FDA's Peripheral and Central Nervous System Drugs Advisory Committee recommended approval of once-daily suvorexant from Merck & Co. Inc. (NYSE:MRK) to treat insomnia. The panel concluded suvorexant is an effective sleep aid but suggested it should be given at lower starting doses than those Merck has proposed. The pharma is seeking a label recommending use of 20-40 mg suvorexant in non-elderly patients and 15-30 mg in elderly patients.
The panel voted 13-3, with one abstention, that starting doses of 20 mg and 15 mg are safe, but voted 8-7, with two abstentions, against the safety of doses up to 40 mg in non-elderly patients and 30 mg in the elderly because of concerns about daytime somnolence and narcolepsy-like syndrome. The advisory committee also voted 11-5, with one abstention, that Merck should not have to conduct additional pre-approval studies of a 10 mg dose, which FDA reviewers had suggested in briefing documents on Monday might be an appropriate starting dose. Merck evaluated a 10 mg dose in a Phase II trial, but not in its Phase III program (see BioCentury Extra, May 20).
On efficacy, FDA's committee voted 12-4, with one abstention, that suvorexant is effective for improving sleep onset and 14-0, with one abstention, that the product is effective for sleep maintenance. Merck has not disclosed the PDUFA date for suvorexant; a standard review would put the PDUFA date in September.
Portola Pharmaceuticals Inc. (NASDAQ:PTLA) raised $122.1 million and Alcobra Ltd. (NASDAQ:ADHD) raised $25 million after pricing their IPOs on Wednesday. Portola sold 8.4 million shares at $14.50, the mid-point of its proposed $13-$16 range. The price values the company at $491.3 million. Earlier this month, Portola had amended its IPO and said it planned to sell 6.9 million shares at $13-$16. Morgan Stanley; Credit Suisse; Cowen; William Blair; and Sanford C. Bernstein are underwriters. Portola's betrixaban is an oral Factor Xa inhibitor in Phase III testing for hospital and post-discharge prevention of venous thromboembolism (VTE) in high-risk acutely medically ill patients.
Alcobra sold 3.1 million shares at $8, below its proposed $10-$12 price range. The $8 price values the company at $89 million. Earlier this month, Alcobra had amended its IPO and said it planned to sell 2.3 million shares at $10-$12. Aegis Capital and Sunrise Securities are underwriters. Alcobra plans to start Phase III testing of MG01CI in the U.S. to treat ADHD in adults in 4Q13. MG01CI is an extended-release formulation of metadoxine.
Portola was up $0.65 to $15.15 in its first day of trading on Wednesday, and Alcobra was off $0.45 to $7.55.
Ironwood Pharmaceuticals Inc. (NASDAQ:IRWD) raised $136.5 million and NPS Pharmaceuticals Inc. (NASDAQ:NPSP) raised $87.2 million in follow-ons on Wednesday. Ironwood sold 10.5 million shares at $13 in a follow-on underwritten by JPMorgan; BofA Merrill Lynch; Morgan Stanley; Cowen; Ladenburg; and Mizuho, while NPS sold 6 million shares at $14.53 in a follow-on underwritten by JPMorgan; Morgan Stanley; Canaccord; Leerink; Oppenheimer; and Wedbush. Ironwood had proposed to sell 10.5 million shares and NPS had proposed to sell 6 million shares late Monday, when Ironwood's share price was $13.83 and NPS's share price was $14.11.
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 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 down $0.58 to $12.91 on Wednesday. NPS was up $0.42 to $14.95 on the day.
HHS's Biomedical Advanced Research and Development Authority (BARDA) awarded GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) $40 million for an initial 18-month period to develop GSK's portfolio of antibacterial candidates to treat illnesses caused by bioterrorism agents and antibiotic resistance. If GSK and BARDA renew the partnership, the pharma is eligible for up to $200 million in total for a five-year period. HHS said the award is the first where BARDA is working with a company as "strategic partners with a portfolio approach," instead of providing funding for a contract for a single medical countermeasure.
Under the deal, GSK researchers will conduct safety and toxicology testing, clinical pharmacology studies, and clinical and non-clinical testing for the pharma's candidates in the portfolio. A joint oversight committee will conduct semi-annual reviews to monitor progress, make decisions on allocating the funding and to determine which GSK candidates should remain or be included in the portfolio, which initially includes GSK's GSK2140944. The bacterial topoisomerase IIA (TOP2A) inhibitor has been evaluated in preclinical studies for anthrax, plague and tularemia and is in Phase I testing as a broad-spectrum antibiotic. GSK also plans to develop GSK2140944 to treat hospital- and community-acquired drug-resistant bacterial infections.
Robin Robinson, director of BARDA, and Luciana Borio, assistant commissioner for counterterrorism policy at FDA and director of the agency's Office of Counterterrorism and Emerging Threats, will appear this Sunday on BioCentury This Week television.
FDA's Drug Safety and Risk Management Advisory Committee will meet on July 10 to discuss the REMS with elements of safe use (ETASU) for Lotronex alosetron from GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) and partner Prometheus Laboratories Inc., a unit of Nestle S.A. (SIX:NESN). Lotronex's ETASU require healthcare providers to be specially certified and enrolled in a prescribing program. Additionally, patients must sign a form acknowledging the risks of the product, and pharmacists can only fill paper prescriptions bearing a sticker showing the prescriber is certified in the program. The committee will discuss whether the REMS with ETASU assures safe use, is not unduly burdensome to patient access and minimizes burden to the health care delivery system.
ETASU may be required when FDA determines that a drug is effective but is associated with adverse events sufficiently serious that it would be unsafe to approve without safe use strictures. Lotronex is approved to treat women with severe diarrhea-predominant irritable bowel syndrome. The serotonin (5-HT3) receptor antagonist was withdrawn from the market in 2000 following reports of ischemic colitis and serious constipation complications, but FDA reapproved the drug with new restrictions in 2002 (see BioCentury, June 10, 2002).
AMAG Pharmaceuticals Inc. (NASDAQ:AMAG) fell $2.68 (11%) to $22.40 on Wednesday after disclosing in an SEC filing that partner Takeda Pharmaceutical Co. Ltd. (Tokyo:4502) is recalling a batch of anemia drug Rienso ferumoxytol from the Swiss market. According to AMAG, the decision was based on four reports of hypersensitivity reactions, including one fatality. AMAG said the companies are investigating the recalled batch of the IV iron replacement therapy, which the company said only affects the Swiss market, and the reported adverse events.
In April, AMAG said it expects to record 2013 net sales in the U.S. of Rienso, where it is known as Feraheme, of $63-$67 million. The drug, the company's only marketed product, is approved in the U.S., EU, Switzerland and Canada to treat iron deficiency anemia in chronic kidney disease (CKD) patients. Takeda, which has Swiss and European rights to Rienso under an amended 2010 deal, does not break out sales of the product.
Salix Pharmaceuticals Inc. (NASDAQ:SLXP) said budesonide rectal foam given twice daily for two weeks and then once daily for four weeks met the primary endpoint in a pair of Phase III trials to treat ulcerative colitis (UC). Budesonide rectal foam led to a greater proportion of patients achieving remission at the end of six weeks of treatment or withdrawal vs. placebo foam. The identical trials enrolled patients with active mild to moderate ulcerative proctitis or ulcerative proctosigmoiditis.
Salix plans to submit by the end of September an NDA to FDA for budesonide rectal foam to treat ulcerative proctitis, UC limited to the rectum, and ulcerative proctosigmoiditis, UC in the rectum and sigmoid colon. Dr. Falk Pharma GmbH (Freiburg, Germany) markets the product -- a foam formulation of budesonide, a glucocorticosteroid -- for the indications in Europe. Salix has exclusive rights from Dr. Falk to develop and commercialize budesonide products in the U.S.
Salix was up $0.14 to $59.47 on Wednesday.
Upsher-Smith Laboratories Inc. (Maple Grove, Minn.) said on Wednesday that once-daily USL255 as adjunctive therapy met the primary endpoint in the Phase III PREVAIL trial, and that FDA accepted for review an NDA for USL255 as adjunctive treatment of epilepsy in patients with refractory partial-onset seizures. In the trial, USL255 reduced from baseline weekly partial-onset seizure frequency during the titration plus maintenance phase vs. placebo (p<0.001). The double-blind, international trial enrolled more than 200 epileptic patients. Upsher-Smith, which has an SPA from FDA for the trial, said the data will be submitted for presentation at the American Epilepsy Society meeting in December.
The company declined to disclose the specific PDUFA date for USL255, but said it expects a decision in December. USL255 is an extended-release formulation of topiramate, a sodium channel blocker, GABA receptor agonist and AMPA receptor antagonist.
The U.S. Senate Health, Education, Labor and Pensions (HELP) committee agreed by voice vote on Wednesday to send to the full Senate a bill that would streamline drug tracking and make compounding manufacturers subject to stricter regulation by FDA. The committee voted to incorporate the previously separate Drug Supply Chain Security Act into the Pharmaceutical Compounding Quality and Accountability Act. The joint bill, S. 959, would create an electronic, unit-level system for tracking and tracing pharmaceutical products to be phased in over 10 years. The bill also would define compounding manufacturers as entities that make sterile products without or in advance of a prescription and sell those products across state lines. It would enable FDA to specify drugs that cannot be compounded, including biologics and drugs with complex formulations. A vote by the full Senate on the combined bill has not yet been scheduled (see BioCentury Extra, May 15).
The HELP committee released an accompanying report on Wednesday on the risk to public health of large-scale drug compounding. The report calls for the enactment of a "clear statutory framework" requiring compounding manufacturers to follow "appropriate good manufacturing practices."
The U.S. House of Representatives is also considering a bill to create a national system for tracking and tracing pharmaceutical products, though a vote on that bill has not yet been scheduled. The House bill does not call for unit-level tracing to be phased in over 10 years (see BioCentury Extra, May 15).
Personalized medicine has "come of age," but a number of scientific and policy challenges must be overcome before it can mature, Janet Woodcock, director of FDA's Center for Drug Evaluation and Research, said Tuesday at a meeting of the Personalized Medicine Coalition.
Woodcock, who noted that one-third of NME submissions in 2012 contained genome biomarker data, predicted drug labels will increasingly contain genomic data and said drug developers, pathologists and regulators will have to work hard to make labels useful to clinicians. "When I talk to the medical community about targeted therapies, they are very clear on what they want. They want directions; they don't want education. They want to know 'What do I do?'"
Woodcock said success in more precisely defining populations who can benefit from a drug has led to "startling" efficacy results that are the basis for the agency's recent breakthrough designations. The identification of "ever-smaller" subpopulations, however, means that "we have to put our heads together and figure out how do you study these smaller subsets of disease," she said. Approving drugs based on mechanistic reasoning, and moving away from randomized controlled trials for drugs targeted at small subpopulations will require a "huge intellectual lift" at FDA, added Woodcock.
She also noted that in many cases, early, strong efficacy signals from targeted therapies are not durable, which suggests that to create interventions that cure or provide long-term control of disease, companies will have to work together to test combinations.
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