FDA's Endocrinologic and Metabolic Drugs Advisory Committee voted 13-1 that the benefit-risk profile of dapagliflozin from Bristol-Myers Squibb Co. (NYSE:BMY) supported approval as an adjunct to diet and exercise to treat Type II diabetes. The panel also voted 10-4 that the pharma had demonstrated an acceptable cardiovascular risk profile for the sodium-glucose cotransporter 2 (SGLT2) inhibitor.
The vote was an about face from a 2011 panel meeting in which members voted 9-6 against approval of dapagliflozin due to concerns about the risks of bladder and breast cancer as well as hepatotoxicity. Four of the panel members from the 2011 meeting were present at Thursday's meeting and backed dapagliflozin, including three who had previously voted no.
The returning members along with the rest of the panel agreed that Bristol-Myers had addressed the safety concerns with additional data from animal toxicology studies and extension studies. Additionally, they felt that the benefits of reductions in HbA1c, blood pressure and body weight seen in the clinical program outweighed these concerns. The panel did recommend that the company collect data postmarket to further characterize the risks.
Dapagliflozin is partnered with AstraZeneca plc (LSE:AZN; NYSE:AZN). The drug -- which the European Commission approved as Forxiga in November 2012 -- has a Jan. 11 PDUFA date.
Emergent BioSolutions Inc. (NYSE:EBS) will acquire Cangene Corp. (TSX:CNJ) for US$3.24 per share in cash, or about $222 million. The price is a 28% premium to Cangene's close of C$2.70 ($2.53) on Wednesday, before the deal was disclosed. The deal -- which is subject to approval by Cangene shareholders but has been approved by the boards of both companies -- is slated to close next quarter. BofA Merrill Lynch advised Emergent, and Credit Suisse advised Cangene.
Emergent said the acquisition will strengthen its biodefense franchise and broaden its manufacturing capabilities. Emergent provides its BioThrax anthrax vaccine to the U.S. Strategic National Stockpile under a government contract worth up to $1.3 billion. The company will gain three Cangene products also included in the stockpile, including botulism antitoxin heptavalent (BAT), which is approved in the U.S. for symptomatic botulism. Other products Emergent will gain include Cangene's WinRho SDF, which is approved in the U.S. and EU to treat immune thrombocytopenia purpura (ITP); and HepaGam B, which is approved in the U.S., Canada and Israel to prevent recurrence and for prophylaxis of HBV infection. Emergent will also gain Cangene's contract manufacturing operations.
Cangene reported $127.3 million in revenues for the fiscal year ending July 31. The company was up C$0.72 (26%) to C$3.42 on Thursday. Emergent, which reported 2012 revenues of $281.9 million, was up $1.14 to $22.45 on the day.
FDA's Allergenic Products Advisory Committee voted 9-0 on Thursday that available data support the efficacy of Grastek grass Allergy Immunotherapy Tablet (AIT) from Merck & Co. Inc. (NYSE:MRK) to treat Timothy grass pollen induced allergic rhinitis, with or without conjunctivitis, in individuals five years of age and older. The panel also voted unanimously that available data support the safety of the tablet-based sublingual allergen immunotherapy when administered with the understanding that auto-injected epinephrine will be made available at home.
Merck said it expects an FDA decision on Grastek in 1H14. The pharma has exclusive North American rights to develop and commercialize the product from ALK-Abello A/S (CSE:ALK-B), which markets it as Grazax in Europe. ALK-Abello was up DKK9 to DKK612 on Thursday. The vote came after market close in Denmark.
On Wednesday, the advisory committee voted 9-1 that available data support the efficacy of Oralair from Stallergenes S.A. (Euronext:GENP) to treat grass pollen-induced allergic rhinoconjunctivitis in individuals five years of age and older when administered prior to and during the grass pollen season. The panel unanimously voted that available data support safety in individuals 10-65 years of age with the understanding that auto-injected epinephrine will be made available at home, and 5-5 that available data support the safety of Grastek in children five to nine years of age when administered with the understanding that auto-injected epinephrine will be made available at home.
Oralair is a sublingual immunotherapy against five grass allergens. Stallergenes, which is not disclosing when it expects a decision, was up EUR 0.69 to EUR 54.50 on Thursday. The vote came after market close in France on Wednesday. FDA said one voting member who attended Wednesday's Oralair meeting was unable to attend the Grastek meeting on Thursday.
The Obama administration's decision to extend the deadline for purchasing insurance from a federal- or state-run exchange is likely to cause problems for consumers and insurance companies in January, according to American Enterprise Institute scholar Joe Antos. Due to problems with HealthCare.gov, the federal healthcare exchange website, the White House pushed back to Dec. 23 from Dec. 15 the deadline for purchasing insurance policies that become effective Jan. 1. The new deadline doesn't provide insurance companies sufficient time to process orders and confirm the identity of customers, Antos said. As a result, many consumers who purchase insurance on an exchange close to the deadline may find it impossible to access care in early January. "Rolling into January, there are going to be thousands of people who will go to the doctor and find they are not on the books. That's going to be a traumatic experience for many people," Antos noted.
Paul Keckley, a healthcare analyst and former executive director of the Deloitte Center for Health Solutions, predicted that many people who purchase insurance in the marketplaces will have difficulties obtaining coverage in January. Documenting enrollment between Dec. 23 and Jan. 1 is "an astronomical mountain for the insurance companies to climb," Keckley said. "I expect it will be ugly."
Antos, Keckley and Judy Feder, a professor at the Georgetown Public Policy Institute, will discuss implementation of the Affordable Care Act, including the possibility of coverage glitches, on the Dec. 15 edition of BioCentury This Week television. The program will be broadcast at 8:30 a.m. in Washington, D.C., on WUSA, channel 9. It will be available at www.BioCenturytv.com beginning at 9 a.m., and also will be broadcast on selected PBS stations.
A bipartisan group of representatives introduced in the U.S. House of Representatives a bill that would create an accelerated approval pathway for antibiotics and antifungals for use in limited populations and would update the criteria that HHS uses to determine breakpoints for drugs. Under the Antibiotic Development to Advance Patient Treatment (ADAPT) Act, FDA could approve antibiotics and antifungals for limited populations based on a smaller number of patients or alternative endpoints, as well as data from Phase II trials or pharmacologic or pathophysiologic data. The Infectious Diseases Society of America (IDSA) first proposed the approval pathway. Though new legislative authority is not needed to implement the pathway, stakeholders have said congressional enactment of the regulatory framework could be valuable (see BioCentury Extra, July 31).
IDSA expressed support for ADAPT but recommended amending the bill to include a logo requirement to clearly mark drugs approved under the pathway. Currently, a label would only include a statement noting the drug is intended for use in a limited population. In a letter to the sponsors, the Pew Charitable Trusts also recommended legislators "strengthen" labeling requirements for drugs approved under the proposed pathway and limit the pathway to bacterial infections (see BioCentury, Jan. 28).
ADAPT would also require HHS to conduct quarterly reviews of new breakpoint data, including pharmacokinetic, pharmacodynamic and epidemiological data, and make necessary updates to drug labels. A breakpoint is defined as the concentration of a drug at which a given pathogen is susceptible or resistant to a particular antibiotic when used at the approved dose. Breakpoints are included on a drug's label and are generally based on preclinical and clinical data that are available at the time of approval (see BioCentury, Nov. 11).
The bill -- which also mandates that the Centers for Disease Control monitor antibiotic use and resistance including for drugs approved for a limited population -- was referred to the House Energy and Commerce Committee.
The European Commission announced the first calls for proposals under Horizon 2020, the EU research and innovation program for 2014-20. The first calls have a budget of more than EUR 15 billion ($20.6 billion) and cover funding opportunities for 2014-15. Horizon 2020 categorizes funding calls into broad research topics, in contrast to the EU's current research program, Framework Programme 7 (FP7), which categorizes funding calls based on specific research modalities. Based on BioCentury's analysis, Horizon 2020's first calls earmark at least EUR 1.1 billion ($1.5 billion) for 2014 and EUR 1 billion ($1.4 billion) for 2015 for broad research topics that contain subtopics that mention drug-related research.
The first calls also allocate EUR 485 million ($665.2 million) for the European Research Council (ERC) for grants to support investigators starting independent research teams or programs in the physical sciences and engineering, life sciences and social sciences and humanities. Horizon 2020, which has a total budget of EUR 78.6 billion ($106.1 billion), will replace FP7 when it expires at year end.
Separately, the EU's Innovative Medicines Initiative (IMI) launched its eleventh call for proposals with a budget of EUR 371 million ($508.8 million), of which IMI will provide EUR 170.4 million ($233.7 million) and participating member companies of the European Federation of Pharmaceutical Industries and Associations (EFPIA) will provide EUR 201 million ($275.7 million) through in-kind contributions. The eleventh call covers R&D for eight topics, including Alzheimer's disease (AD), antimicrobial resistance, osteoarthritis and cancer. Applications are due April 8, 2014.
The French Parliament passed a bill that would allow pharmacists to dispense a biosimilar in place of an innovator product to patients initiating treatment or who are already receiving treatment with a biosimilar. The provisions, included in a bill to set the country's social security budget for 2014, also would require pharmacists to alert prescribers of the substitution. Prescribers would be able to expressly rule out biosimilar substitution for reasons unique to the patient. The legislation also would charge the French National Agency for Drug Safety (ANSM) to create a directory of biosimilar products, which would list all approved biosimilars with the reference biologic. The bill is subject to review by the French Constitutional Coucil.
FDA said it is "reviewing options for making a publicly available list of licensed biosimilar products and interchangeable products," but the agency said it does not have a timeline for publishing the list. The agency also said it is "too early" to say whether the list will also contain patent and exclusivity information for innovator biologics. John Jenkins, director of the Office of New Drugs in FDA's Center for Drug Evaluation and Research, said earlier this week that the agency was planning to develop a guide like the Orange Book for biologics. The Orange Book lists all approved generic equivalents for a drug, along with its patent and exclusivity information.
A list of biologics and interchangeable biosimilars could help health providers and payers determine what biosimilars are available and make substitution decisions for patients. Biosimilar developers, manufacturers of originator biologics, payers and consumer groups are battling across the U.S. and worldwide on requirements for interchangeable biosimilar substitution (see BioCentury, Sept. 30).
The California Institute for Regenerative Medicine awarded $61 million across six grants to five California universities for projects focused on developing stem-cell based therapies for leukemia and solid tumors, sickle cell disease, macular degeneration and airway blockage. CIRM also approved and set aside $200 million for a new program aimed at speeding up development of projects already funded by CIRM. The program is intended for projects that are in or close to the clinic but need additional funding to get through a Phase II trial.
FDA Commissioner Margaret Hamburg announced in an internal memo that John Taylor will depart in January as counselor to the commissioner and acting deputy commissioner for global regulatory operations and policy. Taylor worked at FDA from 1991-2005 and rejoined the agency in 2009. Between his two stints at FDA, Taylor served as VP for federal government affairs at Abbott Laboratories (NYSE:ABT) and as EVP of health at the Biotechnology Industry Organization (BIO).
Specialty pharma Endo Health Solutions Inc. (NASDAQ:ENDP) raised $700 million through the sale of 5.75% senior unsecured notes due January 2022. Endo had proposed to raise $375 million in the offering early on Wednesday. The company -- which is acquiring fellow specialty pharma Paladin Labs Inc. (TSX:PLB) in a cash and stock deal -- was up $0.15 to $64.04 on Thursday (see BioCentury Extra, Nov. 5).
Cancer company TetraLogic Pharmaceuticals Corp. (NASDAQ:TLOG) raised $50.1 million in an IPO through the sale of 7.2 million shares at $7, which values TetraLogic at $147.8 million. On Tuesday, the company had amended the offering and said it planned to sell 6.5 million shares at $7. Late last month, TetraLogic was rumored to have postponed its IPO. Earlier in November, the company had amended its IPO and said it planned to sell 6.4 million shares at $13-$15. Oppenheimer; Guggenheim; and Needham are underwriters.
TetraLogic's birinapant (formerly TL32711) has completed a Phase I/II trial for colorectal cancer (CRC) and is in Phase I testing for myelodysplastic syndromes (MDS). The compound is a small molecule peptidomimetic of diablo homolog (DIABLO; SMAC) that selectively antagonizes multiple inhibitor of apoptosis (IAP) proteins. Next half, TetraLogic plans to start a Phase II trial for MDS.
TetraLogic was unchanged at $7 on its first day of trading Thursday.
Duchenne muscular dystrophy (DMD) companies Sarepta Therapeutics Inc. (NASDAQ:SRPT) and Prosensa Holding N.V. (NASDAQ:RNA) both jumped almost 20% on Thursday on comments and presentations made at the Duchenne Policy Forum. At the forum organized by patient advocacy group Parent Project Muscular Dystrophy, FDA and other stakeholders made presentations on topics including potential biomarkers and surrogate endpoints for DMD.
Sarepta, which closed up $3.30 (19%) to $20.71 on the day, said it was not involved with the forum; the company attributed the Thursday stock moves to "interest in moving forward with therapies for Duchennes." Prosensa Holding N.V. (NASDAQ:RNA) closed up $0.72 (18%) to $4.81. The company did have members present at the forum but declined to comment on the stock jumps. BioCentury was unable to obtain a copy of comments allegedly made at the forum by Janet Woodcock, director of FDA's Center for Drug Evaluation and Research. FDA did not provide a comment in time for publication.
Even with Thursday's gains, both Sarepta and Prosensa are still well below their highs prior to regulatory and clinical setbacks. Last month, Sarepta plummeted $23.40 (64%) to $13.16 after disclosing that FDA considers an NDA submission for the company's eteplirsen to treat DMD "premature" because of the use of dystrophin as a surrogate endpoint and the six-minute walk test (6MWT) data from Sarepta's open-label Phase IIb trial of eteplirsen. In September, Prosensa fell $16.86 (70%) to $7.14 after announcing that drisapersen, which is partnered with GlaxoSmithKline plc (LSE:GSK; NYSE:GSK), missed the primary endpoint in the Phase III DEMAND 3 (DMD114044) trial (see BioCentury Extra, Nov. 12).
Xoma Corp. (NASDAQ:XOMA) proposed a follow-on late Thursday underwritten by Credit Suisse; Jefferies; Cowen; Piper Jaffray; and RBC Capital Markets. Xoma's gevokizumab (XOMA 052) is in Phase III testing for non-infectious uveitis (NIU) and Behcet's uveitis, with top-line data expected next year. Partner Servier (Neuilly-sur-Seine, France) has worldwide rights to develop and commercialize the humanized IgG2 mAb against IL-1 beta for Type II diabetes and cardiovascular indications and rights outside the U.S. and Japan for all other indications.
Xoma, which proposed the offering after market close, was up $0.04 to $5.66 on Thursday.
Mallinckrodt plc (NYSE:MNK) said MNK-155 met the primary endpoint vs. placebo in a Phase III trial to manage moderate to severe acute pain where the use of an opioid analgesic is appropriate. In the double-blind trial, a loading dose of three tablets of oral MNK-155 followed by two tablets every 12 hours for 48 hours improved the summed pain intensity difference from baseline over 48 hours (SPID48) vs. placebo. The trial enrolled about 400 patients with moderate to severe acute pain following a unilateral first metatarsal bunionectomy.
Mallinckrodt said it plans to submit an NDA to FDA for MNK-155 in the second half of its fiscal year ending Sept. 26, 2014. The product is an extended-release oral formulation of hydrocodone and acetaminophen formulated using the AcuForm gastric retentive formulation technology from Depomed Inc. (NASDAQ:DEPO). Mallinckrodt is developing MNK-155 under section 505(b)(2) of the Food, Drug and Cosmetic Act, which allows sponsors to reference data on safety and efficacy from the scientific literature or from previously approved products.
On Thursday, Mallinckrodt was up $0.31 to $52.16.
Paul Keckley stepped down as executive director of the Deloitte Center for Health Solutions on Sept. 6. Wednesday's BioCentury Extra misstated his affiliation.