Synageva BioPharma Corp. (NASDAQ:GEVA) raised $211 million on Thursday through the sale of 2 million shares at $105.75 in the largest follow-on so far this year. The company proposed the offering late Tuesday, when its share price was $103.99. Goldman Sachs; JPMorgan; Morgan Stanley; Cowen; Canaccord; Baird; and Nomura Securities are underwriters.
Synageva's sebelipase alfa (formerly SBC-102) is in the Phase III ARISE trial for late onset lysosomal acid lipase (LAL) deficiency (cholesteryl ester storage disease), with data expected next half. By 1Q15, Synageva plans to submit a BLA to FDA and an MAA to EMA for the recombinant human LAL enzyme replacement therapy (ERT) to treat LAL deficiency.
Synageva was off $7.46 to $98.29 on Thursday.
The European Commission granted conditional approval to an MAA from Johnson & Johnson (NYSE:JNJ) for Sirturo bedaquiline to treat pulmonary multi-drug resistant tuberculosis (MDR-TB) in adults. The approval covers use of bedaquiline as part of a combination therapy when alternative treatments cannot be used due to resistance or intolerance. Bedaquiline also has accelerated approval from FDA for pulmonary MDR-TB as part of a combination therapy when other alternatives are not available (see BioCentury Extra, Jan. 2, 2013).
As part of both the conditional and accelerated approval, J&J plans to conduct a confirmatory Phase III trial of Sirturo that the pharma said will satisfy post-approval commitments from both agencies. The pharma said the protocol for the trial is still being finalized, but said the trial is slated to start this year. Sirturo is a diarylquinoline (DARQ) antibiotic.
FDA approved a resubmitted NDA from Endo International plc (NASDAQ:ENDP; TSX:ENL) for Aveed testosterone to treat male hypogonadism. The company said it plans to launch the product in the U.S. this month. Aveed's label includes a boxed warning on the risk of serious pulmonary oil microembolism reactions and anaphylaxis. Aveed was approved with a REMS requiring prescriber education and certification as well as restricted product distribution. The REMS also includes elements to assure safe use (ETASU).
In May 2013, FDA issued a complete response letter for Aveed and requested that Aveed's REMS include a medication guide and ETASU "to mitigate the risks and severe complications related to post-injection reactions." In the approval letter, FDA said it has since determined the medication guide is "not necessary to ensure the benefits of Aveed" outweigh its risks (see BioCentury Extra, May 30, 2013).
Endo has exclusive, U.S. rights to the long-acting depot preparation of testosterone undecanoate from Bayer AG (Xetra:BAYN), which markets the product outside the U.S. as Nebido.
Endo was off $2.58 to $73.89 on NASDAQ on Thursday. The company was off C$3.35 to C$81.15 in Toronto.
Life science entrepreneur Alejandro Zaffaroni passed away on March 1 at the age of 91. Zaffaroni founded a number of companies, including Affymetrix Inc. (NASDAQ:AFFX); Alexza Pharmaceuticals Inc. (NASDAQ:ALXA); and Alza Corp., which Johnson & Johnson (NYSE:JNJ) acquired. The family requested that donations in Zaffaroni's memory be made to the Alejandro and Lida Zaffaroni Scholarship and Fellowship Program at Stanford University, the University of California, Berkeley Foundation and the Boys and Girls Clubs of the Peninsula.
Roche (SIX:ROG; OTCQX:RHHBY) said William Pao will join its Pharma Research and Early Development (pRED) division as global head of the oncology disease and translational area, effective May 1. Pao is a professor of medicine at Vanderbilt University Medical Center. He also is director of the center's Division of Hematology/Oncology and Personalized Cancer Medicine unit.
Diagnostic company Sequenom Inc. (NASDAQ:SQNM) said Harry Hixson will retire as CEO, effective at the company's annual meeting on June 10. President and COO William Welch will succeed Hixson, who will continue to serve as Sequenom's chairman. Welch will be nominated to the board. Additionally, CFO Paul Maier will also retire, effective June 10. Carolyn Beaver, VP and chief accounting officer, will become CFO. Sequenom also said Dirk van den Boom, EVP of R&D and CSO, will be promoted to chief scientific and strategy officer.
Sequenom was off $0.02 to $2.33 on Thursday.
Stallergenes S.A. (Euronext:GENP) reported 2013 financial results and named Christian Chavy as CEO, effective March 31. Chavy, a Stallergenes director and partner at healthcare investment fund Ares Life Science, will replace Roberto Gradnik. Before that, Chavy was in charge of global operations at Actelion Ltd. (SIX:ATLN). Stallergenes reported 2013 revenues of EUR 248.1 million ($341.8 million), up 4% from EUR 239.8 million ($330.4 million) in 2012. The company said it expects revenue growth in the low single-digit for 2014 and said it expects a decision from FDA by the end of the month on Oralair, which is under review to treat grass pollen-induced allergic rhinoconjunctivitis.
Stallergenes was up EUR 2.81 to EUR 56.46 on Thursday.
FDA rescheduled for March 27 a meeting of its Cardiovascular and Renal Drugs Advisory Committee to discuss a BLA from Novartis AG (NYSE:NVS; SIX:NOVN) for serelaxin (RLX030) to treat acute heart failure (AHF). The meeting was originally scheduled for Feb. 13, but was postponed due to weather. The recombinant human relaxin-H2 has FDA breakthrough therapy designation for the indication.
In January, EMA's CHMP recommended against approval of serelaxin to treat AHF, citing uncertainties about serelaxin's benefits. Novartis said it plans to submit and request a reexamination of a revised application that includes new analyses (see BioCentury Extra, Jan. 24).
The BioCentury 100 Index lost 166.21 points, or 2.8%, to 5,714.16 on Thursday, while the broader markets remain relatively flat. The BC100 is a price-weighted index of top U.S.-listed biotechs by market cap. The days big decliners included Gilead Sciences Inc. (NASDAQ:GILD), which fell $2.95 (4%) to $79.92 on the day, and Celgene Corp. (NASDAQ:CELG), which closed off $6.63 (4%) to $156.61.
Other healthcare indices also fell on Thursday. The NYSE Arca Biotechnology 2.5% and the NASDAQ Biotechnology fell 2.6%. The NYSE Arca Pharmaceutical Index slid only 0.4%. There was no obvious news catalyst for the selloff. In a note on Thursday's slide, ISI's Mark Schoenebaum said a massive sell-off in biotech is "unlikely" but said a "more modest correction is, in theory possible, since all the stocks now trade above conservative [discounted cash flow] analyses."
The broader markets were relatively flat on Thursday. The S&P 500 closed up 0.2%, the NASDAQ was off 0.1% and the Dow Jones Industrial Average was up 0.4%.
Gene therapy play Sangamo BioSciences Inc. (NASDAQ:SGMO) jumped $3.35 (17%) to $22.96 on Thursday following the release of data from two trials evaluating the company's SB-728-T (formerly CCR5-ZFN) to treat HIV. Researchers at the University of Pennsylvania published data in the New England Journal of Medicine showing one patient who received a single infusion of SB-728-T had HIV RNA rise and then fall back down to undetectable levels during interruption of treatment with highly active anti-retroviral therapy (HAART). All patients in the Phase I trial had undetectable HIV RNA levels at the start of the 12-week interruption of HAART. The other three patients also completing the interruption saw HIV RNA levels increase, peaking at weeks 6-8 and then fall again. In all four patients, the average reduction in HIV RNA was 1.2 log from peak levels during the treatment interruption (p=0.07).
Sangamo also presented additional data from three cohorts in the Phase I/II SB-728-1101 trial showing that increasing doses of IV cyclophosphamide administered prior to a single infusion of SB-728-T increased engraftment of the cells and increased viral load reduction during HAART interruption. The trial enrolled patients with stably controlled undetectable viral load on HAART who stopped HAART six weeks after the SB-728-T infusion if CD4 T cell counts were 500 cells/mm3 or greater. The data were presented at the Conference on Retroviruses and Opportunistic Infections meeting.
SB-728-T is a cell therapy consisting of autologous CD4 T cells genetically modified at the CC chemokine receptor 5 (CCR5) gene by a zinc finger DNA binding protein nuclease (ZFN). This half, Sangamo expects to start a trial with a new manufacturing process that uses mRNA to deliver SB-728-T rather than viral delivery. Following the trial, Sangamo plans to partner SB-728-T for further development.
Boehringer Ingelheim GmbH (Ingelheim, Germany) reported data on Thursday from a Phase III trial evaluating faldaprevir (BI 201335) in patients with HCV genotype 1 infection co-infected with HIV and also said FDA accepted for review an NDA for the oral HCV NS3/4A protease inhibitor. In the 308-patient Phase III STARTVerso 4 trial, once-daily oral faldaprevir in combination with pegylated interferon and ribavirin led to an HCV sustained virologic response (SVR) 12 weeks after the end of treatment in 71% of patients who received 120 mg faldaprevir for 24 weeks (n=123) and 72% of patients who received 240 mg faldaprevir for 12 or 24 weeks (n=185).
The open-label trial enrolled patients co-infected with HCV and HIV who were HCV treatment-naïve or had relapsed after previous HCV therapy, and were either naïve to or stable on HIV therapy. Boehringer has twice reported data from STARTVerso 4 and expects to report SVR24 data from the trial this year.
The NDA for faldaprevir covers its use in combination with ribavirin and pegylated interferon to treat chronic HCV genotype 1 infection in adults who are treatment-naïve or have been previously treated with interferon-based treatment, as well as those with compensated liver disease, cirrhosis or HCV/HIV co-infection. Boehringer said it expects a decision in 4Q14; the company is not disclosing the specific PDUFA date. An MAA for faldaprevir is already under accelerated assessment by EMA.
Additionally, Boehringer said it discontinued development of deleobuvir, an oral NS5B RNA-dependent polymerase inhibitor, following an assessment of blinded data from the Phase III HCVerso 1 and 2 trials evaluating faldaprevir and deleobuvir in combination with ribavirin in treatment-naïve patients with HCV genotype 1b infection. Boehringer said the faldaprevir/deleobuvir combination "showed a higher rate of premature discontinuations suggesting a lower efficacy rate compared to other interferon-free therapies in development."
FDA is holding a public workshop on April 1 to obtain input on the use of high throughput sequencing devices to diagnose infectious diseases, including the detection of antimicrobial resistance markers. The agency is seeking stakeholder input on the clinical applications of the devices, including specific applications where high throughput sequencing could be used for diagnosis; and ways to validate device performance, including developing and adapting standards for the sequencing process.
FDA is also seeking input on developing quality criteria to ensure accuracy of reference databases. With high throughput sequencing devices, microbes or resistance markers are identified by comparing genomic sequence information to reference databases that are publicly available or were created by the company.
The U.S. Patent and Trademark Office issued updated guidance to patent examiners on determining whether product claims that involve natural phenomena and natural products are patent eligible. The updated guidance notes these claims are patent eligible only if they are "significantly different" from what exists in nature. The guidance provides a list of factors that "weigh toward eligibility," including elements or steps that "impose meaningful limits on claim scope" or "add a feature that is more than well-understood, purely conventional or routine in the relevant field." The updated guidance also provides several examples for patent examiners, including when methods or process patent claims would be appropriate.
The new guidance replace preliminary guidance that PTO issued last June after the U.S. Supreme Court ruled in Association for Molecular Pathology, et al. v. U.S. PTO, et al. that isolated DNA cannot be patented but cDNA can be patented. In the updated guidance, PTO said that "Myriad is a reminder that claims reciting or involving natural products should be examined for a marked difference" from the naturally occurring product (see BioCentury, June 17, 2013).
EMA and FDA agreed to extend by two years a pilot program for parallel assessment of Quality by Design (QbD) components of NDAs and MAAs. QbD is an approach using statistical, analytical and risk-management methodology in the design, development and manufacturing of medicines to ensure quality. One of the goals of the approach is to identify, explain and manage all sources of variability affecting a process. The EMA and FDA pilot program is intended to prevent the regulatory agencies from applying QbD standards inconsistently. The agencies reviewed one application for an undisclosed product from Pfizer Inc. (NYSE:PFE) and "several" scientific advice requests under the original three-year pilot program, which has run since April 2011.