FDA granted full approval to Imbruvica ibrutinib from Pharmacyclics Inc. (NASDAQ:PCYC) and Johnson & Johnson (NYSE:JNJ) as first-line therapy for chronic lymphocytic leukemia (CLL) in patients with 17p deletion and to treat CLL in patients who have received at least one prior therapy. FDA granted accelerated approval to the drug for the latter indication in February. The full approvals -- which trigger $60 million in milestone payments to Pharmacyclics from J&J -- came over two months ahead of the Oct. 7 PDUFA date. Pharmacyclics said Imbruvica is the first drug approved specifically for the 17p deletion population, and estimated that 3-7% of de novo patients have 17p deletion at diagnosis and an additional 30-40% of patients may have acquired the deletion during the course of disease. The Bruton's tyrosine kinase (Btk) inhibitor that covalently binds to cysteine residue 481 is already available in the U.S. at a wholesale acquisition cost (WAC) of $8,200 for a 30-day supply. The median treatment duration was 8.6 months in the Phase III RESONATE (PCYC-1112-CA) trial.
The full approvals were based on data from RESONATE, which was stopped early after an interim analysis in January showed that Imbruvica met the primary endpoint of improving progression-free survival (PFS) vs. IV Arzerra ofatumumab from GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) and Genmab A/S (CSE:GEN; OTCBB:GMXAY) in patients with relapsed or refractory CLL or small lymphocytic leukemia (SLL). Pharmacyclics had been seeking full approval for both CLL and SLL, but said it agreed with FDA to gather a larger SLL sample since the SLL patient population in RESONATE consisted of 18 patients (see BioCentury, Jan. 13).
Imbruvica also has accelerated approval from FDA to treat mantle cell lymphoma (MCL) in patients who have received at least one prior therapy.
Pharmacyclics was up $3.68 to $108.50 on Monday.
Reckitt Benckiser Group plc (LSE:RB) disclosed in its 2Q14 earnings that it plans to spin out Reckitt Benckiser Pharmaceuticals Inc. -- its pharmaceutical business -- with a separate listing on the London Stock Exchange over the next 12 months. Last year, Reckitt said it was exploring strategic options for the business, which had 1H14 revenues of L344 million ($588.4 million) -- down 8% in constant currencies from 1H13.
RB Pharmaceuticals' sole marketed product is Suboxone buprenorphine/naloxone sublingual film to treat opioid dependence. The product was developed using PharmFilm thin film technology from MonoSol Rx LLC (Warren, N.J.). RB is developing a pipeline of addiction products that includes RBP-6000, a once-monthly injectable formulation of buprenorphine that has completed Phase II testing to treat opioid dependence; RBP-6300, an abuse-deterrent tablet formulation of buprenorphine in Phase II testing in the same indication; and naloxone nasal spray, which Reckitt said is in Phase I/III testing for opioid addiction.
Reckitt was up 135p to 5,205p on Monday.
AcelRx Pharmaceuticals Inc. (NASDAQ:ACRX) fell $4.44 (41%) to $6.39 on Monday after receiving a complete response letter from FDA for an NDA for Zalviso sufentanil sublingual tablet system to treat moderate to severe acute pain. According to the company, the agency requested additional information from AcelRx to "ensure proper use" of Zalviso, a pre-programmed, handheld device that delivers a sublingual formulation of sufentanil, a synthetic opioid analgesic.
AcelRx said FDA requested data showing a reduction in the incidence of optical system errors caused by a tamper detection mechanism; modified instructions for use to clarify what should be done when there are missing tablets with the system; and more data to verify Zalviso's shelf life. FDA did not request additional clinical trials. AcelRx said it plans to meet with FDA in the next 30 days and to resubmit the NDA by year end.
Partner Gruenenthal Group (Aachen, Germany) submitted an MAA to EMA for Zalviso this month (see BioCentury Extra, July 7).
Horizon Pharma Inc. (NASDAQ:HZNP) dropped $4.69 (34%) to $9.20 on Monday after disclosing that pharmacy benefit managers CVS Caremark Corp. (NYSE:CVS) and Express Scripts Holding Co. (NASDAQ:ESRX) notified the company that arthritis drugs Duexis ibuprofen/famotidine (HZT-501) and Vimovo naproxen/esomeprazole will no longer be on their formularies and will be placed on their exclusion lists effective January 1, 2015. Horizon, which reported 1Q14 U.S. sales of $34 million for Vimovo and $13.9 million for Duexis, estimates about 20-30% of Duexis and Vimovo prescriptions could be affected.
Horizon said it will "immediately accelerate its patient- and physician-focused commercial model to focus prescriptions through other channels," work with other PBMs and "evaluate price increases." According to the Red Book, the average wholesale price (AWP) of Vimovo increased 597% on Jan. 1, 2014, and the AWP of Duexis has gone up 473% since launch in 2011. Each drug has a wholesale acquisition cost (WAC) of $799.20 for a 30-day supply.
Duexis is a fixed-dose combination of 800 mg ibuprofen and 26.6 mg famotidine, a histamine H2 receptor (HRH2; H2R) antagonist. Vimovo is a fixed-dose combination of 500 mg esomeprazole, a proton pump inhibitor (PPI), plus 20 mg naproxen. In 2013, Horizon acquired U.S. rights to Vimovo from AstraZeneca plc (LSE:AZN; NYSE:AZN), which retained ex-U.S. rights and is partnered to develop and commercialize the product with Pozen Inc. (NASDAQ:POZN) under a 2006 deal. Pozen was off $0.93 (12%) to $6.93.
AstraZeneca plc (LSE:AZN; NYSE:AZN) announced a pair of deals on Monday to develop companion diagnostics that can detect non-small cell lung cancer (NSCLC) EGFR mutations directly from circulating tumor DNA in plasma samples. Under one deal, Qiagen N.V. (Xetra:QIA; NASDAQ:QGEN) will develop a test that detects 21 EGFR mutations to identify patients that could benefit from AZ's NSCLC drug Iressa gefitinib, a small molecule EGFR tyrosine kinase inhibitor (TKI). The collaboration is an extension of an agreement the companies signed last year.
Under a separate deal, the Roche Molecular Diagnostics unit of Roche (SIX:ROG; OTCQX:RHHBY) will develop a test for AZD9291, an oral irreversible inhibitor of EGFR-activating mutations and the T790M EGFR resistance mutation. The compound is in Phase I/II testing for metastatic EGFR T790M mutation-positive NSCLC that has progressed following treatment with an EGFR TKI. The Roche deal is part of a broad 2012 agreement between the pharmas to develop companion diagnostics for AZ's products (see BioCentury Extra, Sept. 26, 2012).
Both Qiagen and Roche already market tests to detect EGFR mutations in NSCLC patients. Both tests -- Roche's cobas EGFR Mutation Test and Qiagen's therascreen EGFR Mutation Detection Kit RGQ -- require solid tissue biopsies. Qiagen was up EUR 0.11 to EUR 18.54 and off $0.08 to $24.91 in New York on Monday.
The European Commission approved Envarsus tacrolimus from Veloxis Pharmaceuticals A/S (CSE:VELO) to prevent organ rejection in adult kidney and liver transplant patients. Veloxis said partner Chiesi Farmaceutici S.p.A. (Parma, Italy) plans to launch the product -- a once-daily tablet formulation of tacrolimus delivered with Veloxis' MeltDose technology -- in the EU late this year. Envarsus is also under FDA review to prevent organ rejection in kidney transplant patients, with an Oct. 30 PDUFA date.
Veloxis was up DKK0.05 to DKK2.04 on Monday.
Boehringer Ingelheim GmbH (Ingelheim, Germany) and Zealand Pharma A/S (CSE:ZEAL) partnered to discover and develop therapeutic peptide candidates against an undisclosed cardio-metabolic target from Zealand's preclinical portfolio.
Under the nearly five-year deal, Boehringer will be responsible for and fund preclinical and clinical development as well as commercialization, and will have exclusive, worldwide rights to develop and commercialize any resulting products. Zealand retains co-commercialization rights in Scandinavia and is eligible to receive up to EUR 295 million ($396.2 million) in milestones for the first product developed, plus research funding and tiered royalties. The company, which expects payments of EUR 5.6 million ($7.5 million) in 2014, is also eligible for additional undisclosed milestones for subsequent compounds developed. Zealand was up DKK4.50 to DKK72 on Monday.
In 2011, Zealand granted Boehringer exclusive, worldwide rights to dual agonists of glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R; GLP1R) (see BioCentury Extra, June 16, 2011).
Hospira Inc. (NYSE:HSP) declined to comment on media reports that the company is in talks to acquire the medical nutrition unit of food product conglomerate Danone (Euronext:BN) in a deal valued at about $5 billion. The deal, if completed, would allow Hospira to lower its tax rates by re-domiciling abroad while maintaining a U.S. headquarters. Danone's medical nutrition unit recorded 2013 sales of EUR 1.3 billion ($1.8 billion), and Hospira recorded adjusted net sales of $4.1 billion for the year. Danone, which could not be reached for comment, was up EUR 0.47 to EUR 55.53 on Monday. Hospira was up $0.12 to $51.84 on Monday.
The reports comes amidst a flurry of tax-inversion deals in the industry. Earlier this month, Mylan Inc. (NASDAQ:MYL) announced it would re-domicile in the Netherlands after acquiring the ex-U.S. developed markets branded generics business of Abbott Laboratories (NYSE:ABT). That same week, AbbVie Inc. (NYSE:ABBV) said it would acquire Irish specialty pharma Shire plc (LSE:SHP; NASDAQ:SHPG) and domicile the combined company in the U.K. (see BioCentury, July 21).
Earlier this month, U.S. Treasury Secretary Jacob Lew urged members of Congress to pass legislation to block corporate tax inversions and to make the legislation retroactive to May 2014 (see BioCentury Extra, July 16).
The Wyss Institute for Biologically Inspired Engineering at Harvard University spun out its organs-on-chips technology into newco Emulate Inc. (Cambridge, Mass.), which raised $12 million in a series A round led by NanoDimension. Cedars-Sinai Medical Center and Hansjorg Wyss, the founder of the Wyss Institute, also participated.
Emulate's organs-on-chips, which contain hollow channels lined by living cells, can mimic normal organ physiology as well as model disease. The company said the technology can more quickly and accurately predict human response to medicine than traditional preclinical animal models (see SciBX: Science-Business eXchange, July 22, 2010).
Emulate has developed more than 10 organs-on-chips models and an automated platform that can link organs together to form a human-body-on-chips to replicate body-level responses. Emulate plans to commercialize the platform in the next two years.
Vaccine company PaxVax Inc. (Redwood City, Calif.) secured up to $62 million comprising up to $50 million in debt from Pharmakon Advisors and $12 million in an extension of a series B round from undisclosed existing and new investors. PaxVax used part of the funds to acquire typhoid vaccine Vivotif from Johnson & Johnson (NYSE:JNJ) subsidiary Crucell N.V. and the vaccine's Swiss manufacturing facility.
J&J did not report 2013 sales of Vivotif, an oral typhoid vaccine that contains live, attenuated cells of the bacteria that causes typhoid fever. The vaccine was approved by FDA in 1989 and is approved in 27 countries. PaxVax did not disclose details on the Crucell or debt deals. PaxVax raised $22 million in the B round in December.
Diagnostics company T2 Biosystems Inc. (Lexington, Mass.) amended its IPO on NASDAQ and now plans to sell 4 million shares at $15-$17. At the $16 midpoint, the company would raise $64 million and be valued at $288.4 million. Earlier this month, the company filed to raise up to $69 million. Goldman Sachs; Morgan Stanley; Leerink Partners; and Janney Montgomery Scott are underwriters. In May, T2 Biosystems submitted a 510(k) application to FDA for the company's T2Dx bench-top instrument and its T2Candida assay for use on T2Dx to identify five species of Candida from whole blood samples. T2Candida uses NanoDx magnetic biosensor technology to detect the sepsis-causing pathogens.
The Quark Pharmaceuticals Inc. subsidiary of SBI Biotech Co. Ltd. (Tokyo, Japan) said a single IV dose of QPI-1002 missed the primary endpoint vs. placebo in the Phase II portion of the Phase I/II QRK.006B trial to prevent delayed graft function (DGF) after renal transplantation. Specifically, in 327 evaluable dialysis-dependent patients with end-stage kidney disease, QPI-1002 given 30 minutes after circulatory reperfusion did not lead to at least a 30% relative risk reduction of DGF -- defined as the need for dialysis within the first seven days post-transplant -- vs. placebo. DGF occurred in 30.9% of patients who received QPI-1002 vs. 36.4% for placebo (p=0.349). A post hoc analysis showed QPI-1002 led to an approximate 30% risk reduction of DGF relative to placebo in subgroups of patients who received kidney grafts from donors 35 years of age and older and 45 years of age and older. Data were presented at the World Transplant Conference in San Francisco.
In 2010, Quark granted Novartis AG (NYSE:NVS; SIX:NOVN) an exclusive option to license worldwide rights to QPI-1002. Quark could not be reached for next steps for the product, a short interfering RNA (siRNA) that temporarily inhibits p53 expression.
Targacept Inc. (NASDAQ:TRGT) slid $0.94 (24%) to $3.92 in early after-hours trading on Monday after the company said it was discontinuing development of dexmecamylamine (TC-5214). Targacept said after market close that top-line data from a Phase IIb trial of dexmecamylamine to treat overactive bladder (OAB) "were not compelling enough to justify the compound's continued development." The compound is an S-enantiomer of mecamylamine, a broad spectrum non-competitive nicotinic receptor antagonist.
The news came two weeks after Targacept discontinued development of TC-1734, a neuronal nicotinic acetylcholine receptor alpha(4)beta(2) agonist that was in Phase IIb testing to treat mild to moderate Alzheimer's disease (AD) (see BioCentury Extra, July 14).
Targacept's sole remaining unpartnered compound is TC-6499, a small molecule agonist of nicotinic acetylcholine receptors alpha(3)beta(4) and alpha(4)beta(2) in Phase I/II testing for diabetic gastroparesis. Targacept's AZD1446 is partnered with AstraZeneca plc (LSE:AZN; NYSE:AZN). The neuronal nicotinic acetylcholine receptor alpha(4)beta(2) agonist has completed Phase I testing and is in development for an undisclosed indication. Targacept was unchanged at $3.92 on Monday.
Campbell Alliance's Dealmakers' Intentions Study is the only forward-looking measure of dealmaking activity in the biopharma industry. Now in its sixth year, the study provides insight into what will likely drive the industry's partnering and M&A efforts moving forward -- the results of which were released at last month's BIO International Convention. Download a copy of the full white paper here.