FDA's Gastrointestinal Drugs and Drug Safety and Risk Management advisory committees were unfazed by FDA reviewers' concerns about the potential risk of progressive multifocal leukoencephalopathy (PML) with Entyvio vedolizumab from the Millennium Pharmaceuticals Inc. subsidiary of Takeda Pharmaceutical Co. Ltd. (Tokyo:4502). The panel members unanimously voted that Takeda adequately characterized the risk of PML with vedolizumab, which is under review to treat ulcerative colitis (UC) and Crohn's disease (see BioCentury Extra, Dec. 5).
Of the 21 panel members, 13 voted that the benefits of vedolizumab outweigh the potential risks for UC in patients that have failed steroids, immunosuppressants or anti-TNF alpha therapy, while eight voted that the benefits outweigh the risks for patients who failed immunosuppressants or anti-TNF alpha therapy but not steroids. For the Crohn's indication, 14 panel members voted that the benefits of vedolizumab outweigh the potential risks for patients who have failed steroids, immunosuppressants or anti-TNF alpha therapy, while six voted the benefits outweigh the risks for patients who have failed immunosuppressants or anti-TNF alpha therapy but not steroids. One panel member voted that the benefits did not outweigh the risks for either population of Crohn's disease patients.
Takeda had originally submitted a single BLA to FDA for the humanized mAb against integrin alpha(4)beta(7), but said the agency chose to review the indications under different timelines. The BLA for UC is under Priority Review, with a decision expected by Feb. 18. The BLA for Crohn's disease is under standard review, with a decision expected by June 18.
FDA reviewers said the benefit-risk profile of Oralair from Stallergenes S.A. (Euronext:GENP) supports approval to treat grass pollen-induced allergic rhinoconjunctivitis. The reviewers said the sublingual immunotherapy against five grass allergens showed "consistent, statistically significant, clinically meaningful efficacy" and has a favorable safety profile. The comments came in briefing documents released ahead of Wednesday's meeting of FDA's Allergenic Products Advisory Committee to discuss a BLA for Oralair. Stallergenes is not disclosing when it expects a decision on the application.
On Thursday, the advisory committee is also scheduled to discuss a BLA from Merck & Co. Inc. (NYSE:MRK) for grass Allergy Immunotherapy Tablet (AIT). FDA has not yet released briefing documents for that meeting. Merck has exclusive North American rights to develop and commercialize the tablet-based sublingual allergen immunotherapy from ALK-Abello A/S (CSE:ALK-B), which markets the product as Grazax in Europe.
Stallergenes was off EUR 0.01 to EUR 52.99 on Monday. ALK-Abello was up DKK6 to DKK588.
FDA reviewers said Myalept metreleptin from the Amylin Pharmaceuticals Inc. subsidiary of Bristol-Myers Squibb Co. (NYSE:BMY) is effective in a subgroup of lipodystrophy patients and backed the company's proposed REMS to educate prescribers about the potential risk of developing neutralizing antibodies and lymphoma. The reviewers said metreleptin led to a benefit "unlikely to have been achieved spontaneously" in patients with generalized lipodystrophy with severe insulin resistance resulting in diabetes and/or severe hypertriglyceridemia that is not adequately controlled with other therapies. The BLA is based on 72 patients in two open-label trials sponsored by NIH, as well as 28 patients enrolled in the Bristol-Myers-sponsored FHA101 trial. The reviewers did note that it is "unclear if a subgroup of patients with partial lipodystrophy can be clearly identified" that would benefit from the recombinant form of human leptin.
The reviewers also said there are serious risks with metreleptin, including the risk of T cell lymphoma and neutralizing antibodies. The reviewers backed implementation of a REMS to monitor for development of adverse events. Bristol-Myers has proposed a REMS that would include a physician and pharmacy certification component, as well as a prescriber education program and a metreleptin safety registry.
The comments came in briefing documents posted ahead of Wednesday's meeting of FDA's Endocrinologic and Metabolic Drugs Advisory Committee to discuss metreleptin, which is under Priority Review to treat generalized lipodystrophy and metabolic disorders associated with partial lipodystrophy. The PDUFA date is Feb. 24.
Bristol-Myers folded Amylin's diabetes portfolio, including metreleptin, into its diabetes deal with AstraZeneca plc (LSE:AZN; NYSE:AZN). Amylin has rights to metreleptin from Amgen Inc. (NASDAQ:AMGN) (see BioCentury, July 9, 2012).
Proteostasis Therapeutics Inc. (Cambridge, Mass.) and Biogen Idec Inc. (NASDAQ:BIIB) partnered to develop inhibitors of ubiquitin specific peptidase 14 tRNA-guanine transglycosylase (USP14; TGT) to treat neurodegenerative diseases that involve toxic protein aggregation. Proteostasis will receive an undisclosed upfront payment and an equity investment. The company is also eligible for research support and up to $200 million in milestones, plus tiered royalties. Biogen Idec directed questions on the deal to Proteostasis, which could not be reached for details.
Proteostasis has exclusive rights to technologies related to the ubiquitin-proteasome pathway from Harvard University (see SciBX: Science-Business eXchange, Sept. 30, 2010)
Biogen Idec was off $4.72 to $286.18 on Monday.
FDA accepted for review an NDA from Helsinn Healthcare S.A. (Pazzallo-Lugano, Switzerland) for NEPA to prevent acute and delayed chemotherapy-induced nausea and vomiting (CINV). The PDUFA date is Sept. 26, 2014. The product is a fixed-dose combination of 300 mg netupitant, a neurokinin 1 (NK1) Substance P receptor antagonist, and 0.5 mg palonosetron, a selective serotonin (5-HT3) receptor antagonist. Palonosetron is already marketed in more than 60 countries worldwide to prevent CINV. If approved, Eisai Co. Ltd. (Tokyo:4523) and Helsinn will co-promote NEPA in the U.S.
Celgene Corp. (NASDAQ:CELG) presented additional data at the American Society of Hematology meeting from the Phase III FIRST (MM-020/IFM 07-01) trial evaluating the company's Revlimid lenalidomide to treat patients with newly diagnosed multiple myeloma (MM). In the trial, continuous oral Revlimid plus low-dose dexamethasone until disease progression led to a median progression-free survival (PFS), the primary endpoint, of 25.5 months vs. 21.2 months for a combination of melphalan, prednisone and thalidomide for 72 weeks at a median follow-up of 37 months (HR=0.72, p=0.00006). Additionally, on the secondary overall survival (OS) endpoint, a pre-planned interim analysis at 64% of survival events showed Revlimid until disease progression led to a four-year OS rate of 59.4% vs. 51.4% for melphalan, prednisone and thalidomide (HR=0.78, p=0.0168).
In July, Celgene had reported that Revlimid plus low-dose dexamethasone until disease progression met the primary endpoint in the open-label trial, which enrolled 1,623 patients aged 65 and older with newly diagnosed MM who are ineligible for autologous stem cell transplantation (ASCT). Next quarter, Celgene plans to submit regulatory applications in the U.S. and EU for Revlimid to treat newly diagnosed MM.
The company already markets the thalidomide analog in nearly 70 countries, including the U.S. and EU countries, in combination with dexamethasone to treat relapsed or refractory MM in patients who have received one or more prior therapy. Revlimid is also approved in the U.S. and EU to treat patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) with a 5q chromosomal deletion and in the U.S. for relapsed or refractory mantle cell lymphoma (MCL).
Celgene was up $3.58 to $170.01 on Monday.
Gilead Sciences Inc. (NASDAQ:GILD) presented additional data at the American Society of Hematology meeting showing twice-daily oral idelalisib led to a median overall survival (OS), a secondary endpoint, of 20.3 months in the Phase II Study 101-09 to treat refractory indolent non-Hodgkin's lymphoma (NHL). The company also presented updated data showing idelalisib led to an overall response rate (ORR) of 57% and a median progression-free survival (PFS) of 11 months. In June, Gilead reported interim data from the trial showing idelalisib led to an ORR of 53.6% and median PFS of 11.4 months. The single-arm, open-label, international trial enrolled 125 patients with previously treated indolent NHL that is refractory to both rituximab and to alkylating agent-containing chemotherapy. In September, Gilead submitted an NDA to FDA for the small molecule inhibitor of phosphoinositide 3-kinase (PI3K) delta to treat refractory indolent NHL based on data from Study 101-09.
Gilead also provided a regulatory update on the compound, disclosing that last month EMA accepted for review an MAA for idelalisib to treat indolent NHL and chronic lymphocytic leukemia (CLL). The MAA is under accelerated assessment. Also, Gilead disclosed that FDA granted breakthrough therapy designation for idelalisib to treat relapsed CLL. In October, Gilead stopped early a Phase III trial evaluating idelalisib for CLL after a predefined interim analysis showed idelalisib plus rituximab met the primary endpoint of improving PFS vs. placebo plus rituximab (see BioCentury Extra, Oct. 9).
On Monday, Gilead was up $1.20 to $75.19. Late Friday, FDA approved Gilead's Sovaldi sofosbuvir (GS-7977) for HCV (see BioCentury Extra, Dec. 6).
Biogen Idec Inc. (NASDAQ:BIIB) and the Genentech Inc. unit of Roche (SIX:ROG; OTCQX:RHHBY) co-market rituximab as Rituxan in the U.S. Roche markets it as MabThera elsewhere.
Johnson & Johnson (NYSE:JNJ) disclosed that FDA accepted and granted Priority Review to a BLA for siltuximab (CNTO 328) to treat multicentric Castleman's disease (MCD) in patients who are HIV-negative and human herpes virus 8 (HHV-8)-negative. The PDUFA date is not disclosed. An MAA is also under accelerated assessment by EMA for the indication. The pharma submitted the applications in September. Multicentric Castleman's disease is a rare type of Castleman's disease that affects more than one group of lymph nodes in different anatomical areas. Castleman's disease is a B cell proliferative disorder that is not malignant but is nonetheless fatal because of systemic inflammation.
J&J also presented data at the American Society of Hematology meeting showing that IV siltuximab every three weeks plus best supportive care (BSC) led to a greater durable tumor and symptomatic response rate, the primary endpoint, vs. placebo plus BSC (34% vs. 0%, p=0.0012) in the Phase II MCD2001 trial to treat MCD. Median time to treatment failure was not reached in the siltuximab arm vs. 134 days in the placebo arm. The double-blind, international trial enrolled 79 patients with multicentric Castleman's disease who are HIV-negative and HHV-8-negative. Siltuximab is a chimeric mAb against IL-6.
Intra-Cellular Therapies Inc. (New York, N.Y.) said once-daily 60 mg ITI-007 given in the morning met the primary endpoint of improving Positive and Negative Syndrome Scale (PANSS) total score from baseline to day 28 vs. placebo in the Phase II ITI-007-005 trial to treat acutely exacerbated schizophrenia (p=0.017). A once-daily 120 mg dose of ITI-007 given in the morning missed the primary endpoint. The double-blind, U.S. trial enrolled 335 patients with an acutely exacerbated episode of schizophrenia. Data are slated to be presented on Tuesday at the American College of Neuropsychopharmacology meeting.
Intra-Cellular said it plans to request a meeting with FDA to discuss plans to conduct separate clinical trials with ITI-007 in schizophrenia and bipolar disorder. The company also said it plans to conduct clinical testing of the dual serotonin (5-HT2A) receptor antagonist and dopamine receptor phosphoprotein modulator (DPPM) for behavioral disturbances in dementia and Alzheimer's disease (AD).
Covagen AG (Zurich, Switzerland) secured CHF42 million ($47.1 million) in a tranched series B round led by new investor Gimv. New investor Ascent Biomedical Ventures also participated, along with existing investors Novartis Venture Fund; Edmond de Rothschild Investment Partners; Seroba Kernel Life Sciences; Ventech; and MP Healthcare Venture Management. Covagen can obtain an additional CHF14 million ($15.7 million) if undisclosed milestones are met. The company declined to disclose how much of the funding it has already received. Gimv's Karl Naegler and Ascent's Avi Kometz joined Covagen's board.
Covagen's COVA322 is in preclinical development to treat inflammatory diseases, including rheumatoid arthritis (RA) and psoriatic arthritis. Early next year, the company plans to start Phase I testing of the dual bispecific TNF/IL-17A inhibitor. COVA322 was developed using Covagen's Fynomer protein engineering technology. Fynomers are based on the naturally occurring human protein scaffold Fyn SH3-derived binding protein (see BioCentury, Jan. 25, 2010).
Wound care company Gecko Biomedical S.A.S. (Paris, France) closed EUR 8 million ($11 million) in a series A round co-led by new investors Omnes Capital and CM-CIC Capital Finance. New investor CapDecisif Management also participated. Gecko is developing biodegradable sealants and adhesives based on biocompatible elastomeric polymers for wound closure in minimally invasive surgery. The company plans to start clinical testing of a lead program in 2015. Omnes' Alexia Perouse and CM-CIC's Karine Lignel will join Gecko's board.
NIH Director Francis Collins named Philip Bourne associate director for data science. Bourne will join NIH early next year from the University of California, San Diego, where he is a professor and associate vice chancellor for innovation and industry alliances at the university's Office of Research Affairs. He is also associate director of the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank, which publicly stores macromolecule structural data.
Bourne will replace Eric Green, who has been serving as acting associate director for data science since Collins created the position in January. Green is director of NIH's National Human Genome Research Institute (NHGRI). The agency created the associate director for data science position to lead agency-wide strategic initiatives that "collectively aim to capitalize on the exponential growth of biomedical research data, such as from genomics, imaging, and electronic health records."