($2.7 billion) from the Japanese government and Y14 billion ($144.2 million) from private companies.

NanoString sets IPO range

Thu, 13 Jun 2013 00:00:00 -0700

Diagnostics company NanoString Technologies Inc. (Seattle, Wash.) amended its IPO and now plans to sell 5.4 million shares at $13-$15. At the $14 midpoint, NanoString would raise $75.6 million and be valued at $204.3 million. The company filed to raise up to $86.3 million in the IPO in May. JPMorgan, Morgan Stanley, Leerink and Baird are underwriters. Earlier this year, NanoString launched its Prosigna Breast Cancer Prognostic Gene Signature Assay in the EU and Israel to subtype breast cancer tumors 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.).

Cempra planning follow-on

Thu, 13 Jun 2013 00:00:00 -0700

Cempra Inc. (NASDAQ:CEMP) proposed a follow-on late Thursday underwritten by Barclays; Stifel; and Cowen. Cempra also said it will start in 4Q13 a Phase III trial of lead product solithromycin to treat community-acquired bacterial pneumonia (CABP). The trial will compare IV solithromycin with IV moxifloxacin in about 800 patients who will then be switched to oral formulations of the antibiotics. The oral formulation of solithromycin is already in a Phase III trial for CABP. Cempra, which made both announcements after market close, was up $0.18 to $8.13 on Thursday.Last month, HHS's Biomedical Advanced Research and Development Authority (BARDA) awarded Cempra up to $58 million to develop solithromycin to treat infections in pediatric populations and infections caused by bioterror threat pathogens. Cempra has exclusive rights to the fluoroketolide/macrolide antibiotic from Optimer Pharmaceuticals Inc. (NASDAQ:OPTR) outside countries in the Association of Southeast Asian Nations (ASEAN) (see BioCentury Extra, May 28).

NICE now backs Iluvien for DME subset

Thu, 13 Jun 2013 00:00:00 -0700

The U.K.'s NICE issued draft guidance recommending the use of Iluvien fluocinolone acetonide intravitreal implant from Alimera Sciences Inc. (NASDAQ:ALIM) for a subset of patients with chronic diabetic macular edema (DME). The committee recommends use of Iluvien to treat DME considered insufficiently responsive to available therapies but only in patients who have had their natural lens replaced with an intraocular lens. The recommendation is contingent on Alimera providing Iluvien at an undisclosed discount under a patient access scheme. The guidance reverses final guidance issued in January, in which NICE recommended against the use of Iluvien for all insufficiently responsive DME patients. With the new discount, the committee said the most plausible incremental cost-effectiveness ratio (ICER) for Iluvien in the subgroup of patients with an intraocular lens would be L17,600-L30,300 ($27,328-$47,047) per quality-adjusted life year (QALY) gained. Iluvien is approved to treat chronic DME considered insufficiently responsive to available therapies in Austria, Portugal, the U.K., France and Germany. The injectable insert delivering sustained release fluocinolone acetonide (FA) to the retina is under review in the U.S., with an Oct. 17 PDUFA date. Alimera, which has rights to Iluvien from pSivida Corp. (NASDAQ:PSDV; ASX:PVA), was up $0.08 to $4.88 on Thursday. pSivida was down $0.10 to $3.37 on NASDAQ. In Australia, the stock was unchanged on the day at A$3.69.

Royalty says Elan bid may lapse

Thu, 13 Jun 2013 00:00:00 -0700

Royalty Pharma (New York, N.Y.) said its offer to acquire Elan Corp. plc (NYSE:ELN) may lapse based on preliminary voting results from Elan shareholders. Royalty is offering to buy Elan for $13 per share in cash plus a contingent value right (CVR) worth up to $2.50, valuing Elan at up to $7.9 billion. The offer is contingent on Elan shareholders rejecting four of Elan's proposed transactions at a June 17 meeting, but Royalty said that based on the votes as of Wednesday one of the transactions -- Elan's proposal to repurchase $200 million in shares under a new buyback program -- will be approved. Royalty is seeking permission from the Irish Takeover Panel to make its offer contingent on Elan shareholders rejecting only two of the deals: the acquisition of rare disease company AOP Orphan Pharmaceuticals AG (Vienna, Austria) for EUR 175.7 million ($231.8 million) in cash and EUR 78.8 million ($104 million) in Elan shares, and Elan's proposal to pay Theravance Inc. (NASDAQ:THRX) $1 billion for a 21% interest in royalties Theravance is eligible to receive from partner GlaxoSmithKline plc (NSE:GSK; NYSE:GSK) for four respiratory programs (see BioCentury, May 27). Elan's board unanimously rejected Royalty's offer earlier this week. On Thursday, the company was off $0.49 to $12.61 (see BioCentury Extra, June 10).

Boehringer reports SVR12 data for all-oral HCV regimen

Thu, 13 Jun 2013 00:00:00 -0700

Boehringer Ingelheim GmbH (Ingelheim, Germany) reported data from the Phase IIb SOUND-C3 trial evaluating an all-oral regimen that included the company's faldaprevir and deleobuvir to treat chronic HCV genotype 1 infection in treatment-naïve patients. In the open-label trial, 19 of 20 (95%) evaluable patients who received once-daily faldaprevir (BI 201335) plus twice-daily deleobuvir (BI 207127) and ribavirin for 16 weeks achieved a sustained virologic response (SVR) 12 weeks after the end of treatment, including all four patients with liver cirrhosis. Data were presented at the Asian Pacific Association for the Study of the Liver meeting in Singapore.Boehringer is evaluating the interferon-free regimen of faldaprevir in combination with deleobuvir and ribavirin in the Phase III HCVerso 1, HCVerso 2 and HCVerso 3 trials to treat HCV genotype 1b infection in treatment-naïve patients. Data are expected in 2Q14. Faldaprevir is an oral HCV NS3/4A protease inhibitor, and deleobuvir is an oral non-structural protein 5B (NS5B) RNA-dependent polymerase inhibitor.

Lilly stops AD trial of LY2886721

Thu, 13 Jun 2013 00:00:00 -0700

Eli Lilly and Co. (NYSE:LLY) discontinued the Phase II BACC trial evaluating once-daily oral LY2886721 for 26 weeks in patients with Alzheimer's disease (AD) after cases of abnormal liver biochemical tests were identified as part of routine monitoring. The double-blind, placebo-controlled, international trial was slated to enroll about 128 patients with mild cognitive impairment (MCI) due to AD or mild AD who test positive for amyloid plaque. Lilly, which will continue to monitor all patients with abnormal tests, said it does not believe the abnormal tests are related to LY2886721's mechanism of inhibiting beta secretase. The pharma said it will further evaluate the data before determining next steps for the development program of LY2886721, a beta secretase inhibitor.

Celltrion presents Phase I data for CT-P13

Thu, 13 Jun 2013 00:00:00 -0700

Celltrion Inc. (KOSDAQ:068270) presented Phase I data comparing its CT-P13 with Remicade infliximab from Johnson & Johnson (NYSE:JNJ) and partner Merck & Co. Inc. (NYSE:MRK) at the European League Against Rheumatism meeting on Thursday. In 250 patients with active ankylosing spondylitis in the Phase I PLANETAS trial, CT-P13 and Remicade had similar pharmacokinetics and no significant differences on a number of clinical endpoints at weeks 14, 30 and 54. The 90% CI for the ratio of peak plasma concentrations between CT-P13 and Remicade were within the 80-125% margin for bioequivalence up to week 54. Additionally, the proportion of patients who developed antibodies against infliximab was similar between treatment groups through week 54. Treatment-related adverse events, infections and infestations, infusion-related reactions and serious adverse events were also similar between the groups. Celltrion published 30-week data from the trial in the Annals of the Rheumatic Diseases last month.CT-P13 is approved under the name Remsima in South Korea as a biosimilar of Remicade to treat rheumatoid arthritis (RA), Crohn's disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis and psoriasis. Celltrion said it expects a decision from EMA on an MAA for the product this month. The humanized mAb against tumor necrosis factor (TNF) alpha is partnered with Hospira Inc. (NYSE:HSP) in the U.S., Canada, EU, Australia and New Zealand and with Nippon Kayaku Co. Ltd. (Tokyo:4272) in Japan.

Study suggests efficacy of MDD therapy linked to glucose metabolism

Thu, 13 Jun 2013 00:00:00 -0700

Researchers at Emory University reported data from an open-label trial examining brain glucose metabolism in major depressive disorder (MDD) patients receiving generic escitalopram or cognitive behavior therapy (CBT) for 12 weeks. In 38 evaluable MDD patients, anterior insula hypometabolism was associated with remission to CBT but poor response to escitalopram, an allosteric selective serotonin reuptake inhibitor (SSRI). In contrast, anterior insula hypermetabolism was associated with remission to escitalopram but poor response to CBT. Data were published in JAMA Psychiatry.According to the Emory researchers, insula metabolism may serve as a pretreatment biomarker and would be the first objective marker to guide initial treatment of depression. The researchers said a prospective study in which patients are treated according to brain glucose metabolism is required to validate the results. Generic escitalopram is approved for MDD and generalized anxiety disorder (GAD) in adults. Forest Laboratories Inc. (NYSE:FRX) markets it as Lexapro in the U.S., while partner H. Lundbeck A/S (CSE:LUN) markets the drug in the EU as Cipralex.

Friends of Cancer Research planning lung cancer trial

Thu, 13 Jun 2013 00:00:00 -0700

Early next year, Friends of Cancer Research plans to start a Phase II/III trial of three or four investigational compounds as second-line treatments for advanced, stage IIIB or stage IV squamous cell carcinoma of the lung. Friends of Cancer Research said it has formed a drug selection committee that comprises individuals from FDA and NIH's National Cancer Institute, as well as academia and industry. The not-for-profit advocacy group said next steps include writing the trial protocol and working with companies to select the compounds for the trial.

Clovis raises $240M in bumped-up follow-on

Wed, 12 Jun 2013 00:00:00 -0700

Clovis Oncology Inc. (NASDAQ:CLVS) raised $240 million through the sale of 3.3 million shares at $72 in a bumped-up follow-on underwritten by JPMorgan; Credit Suisse; and Leerink. Clovis said it planned to raise $170 million in the offering Monday, when its share price was $71.83. The company's shares added 96% last week after Clovis presented Phase I data for two cancer compounds at the American Society of Clinical Oncology meeting in Chicago (see BioCentury, June 10). Clovis has rights to CO-1686 from Avila Therapeutics Inc., which Celgene Corp. (NASDAQ:CELG) acquired, as well as exclusive, worldwide rights to rucaparib from Pfizer Inc. (NYSE:PFE). CO-1686 is a small molecule that inhibits the T790 EGFR mutant and the initial activating EGFR mutations, and rucaparib is an oral inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1) and PARP-2. On Wednesday, Clovis was down $2.73 to $72.10

PeptiDream up in trading debut

Wed, 12 Jun 2013 00:00:00 -0700

PeptiDream Inc. (Tokyo:4587) closed at Y9,200 on Wednesday, its second day of trading on the Tokyo Stock Exchange's market of the high-growth and emerging stocks (Mothers). The close is a 268% gain from the Y2,500 price at which PeptiDream sold shares in its IPO. According to the company, trading of its shares was halted at Y5,750 in the first day of trading on Tuesday due to the exchange's daily price limits. PeptiDream raised Y5.3 billion ($52.4 million) through the sale of 2.1 million shares in an IPO. The company's Peptide Discovery Platform System (PDPS) enables incorporation of modified unnatural amino acids into mRNA display peptide libraries. The company has active target discovery deals with nine companies (see BioCentury, June 10).

Biogen Idec slides on analyst downgrade

Wed, 12 Jun 2013 00:00:00 -0700

Biogen Idec Inc. (NASDAQ:BIIB) fell $16.46 to $206.57 on Wednesday after a Citi analyst downgraded his rating of the company to neutral from buy on the belief that EMA is "unlikely" to grant regulatory data protection to Biogen Idec's multiple sclerosis drug Tecfidera dimethyl fumarate (BG-12). Citi's Yaron Werber, who said his conclusion is based on discussions with regulatory experts in Europe, said the lack of data protection for Tecfidera could lead to generic challenges that could pressure Tecfidera's pricing and market share in Europe. Biogen Idec's Wednesday move translates to a $3.9 billion loss in market cap for a closing valuation of $49 billion. Werber said he does expect Tecfidera to "substantially exceed estimates" in the U.S. in 2013; Biogen Idec launched the drug in April. Last month, Biogen Idec said it is delaying the launch of Tecfidera in Europe, where the drug is not yet approved, to next half to take "some time to clarify our regulatory data protection in the EU" (see BioCentury Extra, May 30).

Esperion sets IPO price range

Wed, 12 Jun 2013 00:00:00 -0700

Esperion Therapeutics Inc. (Plymouth, Mich.) amended its IPO and now plans to sell 4.5 million shares at $13-$15 in an IPO underwritten by Credit Suisse; Citigroup; JMP Securities; and Stifel Nicolaus Weisel. At the $14 midpoint, Esperion would raise $63 million and be valued at $197.1 million. The company filed to raise up to $70 million in the offering in May. Earlier this month, Esperion reported that once-daily oral ETC-1002 met the primary endpoint of reducing mean LDL-C from baseline to week eight vs. placebo in a Phase IIa trial to treat hypercholesterolemia (32% vs. 3%, p<0.0001). ETC-1002 is an AMP-activated protein kinase (AMPK) activator and ATP citrate lyase (ACL) inhibitor (see BioCentury Extra, June 7).

Celgene announces $3 billion repurchase program

Wed, 12 Jun 2013 00:00:00 -0700

Celgene Corp. (NASDAQ:CELG) said its board authorized the repurchase of up to $3 billion in a share repurchase program. Celgene has repurchased about $1.8 billion shares this year and said it exhausted a prior $2.5 billion repurchase plan. The company had $3.5 billion in cash as of March 31. On Wednesday, Celgene was down $0.64 to $118.11.

Amgen reports Phase III PFS data for AMG 386

Wed, 12 Jun 2013 00:00:00 -0700

Amgen Inc. (NASDAQ:AMGN) said once-weekly trebananib (AMG 386) plus paclitaxel met the primary endpoint of improving median progression-free survival (PFS) vs. placebo plus paclitaxel in the Phase III TRINOVA-1 trial to treat recurrent ovarian, primary peritoneal and fallopian tube cancer (7.2 vs. 5.4 months, p<0.001). Amgen said that a pre-planned interim analysis of the secondary overall survival (OS) endpoint showed a trend in favor of trebananib. Final OS data are expected to mature next year. The double-blind, international trial enrolled over 900 women with recurrent partially platinum-sensitive or platinum-resistant ovarian cancer, primary peritoneal cancer or fallopian tube cancer.TRINOVA-1 is the first of three Phase III trials evaluating trebananib in ovarian cancer. Data from the Phase III TRINOVA-2 trial evaluating trebananib plus doxorubicin for recurrent epithelial ovarian, primary peritoneal or fallopian tube cancer are expected next year, while data from the Phase III TRINOVA-3 trial of trebananib plus paclitaxel and carboplatin as first-line treatment of epithelial ovarian, primary peritoneal or fallopian tube cancer are expected in 2016. Trebananib is a recombinant Fc-peptide fusion protein (peptibody) targeting angiopoietins.Amgen was off $1.58 to $96.35 on Wednesday.

Amgen's brodalumab meets psoriatic arthritis endpoint

Wed, 12 Jun 2013 00:00:00 -0700

Amgen Inc. (NASDAQ:AMGN) and AstraZeneca plc (LSE:AZN; NYSE:AZN) said subcutaneous brodalumab met the primary endpoint compared to placebo in a Phase II trial to treat psoriatic arthritis. Both 140 and 280 mg subcutaneous brodalumab (formerly AMG 827) given once every two weeks improved ACR20 response rate at week 12 vs. placebo (37% and 39%, respectively, vs. 18%, p<0.05 for both). In biologic-naïve patients, ACR20 response rates were 36% for low-dose brodalumab, 37% for high-dose brodalumab and 20% for placebo. In patients with prior biologic exposure, ACR20 response rates were 37% for low-dose brodalumab, 42% for high-dose brodalumab and 16% for placebo. The double-blind, U.S. and Canadian trial enrolled 159 evaluable adults. Amgen said updated data from the trial are slated to be presented on Thursday at the European League Against Rheumatism meeting in Madrid. Next year, the partners plan to start Phase III testing of brodalumab for psoriatic arthritis. The humanized mAb against IL17R is also in Phase III testing for psoriasis and Phase II testing for asthma. Amgen and AstraZeneca partnered in April 2012 to jointly develop and commercialize five mAbs from Amgen, including brodalumab (see BioCentury, April 9, 2012). Amgen was off $1.58 to $96.35 on Wednesday.

VA researchers recommend delaying use of Enbrel for RA

Wed, 12 Jun 2013 00:00:00 -0700

Researchers at the Department of Veteran Affairs published a study that they said suggests a strategy of first administering a triple therapy of generics to treat adults with active rheumatoid arthritis (RA) before switching to a regimen with once-weekly Enbrel etanercept from Amgen Inc. (NASDAQ:AMGN) and Pfizer Inc. (NYSE:PFE). The researchers said the strategy -- where patients who do not have an adequate response to triple therapy would switch to Enbrel plus methotrexate -- will allow a "substantial percentage" of patients to be treated in a more cost-effective way without adversely affecting clinical outcomes. Amgen said in a statement that based on Enbrel's safety and efficacy, the company is "confident that [the drug] will remain a key tool to treat moderately to severely active rheumatoid arthritis." The VA told BioCentury it would be unable to respond in time for publication to a request for comment regarding whether or not it will change its treatment practices based on the study. The strategy recommended by the VA researchers is based on data from the double-blind RACAT trial, where initial therapy with once-weekly Enbrel as an add-on to methotrexate was non-inferior to initial therapy with the generics sulfasalazine and hydroxychloroquine as an add-on to methotrexate on the primary endpoint of reducing mean DAS28 score from baseline to week 48. There were also no significant differences between treatment arms on secondary endpoints, including radiographic progression, pain and health-related quality of life. Rates of adverse events were similar, though gastrointestinal disorders occurred more frequently with triple therapy, while infections and skin and subcutaneous disorders occurred more frequently with Enbrel plus methotrexate. The trial enrolled 353 RA patients with active disease despite methotrexate therapy; patients were switched in a blinded fashion at week 24 if they did not have an improvement according to a pre-specified threshold on their initial therapy. The study was published in the New England Journal of Medicine. Enbrel is approved to treat RA, juvenile idiopathic arthritis (JIA), ankylosing spondylitis, psoriatic arthritis and plaque psoriasis. Amgen and Pfizer co-market Enbrel in the U.S. and Canada, while Pfizer has rights elsewhere. In Japan, Pfizer co-markets Enbrel with Takeda Pharmaceuticals Co. Ltd. (Tokyo:4502).

Cytokinetics, Amgen expand heart failure deal to Japan

Wed, 12 Jun 2013 00:00:00 -0700

Cytokinetics Inc. (NASDAQ:CYTK) expanded to include Japanese rights a 2006 deal under which Amgen Inc. (NASDAQ:AMGN) has exclusive rights to Cytokinetics' cardiac contractility program. Amgen now has worldwide rights to develop and commercialize the program, of which the most advanced compound is omecamtiv mecarbil. An IV formulation of the small molecule cardiac myosin activator is in the Phase IIb ATOMIC-AHF trial to treat patients with left ventricular systolic dysfunction hospitalized for acute heart failure, with data expected this year. An oral formulation is in the Phase II COSMIC-HF trial to treat heart failure and left ventricular systolic dysfunction. Under the expanded deal, Cytokinetics will conduct a Phase I trial of omecamtiv mecarbil to support inclusion of Japanese patients in a potential Phase III program for the compound. Amgen, which is responsible for all development costs, will reimburse Cytokinetics for the trial.In exchange for expanding the deal to Japan, Cytokinetics will receive $15 million up front and is eligible for up to $50 million in additional milestones, plus royalties on Japanese sales. Cytokinetics is already eligible for up to $600 million in milestones under the original deal. Amgen also will purchase 8.4 million Cytokinetics shares for $1.19 per share, or $10 million. The price is a 6% discount to Cytokinetics' close of $1.27 on Tuesday, before the expansion was announced. Cytokinetics was up $0.13 (10%) to $1.40 on Wednesday, while Amgen was off $1.58 to $96.35.

Roche, GKV-Spitzenverband agree on Zelboraf price

Wed, 12 Jun 2013 00:00:00 -0700

Roche (SIX:ROG; OTCQX:RHHBY) and Germany's Statutory Health Insurance Funds Association (GKV-Spitzenverband) said they reached an agreement on the price for melanoma drug Zelboraf vemurafenib. The parties, who declined to disclose the negotiated price, said in a joint statement the negotiations were "not easy, but constructive and fair." The agreement comes after GKV-Spitzenverband said in late May that the price for Zelboraf had been determined through independent arbitration after the parties failed to agree on a price. Last year, Germany's Federal Joint Committee (G-BA) said Zelboraf has "significant" additional benefit over dacarbazine. The oral small molecule inhibitor of the oncogenic BRAF V600E is approved to treat patients with unresectable or metastatic melanoma who are BRAF V600-mutation positive (see BioCentury Extra, Sept. 6, 2012).

FDA publishes final rule clarifying 'orphan subset'

Wed, 12 Jun 2013 00:00:00 -0700

FDA published a final rule that clarifies language in Orphan Drug regulations, including when a compound may be eligible for Orphan Drug designation for a subset of patients with a non-rare disease. The final rule clarifies that a compound may be eligible for Orphan Drug designation for a subset of patients with a non-rare disease only if the company demonstrates that use of the compound in the broader population of the non-rare disease would be inappropriate due to certain properties of the compound, including toxicity, mechanism of action or previous clinical experience. FDA also clarified in the final rule that clinical superiority requirements for Orphan Drug designation are different than those for Orphan Drug exclusivity. FDA said it "liberally" grants Orphan Drug designation to products in development that show a plausible hypothesis of clinical superiority, but the agency said it reserves granting seven-year exclusivity to drugs that, upon approval, show clinical superiority to a previously approved drug. The final rule, which is largely in line with a proposed rule published in 2011, takes effect Aug. 12 (see BioCentury Extra, Oct. 20, 2011).

Dermira raises $35M in series B

Tue, 11 Jun 2013 00:00:00 -0700

Dermatology company Dermira Inc. (Redwood City, Calif.) raised $35 million in a series B round and a "related transaction" led by new investor Maruho Co. Ltd. (Osaka, Japan) and joined by existing investors Bay City Capital; New Enterprise Associates (NEA); and Canaan Partners. Dermira declined to disclose details. Dermira's lead program is lemuteporfin, a topical photosensitizer in Phase IIa testing to treat acne. Dermira gained lemuteporfin through its 2011 acquisition of Valocor Therapeutics Inc., which acquired rights from QLT Inc. (TSX:QLT; NASDAQ:QLTI) in May 2010 (see BioCentury, Jan. 23, 2012).

FDA to remove age restrictions on one-step emergency contraceptives

Tue, 11 Jun 2013 00:00:00 -0700

The Department of Justice said FDA will make Plan B One-Step levonorgestrel, a single-dose formulation emergency contraceptive from Teva Pharmaceutical Industries Ltd. (NYSE:TEVA), available OTC without any age restrictions but will maintain restrictions on two-pill versions. In a letter to Judge Edward Korman of the U.S. District Court for the Eastern District of New York, DoJ said it intends to withdraw its appeal of Korman's April order compelling FDA to make one-step emergency contraceptives available OTC without any age restrictions. DoJ said FDA will maintain age restrictions on the two-pill version of Plan B and its generic equivalents. The two-pill product is approved as a nonprescription drug for women age 17 and older, while younger women must have a prescription. According to DoJ, the sNDA submitted by Teva to allow for OTC sale of Plan B One-Step to those age 15 and over with proof of age "contained actual use data specifically addressing the ability of adolescents, including younger adolescents, to understand and follow the directions for safe and effective use as a nonprescription product" and that there are fewer data available on use of the two-pill version by younger adolescents. FDA approved the sNDA on April 30 (see BioCentury Extra, April 30). DoJ said FDA asked Teva to "promptly" submit an sNDA with proposed labeling to make Plan B One-Step available OTC without age restrictions and that FDA would approve the sNDA "without delay." FDA said it will need to determine the scope of any exclusivity after approval of Teva's sNDA and that its decision could affect labeling approved for generic equivalents of Plan B One-Step. Earlier this month, the U.S. Court of Appeals for the Second Circuit denied DoJ's request for a stay of Korman's order for two-pill versions, requiring FDA to make them available OTC without any age restrictions. DoJ said its decision is in compliance with the court's order because Korman authorized FDA to comply by making Plan B One-Step and not the two-pill version available if the agency believed there to be a significant difference between the two (see BioCentury Extra, June 5). Teva was down $0.17 to $39.83 on Tuesday.

FDA establishes GAIN qualifying pathogens

Tue, 11 Jun 2013 00:00:00 -0700

FDA issued a proposed rule listing pathogens that would be eligible for drug development incentives under the Generating Antibiotic Incentives Now (GAIN) Act. The pathogens are: species of Acinetobacter, Aspergillus, Campylobacter, Candida, Enterococcus and Pseudomonas as well as Clostridium difficile, Enterobacteriaceae, Neisseria gonorrhoeae, Neisseria meningitidis, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Vibrio cholerae, the Burkholderia cepacia complex of species, the Mycobacterium tuberculosis complex of species and non-tuberculous Mycobacteria species. FDA is required to consider four factors in establishing and maintaining the list: impact on the public health due to drug-resistant organisms in humans, rate of growth of drug-resistant organisms, increase in resistance rates, and morbidity and mortality. Comments on the rule are due 60 days after publication in the Federal Register, which is expected Wednesday. GAIN was signed into law last year as part of PDUFA V legislation (see BioCentury, Nov. 19, 2012).

BMJ: industry, regulators downplay antidiabetic concerns

Tue, 11 Jun 2013 00:00:00 -0700

The British Medical Journal published a report that says companies have not done "critical safety studies" to address concerns that glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors -- collectively known as incretin mimetics -- could cause pancreatitis and pancreatic cancer. The report also notes that regulators have not requested such studies. The report follows announcements in March by both FDA and EMA that the agencies are investigating data showing the Type II diabetes therapies may be associated with an increased risk of pancreatitis and pre-cancerous cellular changes called pancreatic duct metaplasia (see BioCentury, March 26).Separately, the American Diabetes Association called on companies developing or marketing incretin mimetics to make patient-level data available for an independent review to "help settle the question of whether such therapies contribute to the development of pancreatitis or pancreatic cancer." Marketed drugs mentioned in the BMJ article include Byetta exenatide from Bristol-Myers Squibb Co. (NYSE:BMY), Victoza liraglutide from Novo Nordisk A/S (CSE:NOVN; NYSE:NVO) and Januvia sitagliptin from Merck & Co. Inc. (NYSE:MRK). Neither FDA, EMA, nor the companies could be reached for comment.

Forest adds Icahn nominee to board

Tue, 11 Jun 2013 00:00:00 -0700

Forest Laboratories Inc. (NYSE:FRX) named Vincent Intrieri a director as part of a deal with activist investor Carl Icahn to avoid a proxy contest for the third straight year. The addition of Intrieri, a former director of Icahn Enterprises L.P., expands Forest's board to 11 members. Intrieri will also become the fifth member of an independent committee overseeing the succession plan for President and CEO Howard Solomon, who will retire at the end of the year.Icahn also agreed to not acquire more than 15% of Forest's stock for at least one year. In an SEC filing Tuesday, Icahn disclosed ownership of 30.7 million shares or about 11.5% of Forest based on 266.7 million shares outstanding on May 22. Forest was off $1.20 to $39.83 on Tuesday (see BioCentury Extra, Aug. 15, 2012).

FDA to hold Relistor panel

Tue, 11 Jun 2013 00:00:00 -0700

Salix Pharmaceuticals Inc. (NASDAQ:SLXP) said FDA will convene an advisory committee meeting to discuss the biotech's appeal of a complete response letter for subcutaneous Relistor methylnaltrexone to treat opioid-induced constipation (OIC) in patients with chronic pain. Salix said FDA requested additional clinical data in the July 2012 letter, but the company believed existing data were sufficient for approval of the sNDA. Salix said a conclusion on the appeals process could be reached this year; though a meeting date has not yet been set (see BioCentury Extra, May 9).Salix expects the panel to discuss the available safety data for Relistor, a peripheral mu opioid receptor (OPRM1; MOR) antagonist, and the strength of a cardiovascular safety signal seen with another drug in the class. Salix also expects discussion of the potential for MOR antagonists to trigger withdrawal symptoms and the need for and timing of major cardiovascular events (MACE) studies. Salix said FDA indicated it will seek advice from pain, gastrointestinal, safety and cardiovascular experts.Relistor is already approved in more than 55 countries, including the U.S., to treat OIC in patients receiving palliative care when response to laxative therapy has not been sufficient. Salix has worldwide rights to Relistor from Progenics Pharmaceuticals Inc. (NASDAQ:PGNX), which was up $1.14 (31%) to $4.82 on Tuesday. Salix was up $3.13 to $65.42.

NICE backs Jetrea for some with vitreomacular traction

Tue, 11 Jun 2013 00:00:00 -0700

The U.K.'s NICE issued draft guidance recommending the use of Jetrea ocriplasmin from ThromboGenics N.V. (Euronext:THR) to treat vitreomacular traction (VMT) only in a subset of patients without an epiretinal membrane and who have severe symptoms. The committee concluded the incremental cost-effectiveness ratio (ICER) of Jetrea was "likely" to be no greater than £21,000 ($32,607) per quality-adjusted life year (QALY) for patients without an epiretinal membrane, which is a thin sheet of fibrous tissue that can develop on the macular area of the retina. NICE determined the ICER of Jetrea in patients with an epiretinal membrane would be £64,331-£67,666 ($99,887-$105,065) per QALY. The European Commission approved Jetrea in March to treat vitreomacular traction, including when associated with a macular hole of 400 µm or less in diameter. Comments are due July 3, with final guidance expected in October. ThromboGenics was off EUR 0.96 to EUR 30.60 on Tuesday. The Alcon Inc. ophthalmic unit of Novartis AG (NYSE:NVS; SIX:NOVN) has ex-U.S. rights to commercialize Jetrea. In January, ThromboGenics launched the recombinant microplasmin in the U.S. to treat symptomatic vitreomacular adhesion, a precursor to VMT.

Algeta, Avipep in thorium-conjugate cancer deal

Tue, 11 Jun 2013 00:00:00 -0700

Algeta ASA (OSE:ALGETA) and Avipep Pty. Ltd. (Parkville, Australia) partnered to develop a targeted thorium conjugate (TTC) combining Algeta's thorium-227, an alpha-particle emitting radionuclide, with an undisclosed Avibody from Avipep for solid tumors. Both partners will contribute financially to the one-year deal, which may be extended. Avibodies combine recombinant antibody fragments with two, three or four target binding regions. Algeta was down NOK8.50 to NOK220.60 on Tuesday. In January, Immunomedics Inc. (NASDAQ:IMMU) granted Algeta rights to develop a TTC comprised of thorium-227 linked to Immunomedics' epratuzumab for cancer (see BioCentury Extra, Jan. 28).

PwC's Lefteroff passes away

Tue, 11 Jun 2013 00:00:00 -0700

Tracy Lefteroff, global managing partner of the venture capital practice at PricewaterhouseCoopers, passed away on June 9. He was 59. Lefteroff also served on the boards of Stanford Venture Laboratory and the California Healthcare Institute. PwC said the funeral will be private and there is not a memorial fund at this time.

NASDAQ Biotech Index changes rebalancing procedures

Tue, 11 Jun 2013 00:00:00 -0700

NASDAQ OMX Group Inc. (NASDAQ:NDAQ) said it will change the methodology of the NASDAQ Biotechnology Index (NASDAQ:NBI) due to "considerable" growth in the biotech sector, "particularly in the last six months." Effective June 21, the index will be rebalanced each quarter so the maximum weight of any index security does not exceed 8% and no more than five securities are at that cap. Previously, the index was rebalanced if the single largest market cap index security was greater than 24% and if the collective weight of all index securities with weights greater than 4.5% was greater than 48% of the index. The exchange said the changes will ensure the index's securities are closer in line to their actual market caps. Additionally, the index will change to an annual evaluation in December from semi-annual evaluations in May and November. The index tracks the performance of NASDAQ-listed securities classified as either biotech or pharmaceutical according to the Industry Classification Benchmark (ICB). The index was down $0.58 to $1,860.46 on Tuesday and has gained $429.65 (30%) this year.

ReproCell sets IPO range

Tue, 11 Jun 2013 00:00:00 -0700

Stem cell company ReproCell Inc. (Yokohama, Japan) amended its IPO on the JASDAQ Growth Market of the Osaka Securities Exchange and now plans to sell 642,000 shares at Y2,830-Y3,200. At the Y3,015 midpoint, the company would raise Y1.9 billion ($19.7 million) and be valued at Y25 billion ($255.3 million). The final price will be determined on June 18, with the shares slated to start trading on June 26. SMBC Nikko Securities and seven other firms are underwriters. The company markets induced pluripotent stem cell (iPSC)-derived cardiomyocytes and neurons for drug discovery. It also markets media and reagents for embryonic stem cells and iPSCs.