Enanta Pharmaceuticals Inc. (NASDAQ:ENTA) jumped $8.48 (29%) to $38.14 on Tuesday after AbbVie Inc. (NYSE:ABBV) reported the second set of Phase III data for the pharma's all-oral regimen of three antivirals -- ABT-450 boosted with AbbVie's Norvir ritonavir, ABT-267 and ABT-333 -- plus ribavirin for 12 weeks to treat chronic HCV genotype 1 infection. ABT-450 is the lead HCV protease inhibitor discovered by Enanta and Abbott Laboratories (NYSE:ABT), which spun out its pharmaceutical business into AbbVie. Enanta would be eligible for up to $195 million in milestones if ABT-450 is the first protease inhibitor under the deal to be approved, plus double-digit royalties. ABT-450 is an HCV NS3/4A protease inhibitor.
In 297 patients in the active treatment arm in the Phase III SAPPHIRE-II (Study M13-098) trial, the triple combination regimen produced a sustained virologic response (SVR) 12 weeks after the end of treatment in 96% of patients. SVR12 rates were 96% in patients with HCV genotype 1a infection (n=173) and 97% in patients with HCV genotype 1b infection (n=123). The double-blind trial enrolled 394 patients with chronic HCV genotype 1 infection with no evidence of liver cirrhosis who had failed peginterferon and ribavirin.
SAPPHIRE-II is the second of six trials in AbbVie's Phase III program evaluating the triple combination regimen with and without ribavirin in more than 2,300 treatment-naïve and treatment-experienced patients with HCV genotype 1 infection. Last month, AbbVie reported data from the SAPPHIRE-I trial showing the regimen led to an SVR12 in 96% of treatment-naïve patients in the active treatment arm. AbbVie said it plans to report data from the remaining trials in the "coming months," with regulatory submissions slated to start in 2Q14 (see BioCentury Extra, Nov. 18).
In May, FDA granted breakthrough therapy designation for the triple combination therapy with and without ribavirin to treat HCV genotype 1 infection. ABT-267 is an HCV NS5A protein inhibitor, and ABT-333 is a non-nucleoside HCV NS5B polymerase inhibitor.
FDA reviewers said the potential benefits of dapagliflozin from Bristol-Myers Squibb Co. (NYSE:BMY) to treat Type II diabetes must be weighed against "credible safety concerns," including a possible increased risk of bladder cancer and uncertainty about the CV risk. There were 10 cases of bladder cancer in 5,936 (0.17%) patients treated with dapagliflozin vs. one case in 3,403 (0.03%) patients treated with placebo. In its original 2011 NDA, Bristol-Myers reported nine cases of bladder cancer. The pharma received a complete response letter from FDA in January 2012 in which FDA requested additional data to assess the cancer and CV risks of the sodium-glucose cotransporter 2 (SGLT2) inhibitor.
The reviewers said an updated meta-analysis of major cardiovascular events in the pool of 21 Phase IIb and Phase III trials for dapagliflozin rule out an unacceptable increase in CV risk with a HR of 0.81 (95% CI: 0.59, 1.09) -- well within the threshold required for diabetes drugs. However, the reviewers noted that there "appears to be a numeric imbalance" in early major cardiovascular events (MACE) not favoring the drug. The comments came in briefing documents released ahead of Thursday's meeting of FDA's Endocrinologic and Metabolic Drugs Advisory Committee to discuss the resubmitted NDA for dapagliflozin.
A meta-analysis submitted in the original NDA showed minimal CV risk for dapagliflozin with a HR of 0.67 (95% CI: 0.38, 1.18), but the FDA reviewers revealed that an updated analysis submitted just before the compound's original PDUFA date in October 2011 showed a numerical increase in the HR to 0.82 (95% CI: 0.59, 1.14). As a result, the reviewers said FDA concluded it could not include any suggested CV benefit observed in the original analysis in the benefit-risk profile of the compound. This lack of CV benefit coupled with the cancer risk triggered the agency's complete response letter.
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.
FDA reviewers provided a summary of the efficacy and safety data for Grastek grass Allergy Immunotherapy Tablet (AIT) (MK-7243) from Merck & Co. Inc. (NYSE:MRK), but the reviewers did not take a position on approval of the product. Merck is seeking approval of Grastek to treat Timothy grass pollen induced allergic rhinitis, with or without conjunctivitis, in individuals five years of age and older. The summary came in briefing documents released ahead of Thursday's meeting of FDA's Allergenic Products Advisory Committee to discuss a BLA for the tablet-based sublingual allergen immunotherapy. The PDUFA date is Jan. 25.
Merck has exclusive North American rights to develop and commercialize grass AIT from ALK-Abello A/S (CSE:ALK-B), which markets the product as Grazax in Europe. ALK-Abello was up DKK19 to DKK607 on Tuesday.
On Wednesday, the advisory committee is also scheduled to discuss a BLA from Stallergenes S.A. (Euronext:GENP) for Oralair to treat grass pollen-induced allergic rhinoconjunctivitis (see BioCentury Extra, Dec. 9).
Spectrum Pharmaceuticals Inc. (NASDAQ:SPPI) submitted an NDA to FDA seeking accelerated approval for belinostat to treat relapsed or refractory peripheral T cell lymphoma (PTCL). The company requested Priority Review. The application is based on data from the open-label Phase II BELIEF (PXD101-CLN-19) trial, in which once-daily IV belinostat met the primary endpoint of an objective response rate (ORR) of 20% or greater in 129 patients with relapsed or refractory PTCL (see BioCentury Extra, March 5).
Partner Topotarget A/S (CSE:TOPO) is eligible to receive a $10 million milestone and 1 million Spectrum shares on FDA acceptance of the NDA for belinostat. The company is also eligible for a $24 million milestone upon FDA approval. Spectrum has rights from Topotarget to co-develop and commercialize the small molecule histone deacetylase (HDAC) inhibitor in North America and India.
Spectrum was off $0.02 to $9.39 on Tuesday. Topotarget was up DKK0.07 to DKK3.42 on the day. The company is now above its close of DKK2.94 on Aug. 7, the day before Topotarget shed DKK0.37 (13%) to DKK2.57 after saying it expected to report a loss in 2013 instead of a profit on the year due to a delay in an NDA submission for belinostat (see BioCentury Extra, Aug. 8).
Baxter International Inc. (NYSE:BAX) submitted a BLA to FDA for OBI-1 to treat acquired hemophilia A. Baxter gained the recombinant porcine Factor VIII earlier this year from Ipsen Group (Euronext:IPN; Pink:IPSEY) and Inspiration Biopharmaceuticals Inc., which filed for Chapter 11 bankruptcy in October 2012 (see BioCentury Extra, Jan. 24).
James Vincent, former chairman and CEO of Biogen Inc., passed away Thursday due to complications from liver disease. He was 73 years old. Vincent was CEO of Biogen for more than a decade and was chairman until 2002. Biogen merged with Idec Pharmaceuticals Corp. to form Biogen Idec Inc. (NASDAQ:BIIB) in 2003.
Ambit Biosciences Corp. (NASDAQ:AMBI) presented data at the American Society of Hematology meeting from a Phase IIb trial evaluating the company's quizartinib (AC220) to treat relapsed or refractory FMS-like tyrosine kinase 3 (FLT3; CD135)-internal tandem duplication (ITD)-positive acute myelogenous leukemia (AML). In the trial, continuous treatment with once-daily 30 and 60 mg oral quizartinib in 28-day cycles each led to a composite complete remission rate (CRc) rate, a co-primary endpoint, of 47%. CRc was defined as a sum of complete remission (CR), CR with incomplete platelet recovery and CR with incomplete hematologic recovery. The rates of grade 2 or greater Fridericia's corrected QT (QTcF) interval prolongation -- the other co-primary endpoint -- were 11% in the low-dose arm and 17% in the high-dose arm. The open-label, international trial enrolled 76 patients with FLT3-ITD-positive AML who relapsed or are refractory to second-line salvage therapy or who relapsed after hematopoietic stem cell transplantation (HSCT).
Early next year, Ambit plans to start a Phase III trial with quizartinib, an oral small molecule FLT3 inhibitor, in FLT3-ITD-positive AML patients in first relapse. The company also said it is planning Phase III trials in newly diagnosed AML patients, but could not be reached for details. In September, Astellas Pharma Inc. (Tokyo:4503) and Ambit terminated a 2009 deal to develop and commercialize FLT3 inhibitors, including quizartinib (see BioCentury Extra, March 12).
Ambit closed off $0.11 to $8.20 on Tuesday, just above its IPO price of $8. In May, the company raised $65 million through the sale of 8.1 million shares at $8 in the offering.
Incyte Corp. (NASDAQ:INCY) said oral INCB39110 led to "meaningful improvements" in myelofibrosis-related symptoms, including symptoms associated with splenomegaly, in a Phase II trial to treat intermediate or high-risk primary MF, post-polycythemia vera MF (PPV-MF) and post-essential thrombocythemia MF (PET-MF). The proportion of patients who achieved a 50% or greater improvement in total symptom score (TSS) from baseline to week 12, the primary endpoint, was 22.2% at the twice-daily 100 mg INCB39110 dose, 34.9% at the twice-daily 200 mg dose and 50% at the once-daily 600 mg dose. Median changes in spleen volume from baseline to week 12 were a 5% increase for low-dose INCB39110, a 14.1% reduction for mid-dose INCB39110 and a 9.9% reduction for high-dose INCB39110. The company presented data from the 87-patient, open-label trial at the American Society of Hematology meeting.
Incyte said the data suggest that Janus kinase-1 (JAK-1) inhibition may result in less myelosuppression compared to JAK-1/JAK-2 inhibitors and JAK-2 inhibitors. INCB39110 is a JAK-1 inhibitor. Incyte already markets Jakavi ruxolitinib, an oral JAK-1 and JAK-2 inhibitor, for MF.
INCB39110 is also in Phase II testing to treat psoriasis and rheumatoid arthritis. The company said it plans to develop INCB39110 to treat solid tumors and will initially evaluate combinations that may not be as well tolerated with a JAK-1/JAK-2 inhibitor. Incyte could not be reached for details or its plans for the compound in MF, psoriasis or RA.
On Tuesday, Incyte was up $1.67 to $47.82.
Avanir Pharmaceuticals Inc. (NASDAQ:AVNR) said twice-daily AVP-923 missed the primary endpoint of reducing pain scores from baseline to week 12 vs. placebo in the Phase II PRIME trial to treat central neuropathic pain in multiple sclerosis (MS) patients. Avanir attributed the miss to a high placebo response, and said it will review the PRIME data to determine next steps for AVP-923 in neuropathic pain.
AVP-923 is a combination of dextromethorphan, an NMDA receptor antagonist, and quinidine sulfate, a cytochrome P450 2D6 enzyme inhibitor. Avanir already markets a 20/10 mg dose of the product as Nuedexta in the U.S. to treat pseudobulbar affect (PBA), which is characterized by involuntary episodes of laughing and/or crying.
Avanir reported the clinical news after market close on Tuesday, along with its 4Q financial results for its fiscal year ending Sept. 30. The company was off $0.11 to $4.29 on the day. In early after-hours trading, Avanir fell $0.59 (14%) to $3.70.
Teva Pharmaceutical Industries Ltd. (NYSE:TEVA) on Tuesday introduced two sets of 2014 financial guidance -- one assuming no U.S. generic competition during the year for Copaxone glatiramer acetate and the other accounting for the launch of at least two generic competitors for the company's multiple sclerosis drug. If there is no generic competition for Copaxone during the year, Teva said it expects 2014 non-GAAP diluted EPS of $4.80-$5.10 on net revenues of $19.8-$20.8 billion. If two generics are launched on June 1, Teva said it expects 2014 EPS of $4.20-$4.50 on net revenues of $19.3-$20.3 billion. The Street is expecting 2014 EPS of $4.94 on full-year revenues of $20 billion.
In November, U.S. Supreme Court Chief Justice John Roberts denied Teva's request to stay an appeals court ruling ending exclusivity for Copaxone on May 24, 2014. Teva had requested the stay while it appeals to the Supreme Court a July ruling by the U.S. Court of Appeals for the Federal Circuit that invalidated a process patent held by Teva that was set to expire on Sept. 1, 2015. Teva recorded U.S. Copaxone sales of $2.4 billion for the nine months ended Sept. 30 (see BioCentury Extra, Nov. 15).
In October, former President and CEO Jeremy Levin abruptly departed from Teva due to disagreement over an unspecified aspect of implementing a strategy to put the ailing generics and specialty pharmaceuticals company back on a growth trajectory (see BioCentury, Nov. 4).
Teva was up $0.88 to $41.03 on Tuesday.
Genetic diagnostics company Invitae Corp. (San Francisco, Calif.) raised $40 million in a series E round. Investors in the round include cancer diagnostic company Genomic Health Inc. (NASDAQ:GHDX) and Invitae co-founder, Chairman and CEO Randy Scott. Scott is also co-founder and former CEO and chairman of Genomic Health. Other investors in the E round include existing investors Thomas McNerney & Partners and Genesys Capital Partners, along with new investors Redmile Group and Casdin Capital.
Last year, Genomic Health created Invitae as a subsidiary to commercialize testing services for genetic conditions. The company subsequently merged the subsidiary with fellow genetic testing company Locus Development Inc. to create a standalone company. Scott was a director of Locus, in which Genomic Health and Thomas McNerney had also invested.
Invitae offers full-gene sequencing and testing for a range of disorders and genes, including the breast cancer 1 early onset (BRCA1) and BRCA2 genes. The company has a CLIA-certified laboratory that performs full-gene sequencing and deletion and duplication analysis using next-generation sequencing technology.
Cancer company TetraLogic Pharmaceuticals Corp. (Malvern, Pa.) amended its IPO and said it now plans to sell 6.5 million shares at $7. At the $7 price, the company would raise $45.5 million and be valued at $143.3 million. 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 Securities; 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.
Due to inclement weather, the U.S. Federal Trade Commission postponed a one-day workshop scheduled for Tuesday to examine how state regulations and international naming conventions could affect the development of and competition for biosimilars. The FTC could not be reached in time for publication regarding a rescheduled date for the meeting (see BioCentury Extra, Nov. 11).
Due to inclement weather, FDA postponed a public meeting that was scheduled for Tuesday to discuss fibromyalgia syndrome. The meeting is being held under FDA's Patient-Focused Drug Development initiative, under which the agency is holding public meetings for 20 diseases to discuss the impact of the disease, the measures of benefit that matter most to patients and the adequacy of existing treatment options. FDA said it has not yet rescheduled the meeting (see BioCentury, Sept. 30).
FDA reviewers did not provide a recommendation on the benefit-risk profile of Oralair from Stallergenes S.A. (Euronext:GENP) to treat grass pollen-induced allergic rhinoconjunctivitis. Monday's BioCentury Extra incorrectly attributed the comments to the agency's reviewers.