Amgen Inc. (NASDAQ:AMGN) filed a lawsuit in the U.S. District Court for the District of Delaware alleging that alirocumab from Sanofi (Euronext:SAN; NYSE:SNY) and Regeneron Pharmaceuticals Inc. (NASDAQ:REGN) infringes three Amgen patents covering monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9).
Amgen is seeking an injunction to prevent Sanofi and Regeneron from manufacturing and selling alirocumab within the U.S. or from importing the human mAb targeting PCSK9 into the U.S. prior to the expiration of Amgen's patents, which have an estimated expiration date of 2029, according to the company's most recent 10K. Amgen also is seeking a ruling that alirocumab infringes its patents and wants monetary damages for any sales ahead of expiration of the patents. The suit also demands a jury trial.
In August, Amgen submitted a BLA to FDA for evolocumab, its human mAb against PCSK9, to treat high cholesterol.
Sanofi and Regeneron have completed Phase III trials of alirocumab to treat hypercholesterolemia. The companies plan to submit a BLA to FDA before year end and intend to use a Priority Review voucher to expedite the review, potentially putting the partners ahead of Amgen in the race to market (see BioCentury, Aug. 4).
The partners paid $67.5 million to obtain the tradable voucher from BioMarin Pharmaceutical Inc. (NASDAQ:BMRN), which gained the voucher upon the approval of Vimizim elosulfase alfa to treat mucopolysaccharidosis IVA (MPS-IVA, Morquio's syndrome) under FDA's Rare Pediatric Disease Review Voucher program.
In its suit, Amgen notes its submission is subject to a standard 10-month review, while Sanofi and Regeneron expects a six-month review.
The patents in question are Nos. 8,563,698; 8,829,165; and 8,859,741.
Amgen was up $3.24 to $133.69 on Friday. Sanofi gained $1.16 to $51.80 in NYSE trading. Regeneron, which also had positive news about its Eylea aflibercept ophthalmic drug, gained $28.93 to $369.64 (see below).
FDA reviewers said "at least some CF patients with a R117H mutation" in the cystic fibrosis transmembrane conductance regulator (CFTR) gene benefit from Kalydeco ivacaftor from Vertex Pharmaceuticals Inc. (NASDAQ:VRTX). However, the reviewers questioned whether there are sufficient data to support approval of Kalydeco for CF patients six years of age and older with the mutation -- the indication for which Vertex is now seeking approval.
The comments came in briefing documents released ahead of next Tuesday's meeting of the Pulmonary-Allergy Drugs Advisory Committee to discuss an sNDA seeking to add the R117H mutation to Kalydeco's label.
Last year, Vertex said Kalydeco missed the primary endpoint of improving the mean absolute change in percent predicted FEV1 from baseline to week 24 vs. placebo in the 69-patient Phase III KONDUCT trial in CF patients six and older with the R117H mutation.
However, in a pre-specified subgroup of patients 18 and older, Kalydeco led to a significant mean absolute improvement of 5% in percent predicted FEV1 from baseline to week 24 vs. placebo. Kalydeco also significantly reduced sweat chloride levels, a secondary endpoint.
In the briefing documents, the reviewers noted the adult CF subpopulation "appeared to demonstrate a positive response" but said patients six to 11 years of age "significantly worsened" on both FEV1 and respiratory symptoms.
The reviewers noted there were no available data for patients 12-17 years of age.
Vertex submitted the sNDA in June originally seeking approval for patients 18 and older with the R117H mutation. In August, Vertex amended the sNDA to include patients six years of age and older.
According to Vertex, there are about 500 CF patients six and older with the mutation in the U.S., of whom about 300 are 18 and older.
Kalydeco, a small molecule potentiator of the CFTR gene, is approved in the U.S. to treat CF patients ages six and older with at least one copy of nine mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R.
Vertex gained $1.09 to $102.35 on Friday.
Astellas Pharma Inc. (Tokyo:4503) and CoMentis Inc. (South San Francisco, Calif.) terminated a 2008 deal to develop and commercialize beta-secretase (BACE1) inhibitors to treat Alzheimer's disease (AD). Astellas, which paid $80 million up front to license rights to the program and paid $20 million for an equity stake in CoMentis, returned all rights to the candidates covered under the deal.
CoMentis General Counsel and VP of Alliance Management Daniel Hunt told BioCentury the program did not achieve any development milestones during the collaboration and declined to disclose which stage of development the program had reached. Astellas did not reply to inquiries.
One candidate covered in the deal, CTS-21166, had already completed a Phase I trial when the deal was struck. The deal included up to $660 million in development milestones, plus commercial milestones and royalties (see BioCentury, May 5, 2008).
In 2013, Astellas partnered with MitoKyne Inc. (Boston, Mass.) to develop compounds targeting mitochondrial function for genetic, metabolic and neurodegenerative disorders as well as aging diseases, including Alzheimer's.
Hunt said CoMentis will continue its BACE1 inhibitor program, though its scope has not yet been determined.
FDA approved expanded labeling for Embeda morphine sulfate/naltrexone hydrochloride extended-release capsules from Pfizer Inc. (NYSE:PFE) to include data from abuse-deterrent studies.
Embeda is indicated to treat pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.
FDA noted the product has properties when crushed and taken orally or intranasally that are expected to reduce abuse, but not completely prevent it. The agency is requiring postmarketing studies to evaluate the effects of Embeda's abuse-deterrent features on abuse of the drug. It also is requiring educational guides for healthcare professionals and patients under its classwide REMS.
Pfizer expects Embeda to be available in the U.S. early next year. It gained the product through its acquisition of King Pharmaceuticals Inc. in 2011.
FDA said Embeda is the third extended-release opioid analgesic to be approved with abuse-deterrent labeling consistent with draft guidance the agency issued last year. Purdue Pharma L.P. (Stamford, Conn.) markets the other two: a reformulation of OxyContin oxycodone and Targiniq ER oxycodone/naloxone.
The European Commission has approved Imbruvica ibrutinib from Pharmacyclics Inc. (NASDAQ:PCYC) and the Janssen-Cilag International NV unit of Johnson & Johnson (NYSE:JNJ) to treat patients with mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).
The European approval triggers a milestone payment of undisclosed size to Pharmacyclics from J&J. The biotech received $60 million in milestones when FDA approved the drug for MCL in November 2013 and for CLL in July 2014.
The indicated populations are adults with relapsed or refractory MCL, adults with CLL who have received at least one prior therapy, or as first line treatment in CLL patients who have chromosome 17p deletion or TP53 mutation and are unsuitable for chemo-immunotherapy.
Imbruvica is a Bruton's tyrosine kinase (Btk) inhibitor that covalently binds to cysteine residue 481. Pharmacyclics reported U.S. sales of $165.7 million in 1H14; it splits U.S. profits evenly with J&J under their co-development agreement. The pharma has commercialization rights outside the U.S.
Pharmacyclics closed up $3.07 to $112.21 on Friday.
The U.K.'s NICE proposed to recommend Glivec imatinib from Novartis AG (NYSE:NVS; SIX:NOVN) as adjuvant treatment for up to three years in adult patients at high-risk for tumor recurrence following complete surgical resection of Kit (CD-117)-positive gastrointestinal stromal tumors (GIST).
The decision reverses NICE's August 2010 opinion, when it cited a lack of clinical evidence to support use of the drug by the National Health Service as an adjuvant treatment after surgical removal of a GIST. At the time, NICE pledged to review new clinical evidence when it became available.
In Friday's final draft guidance, NICE said the positive recommendation was based on additional data from five-year follow-ups of the Phase III SSGXVIII/AIO and ACOSOG Z9001 trials. The committee concluded the evidence showed one year of treatment with Glivec following surgical resection increased recurrence-free survival compared to control, and that three years of treatment was more effective than one year.
NICE recommends a dose of 400 mg per day, which would cost about L20,700 ($33,294) for a one-year course and L62,100 for three years. The appraisal committee concluded the cost per QALY (Quality Adjusted Life Year) was between L3,610 and L12,100 for a year of adjuvant imatinib compared with no adjuvant treatment, and between L16,700 and L30,000 for three-year adjuvant imatinib compared with one year.
Imatinib is a BCR-ABL tyrosine kinase inhibitor approved as Glivec in the EU and Gleevec U.S. to treat multiple cancers.
Canaan Partners promoted Tim Shannon to general partner and Julie Papanek to principal on the healthcare team. Shannon joined Canaan in 2009 after serving as CEO of CuraGen Corp. through its sale to Celldex Therapeutics Inc. (NASDAQ:CLDX). Shannon remains a director at Celldex, holds board seats at Canaan portfolio companies Aldea Pharmaceuticals Inc. (Redwood City, Calif.); Civitas Therpeutics Inc. (Chelsea, Mass.); CytomX Therapeutics Inc. (South San Francisco, Calif.); and Novira Therapeutics Inc. (Radnor, Pa.). Prior to joining Canaan as an associate in August 2013, Papanek worked in marketing, development, and business development at Genentech.
Jump Capital named Garrett Vygantas a partner. Vygantas was the founding CEO of NewBridge Pharmaceuticals Ltd. (Dubai, UAE), and previously an entrepreneur-in-residence and investment director at Burrill & Co.'s Burrill Venture Group.
Regeneron Pharmaceuticals Inc. (NASDAQ:REGN) said top-line data from a comparative effectiveness study using VEGF drugs to treat diabetic macular edema showed its Eylea aflibercept was superior to Avastin bevacizumab and Lucentis ranibizumab from the Genentech Inc. unit of Roche (SIX:ROG; OTCQX:RHHBY).
In the 660-patient NIH-sponsored study, Regeneron said Eylea led to a greater change in best-corrected visual acuity (BCVA) from baseline to 52 weeks compared to Avastin and Lucentis, the primary endpoint. According to its protocol, the study compared intravitreal injections of 2 mg Eylea, 1.25 mg Avastin and 0.5 mg Lucentis to treat central-involved DME in eyes with visual acuity of 20/32 to 20/320.
The rates of most adverse events (AEs) were similar for all three drugs, except for overall CV events, which were higher in the Lucentis group than the Eylea and Avastin groups (p<0.01). Rates of arterial thromboembolic events were 2% in the Eylea group, 4% in the Avastin group and 5% the Lucentis group (p-value undisclosed).
Regeneron declined to provide further comparisons between the trial arms. It said the Diabetic Retinopathy Clinical Research Network (DRCR), which ran the study, will present the detailed data at a future medical conference.
Eylea is a human fusion protein that binds all forms of VEGF-A and placental growth factor (PGF; PlGF). Avastin is a humanized mAb against VEGF, and Lucentis is a humanized mAb fragment. Only Lucentis and Eylea are approved for DME, although Avastin is used off label at the 1.25 mg dose.
Regeneron gained $28.93 to $369.64 on Friday, despite news that Amgen Inc. (NASDAQ:AMGN) filed a patent suit against the company over mAbs against proprotein convertase subtilisin/kexin type 9 (PCSK9) (see Top Story).
Neothetics Inc. (San Diego, Calif.) and PolyPid Ltd. (Petach Tikva, Israel) filed for IPOs on NASDAQ.
Neothetics filed to raise up to $63.3 million with Piper Jaffray; Guggenheim Securities; and Needham as underwriters. Neothetics expects to begin two Phase III trials of LIPO-202, a subcutaneous formulation of salmeterol, in 1H15. It expects top-line data by YE15, with an NDA for the long-acting adrenergic receptor beta 2 agonist (LABA) in 2H16. PolyPid proposed to raise up to $24 million with Aegis Capital; MLV; and Chardon Capital Markets as underwriters. Its lead candidate is BonyPid, a biodegradable bone filler combined with an antibiotic release platform designed to treat long-bone fractures and prevent bone infection. The company plans to begin a confirmatory trial of BonyPid-1000 and a pilot program for dental counterpart BonyPid-500 in 2H15. PolyPid hopes to launch the products in 1H17.
Tetraphase Pharmaceuticals Inc. (NASDAQ:TTPH) climbed $4 (20%) to $24.11 on Friday after announcing it has priced the sale of 3.95 million shares at $19 in a follow-on that is expected to close Oct. 22. The company would raise $75 million at the close of the deal underwritten by BMO Capital Markets; Stifel; Guggenheim Securities; JMP Securities; and Needham.
Tetraphase shares jumped $1.93 (15%) to $15.01 on Sept. 3 after reporting data from the lead-in portion of a Phase III trial of eravacycline to treat complicated urinary tract infection (cUTI). Data for the broad-spectrum fluorocycline antibiotic are expected in mid-2016.
Last year, the company raised $80.6 million in an IPO and $45 million in a follow-on.
President Obama's nomination of Michelle Lee as director of the U.S. Patent and Trademark Office marks a victory of Silicon Valley tech interests over the U.S. biopharmaceutical industry in their battle for control over quotidian decisions on patent policy and influence over legislation, according to congressional staff and pharma industry lobbyists who spoke to BioCentury. But technical regulatory decisions will be closely watched as well.
Last summer, White House officials considered pharmaceutical executive Philip Johnson for the position. Johnson, SVP for intellectual property policy and strategy at Johnson & Johnson (NYSE:JNJ), has represented the Coalition for 21st Century Patent Reform, which includes many pharmaceutical company members.
Tech companies, which been locked in a stalemate with the coalition and biopharmas over patent reform legislation, strongly opposed Johnson.
Drug developers contend that Silicon Valley-backed legislation to crack down on so-called "patent trolls" would erode the IP rights of universities and biopharma companies that hold technology patents long before they are commercialized.
Although the conflict over the top PTO position has focused on legislation, Lee's regulatory activities are likely to be more important to drug developers. She will oversee the PTO's efforts to put into operation two recent Supreme Court rulings on the patentability of products involving natural phenomena and natural products, Association for Molecular Pathology v. Myriad Genetics Inc. and Mayo Collaborative Services v. Prometheus Laboratories Inc. (see BioCentury Extra, Aug. 6).
Kite Pharma Inc. is testing its autologous T cell therapy against CD19 to treat relapsed or refractory acute lymphoblastic leukemia (ALL). The Oct. 13 BioCentury Extra misstated the indication.
Novartis plans to start Phase II testing to treat diffuse large B cell lymphoma in early 2015. The Oct. 15 BioCentury Extra misstated the milestones.
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