FDA reviewers said Entyvio vedolizumab from the Millennium Pharmaceuticals Inc. subsidiary of Takeda Pharmaceutical Co. Ltd. (Tokyo:4502) is effective for moderately to severely active ulcerative colitis (UC) and Crohn's disease but said if approved the product may require postmarket risk management beyond labeling due to a potential risk of progressive multifocal leukoencephalopathy (PML). The reviewers highlighted the PML risk with Tysabri natalizumab from Biogen Idec Inc. (NASDAQ:BIIB), which is also an integrin antagonist with a similar mechanism of action to vedolizumab. In its briefing documents, Takeda noted that vedolizumab and Tysabri bind to integrin alpha(4)beta(7) differently. There were no reported cases of PML in the clinical development program for vedolizumab, but FDA reviewers questioned whether vedolizumab's safety database provides an "acceptable pre-marketing assessment" of the PML risk.
Vedolizumab met the primary endpoint in four of five Phase III trials evaluating the compound for induction and maintenance of UC and Crohn's disease. The reviewers said the "key" efficacy question is whether there is "substantial evidence of efficacy" that vedolizumab induces clinical remission in Crohn's disease patients, as one of the two induction trials in the indication missed the primary endpoint. The comments came in documents posted ahead of Monday's joint meeting of FDA's Gastrointestinal Drugs and Drug Safety and Risk Management Advisory Committees to discuss the humanized mAb against integrin alpha(4)beta(7).
For both UC and Crohn's, Takeda is seeking approval of vedolizumab for patients who have had an inadequate response to, have lost response to or were intolerant to either conventional therapy -- including steroids and immunosuppressants -- or anti-tumor necrosis factor (TNF) alpha therapy. Given the potential PML risk, FDA is asking the committee to discuss limiting the population further.
Takeda had originally submitted a single BLA to FDA for vedolizumab, 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.
Forest Laboratories Inc. (NYSE:FRX) raised $1.2 billion in a bumped-up offering of 5% senior unsecured notes due 2021 to institutional investors. On Monday, the company said it planned to raise $1 billion in the note offering and also unveiled a restructuring and new share repurchase program (see BioCentury Extra, Dec. 2).
Forest, which announced the news after market close, was off $0.52 to $55.75 on Thursday.
Celldex Therapeutics Inc. (NASDAQ:CLDX) raised $171.5 million through the sale of 7 million shares at $24.50 in a follow-on underwritten by Jefferies; Leerink; Guggenheim Securities; Oppenheimer; Wedbush PacGrow; Brean Capital; Cantor Fitzgerald; and Roth Capital Partners. Celldex proposed to sell 6.5 million shares in the offering late Tuesday, when its share price was $27.14. The company was off $1.05 to $25.11 on Thursday.
Celldex's rindopepimut (CDX-110) -- a vaccine targeting EGFR variant III (EGFRvIII) -- is in the Phase III ACT IV trial to treat newly diagnosed, surgically resected, EGFRvIII-positive glioblastoma, with data expected in late 2015 or early 2016. The company's glembatumumab vedotin (CDX-011) is in the Phase II METRIC trial in patients with triple-negative breast cancer that over-expresses glycoprotein NMB (GPNMB). The compound is a human mAb against GPNMB linked to the tubulin inhibitor monomethyl auristatin E (MMAE).
Actelion Ltd. (SIX:ATLN) said its board approved the repurchase of up to 10 million shares, or about 8.3%, of the company's common stock over the next three years. Actelion said it will finance the program with cash on hand. As of Sept. 30, the company had CHF1.4 billion ($1.5 billion) in cash, including restricted cash. Actelion was up CHF0.50 to CHF 72.50 on Thursday.
Puma Biotechnology Inc. (NYSE:PBYI) jumped $31.49 (68%) to $77.70 on Thursday after reporting late Wednesday that a regimen containing the company's neratinib "graduated" from the open-label I-SPY 2 trial based on having a high probability of success in patients with HER2-positive/hormone receptor-negative breast cancer in a Phase III trial. The company said that as far as it knows, the neratinib-containing regimen is the first to graduate from I-SPY 2, which is designed to rapidly and inexpensively develop data to support small Phase III trials of new neoadjuvant therapies for locally advanced breast cancer or to help companies quickly kill ineffective candidates. Earlier this year, Puma began a Phase III trial of neratinib in third-line breast cancer. The company has exclusive, worldwide rights to develop and commercialize the oral inhibitor of HER1, HER2 and HER4 kinases from Pfizer Inc. (NYSE:PFE) (see BioCentury Extra, Dec. 4).
The U.K.'s NICE said it is "minded not to recommend" multiple sclerosis drug Lemtrada alemtuzumab from the Genzyme Corp. unit of Sanofi (Euronext:SAN; NYSE:SNY) but the institute said it needs more information before it can make a final recommendation. According to draft guidance, NICE requested "further clarification and analyses," including the costs associated with adverse events and for other MS drugs after Lemtrada failure as well as an economic model that accounts for the sustained accumulation of disability. Comments and the requested information are due Jan. 9.
In September, the European Commission approved Lemtrada to treat relapsing remitting MS (RRMS) in patients with active disease defined by clinical or imaging features. An sBLA for the humanized mAb against CD52 is under review in the U.S. for relapsing MS, with a decision expected late this year (see BioCentury Extra, Nov. 13).
Newron Pharmaceuticals S.p.A. (SIX:NWRN) and partner Zambon Co. S.p.A. (Bresso, Italy) said Zambon submitted an MAA to EMA for safinamide to treat Parkinson's disease (PD). The MAA covers safinamide as add-on therapy to a stable dose of a dopamine agonist for patients with early PD; and as add-on therapy to levodopa alone or in combination with other treatments in patients with mid- to late-stage PD.
Zambon has exclusive rights from Newron to develop and commercialize safinamide worldwide, excluding Asian territories where Meiji Seika Pharma Co. Ltd. (Tokyo, Japan) has rights. The product is an alpha-aminoamide derivative that acts as a reversible monoamine oxidase B (MAO-B) and dopamine reuptake inhibitor while reducing glutamatergic activity.
Newron was unchanged at CHF17.40 on Thursday. The submission news came after market close in Switzerland.
Germany's Federal Joint Committee (G-BA) said in a final benefit assessment that HIV drug Stribild from Gilead Sciences Inc. (NASDAQ:GILD) has "no additional benefit" over Atripla emtricitabine/tenofovir/efavirenz, a comparator requested by G-BA, in therapy-naïve patients. In a September preliminary assessment, Germany's Institute for Quality and Efficiency in Healthcare (IQWiG) had said Stribild was worse than Atripla because it was associated with more AIDS-defining events and serious side effects. G-BA said the overall incidence of AIDS-defining events in the Stribild group was low and that Stribild led to significant improvements in immune deficiency (see BioCentury Extra, Sept. 17).
Drugs that do not have an additional benefit are added to the reference pricing system, which gives a similar base price to therapeutically comparable drugs. If there is no reference, companies negotiate a price no higher than that of the lowest-cost alternative in the indication.
The European Commission approved Stribild in May. The once-daily tablet comprising elvitegravir, cobicistat and Gilead's Truvada emtricitabine/tenofovir is also approved in the U.S. Gilead and Bristol-Myers Squibb Co. (NYSE:BMY) co-market Atripla, a once-daily combination tablet of Truvada and Bristol-Myers' Sustiva efavirenz. Gilead was up $0.72 to $73.19 on Thursday.
Eli Lilly and Co. (NYSE:LLY) discontinued development of edivoxetine (LY2216684) as adjunctive treatment for major depressive disorder (MDD) after once-daily oral edivoxetine as an add-on to a selective serotonin reuptake inhibitor (SSRI) missed the primary endpoint in all three Phase III trials in the indication. The trials -- LNBM, LNBQ and LNBR -- were evaluating edivoxetine in about 3,315 patients with MDD who only achieved a partial response to treatment with an SSRI. Lilly said the discontinuation of edivoxetine as adjunctive treatment for MDD will result in a 4Q13 R&D charge of about $15 million. The pharma is still evaluating the selective norepinephrine reuptake inhibitor in the Phase II/III LNDH trial to treat pediatric ADHD, which is expected to be completed in 2015.
Shire plc (LSE:SHP; NASDAQ:SHPG) reported data on Thursday from the 718-patient Phase III OPUS-2 trial evaluating twice-daily 5% lifitegrast (SAR 1118) to treat dry eye disease. Lifitegrast met the co-primary endpoint of improving patient-reported eye dryness scores from baseline to week 12 vs. placebo (p<0.0001), but missed the co-primary endpoint of improving inferior corneal staining scores from baseline to week 12 vs. placebo (p=0.6186).
Shire gained lifitegrast -- an eye drop formulation of a small molecule integrin beta(2) (LFA-1; MAC-1; CD18) antagonist -- through its April acquisition of SARcode Bioscience Inc. (see BioCentury, April 1).
Last year, SARcode reported that lifitegrast met one co-primary endpoint but missed another co-primary endpoint in the Phase III OPUS-1 trial for dry eye disease. Shire said it will examine data from both trials and discuss the lifitegrast program with FDA to determine next steps. In January, SARcode had said it planned to submit an NDA to FDA for lifitegrast to treat dry eye disease in 2H14.
Shire reported the data after market close on Thursday. The company was up 53p to 2,707p. On NASDAQ, the stock was up $1.10 to $133.12.
Receptos Inc. (NASDAQ:RCPT) jumped $4.94 (22%) to $27.64 on Thursday after announcing that a DMC recommended continuing the Phase II portion and starting the Phase III portion of the Phase II/III RADIANCE trial, which is evaluating RPC1063 to treat relapsing multiple sclerosis (MS). By next quarter, Receptos plans to start the Phase III portion, which will compare RPC1063 vs. interferon beta-1a in about 1,200 patients. Top-line data from the Phase II portion are expected in mid-2014. RPC1063 is a selective sphingosine-1-phosphate receptor 1 (S1PR1; S1P1; EDG1) agonist.
The U.S. House of Representatives voted 325-91 to pass a bill that would make a number of changes to patent-related litigation in an effort to deter patent trolls. The Innovation Act (H.R. 3309) would amend language in the Leahy-Smith America Invents Act (AIA) -- which switched patent priority in the U.S. to first-to-file from first-to-invent -- covering the arguments a party can use to challenge a patent in court. Currently, a party cannot file suit based on earlier legal arguments used with the PTO or on any arguments that it "reasonably could have raised" with PTO but didn't. The Innovation Act would strike the latter language. The bill also would allow judges to require the losing party in a patent suit to pay the legal fees for the other party, and, if the losing party cannot pay, to order other parties with a financial stake in the lawsuit to pay the fees.
Interest groups including the Biotechnology Industry Organization (BIO) have expressed opposition to the bill. In a November letter to the House Judiciary Committee, BIO said some provisions of the bill would create "unreasonable barriers to access to justice" for biotechs with legitimate patent rights. The trade group said the "loser pays" provision would allow parties to add additional parties to a patent suit with "overly broad criteria," and said the bill's increased requirements for an initial infringement complaint would require "unreasonable" disclosure of patent ownership and business information. A group of higher education associations added that the "extremely broad fee-shifting provisions" are a "massive financial risk for universities and their licensees."
The Innovation Act now goes to a Senate committee.
The VP of the European Court of Justice annulled an interim order that prevented EMA from releasing documents in connection to two ongoing suits against EMA challenging the agency's decision to grant access to raw, patient-level data. AbbVie Inc. (NYSE:ABBV) and InterMune Inc. (NASDAQ:ITMN) separately filed suits against EMA earlier this year in response to requests to the agency for data contained in undisclosed MAAs from the companies. In April the European Union General Court ordered EMA to withhold the data. EMA appealed the April order, but despite the annulment the agency said it will not yet release the requested documents. The agency said it does not have timing on when the AbbVie and InterMune suits will be heard by the General Court.
In the interim order, the General Court had said the companies would likely suffer "serious and irreparable damage" if the information was prematurely released. The European Court of Justice said to determine the likelihood of irreparable harm, the lower court needs to assess the clinical and non-clinical information alleged to be confidential (see BioCentury Extra, April 30).
Under its transparency policy, EMA is planning to make summary data publicly available with no restrictions starting Jan. 1, 2014, with controlled access to de-identified patient-level data slated to start Jan. 1, 2015. The agency has said it may delay the implementation (see BioCentury Extra, Nov. 13).
AbbVie was up $0.09 to $49.76 on Thursday. InterMune was off $0.42 to $13.45. The companies could not be reached for comment.
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