Two appeals courts issued conflicting rulings on whether enrollees on the Affordable Care Act's federal health exchanges are eligible for subsidies -- an issue central to the law's implementation. On Tuesday, the U.S. Court of Appeals for the District of Columbia Circuit voted 2-1 that enrollees on ACA's federal health exchanges are not eligible for subsidies. The court noted the language of ACA makes tax credit subsidies available to individuals enrolled on exchanges "established by the State." The court said ACA "unambiguously restricts" the subsidy to state exchanges and vacated the Internal Revenue Service's regulation that makes enrollees of both federal and state exchanges eligible.
In a separate ruling issued later on Tuesday, the Fourth U.S. Circuit Court of Appeals voted 3-0 that federal enrollees are eligible for subsidies. The court said the statute language is "ambiguous and subject to multiple interpretations" and upheld the IRS regulation "as a permissible exercise of the agency's discretion."
There are federal exchanges in 36 states. According to a June HHS report, more than 5.4 million people have selected a plan on the federal exchanges, 87% of whom receive tax credits.
Emily Pierce, a Department of Justice spokeswoman, said the Obama administration will file a petition asking the D.C. Circuit court to rehear the case en banc. The administration has 45 days to do so. Pierce said that tax credits will remain available to federal and state exchange enrollees in the interim.
If the D.C. Circuit case is upheld, it would essentially gut ACA. Congress could pass legislation to clarify the ambiguous language, but that is unlikely to happen due to the Republican-controlled House of Representatives.
Puma Biotechnology Inc. (NYSE:PBYI) jumped $99.97 (170%) to $159 in early after-hours trading on Tuesday after reporting top-line data for neratinib (PB272) as adjuvant treatment of HER2-positive breast cancer and separately announcing that it will be responsible for more trial costs but will owe lower royalty rates for the compound to partner Pfizer Inc. (NYSE:PFE).
In the Phase III ExteNET trial, extended adjuvant treatment with once-daily oral neratinib (PB272) for one year met the primary endpoint of improving disease-free survival (DFS) at two years vs. placebo (HR=0.67, p=0.0046). The double-blind trial enrolled 2,821 patients with early stage HER2-positive breast cancer who had undergone surgery and adjuvant treatment with Herceptin trastuzumab from Roche (SIX:ROG; OTCQX:RHHBY) and its Genentech Inc. unit. Safety data from the trial are not yet available.
Next half, Puma plans to submit U.S. and EU regulatory applications for neratinib for the extended adjuvant treatment of HER2-positive breast cancer. The oral inhibitor of HER1, HER2 and HER4 kinases will also be included in the Phase III I-SPY 3 trial for the neoadjuvant treatment of breast cancer. The trial is slated to start this year.
Puma and Pfizer amended the 2011 deal under which Puma has exclusive, worldwide rights to neratinib. Puma will now be solely responsible for costs of ongoing trials of the compound initiated by Pfizer. In exchange, the pharma is now eligible for royalties at a fixed rate in the low- to mid-teens. Under the original deal, Puma was responsible for undisclosed expenses for trials, and Pfizer was eligible for 10-20% royalties.
Puma was up $0.05 to $59.03 on Tuesday. If the company's after-hours move holds, Puma will be above its close of $139.92 on Jan. 21, before the company slid after reporting detailed efficacy and safety data for neratinib from the adaptive Phase II I-SPY 2 trial evaluating neoadjuvant breast cancer therapies (see BioCentury Extra, April 8).
Bionor Pharma ASA (OSE:BIONOR) presented data at the International AIDS Society meeting that the company said show for the first time that cancer drug Istodax romidepsin can reactivate latent HIV reservoirs in HIV-infected patients. In six patients with HIV-1 infection in Part A of the open-label, Danish Phase I/II REDUC trial, Istodax -- a histone deacetylase (HDAC) inhibitor from Celgene Corp. (NASDAQ:CELG) -- successfully reactivated HIV transcription. Istodax significantly increased cell-associated unspliced HIV-1 RNA levels from baseline in all six patients (p=0.03). In five patients, Istodax increased plasma HIV-1 RNA levels from undetectable at baseline to quantifiable levels (p=0.035). The patients were all on combination antiretroviral therapy and had undetectable HIV-1 RNA levels at baseline.
Bionor said Istodax is used to "kick" HIV out of latent reservoirs to allow the immune response generated by the company's Vacc-4x to attack and eliminate the infected cells. Vacc-4x is a peptide-based therapeutic vaccine composed of four modified HIV Gag p24 in Phase II testing. Reservoir data from Part B of the REDUC trial are expected next half. Part B is enrolling 20 HIV patients to receive Vacc-4x followed by Istodax for three weeks. Bionor was up NOK0.16 to NOK2.97 on Tuesday.
Celgene -- which markets Istodax in the U.S. to treat peripheral T cell lymphoma and cutaneous T cell lymphoma -- provided Istodax free of charge under a supply deal with Bionor. Celgene was up $1.35 to $86.66 on Tuesday.
A research consortium led by the University of North Carolina is evaluating vorinostat from Merck & Co. Inc. (NYSE:MRK) in a Phase I/II trial to compare HIV RNA expression levels within resting CD4+ T cells of HIV patients. Merck markets the HDAC inhibitor in the U.S. as Zolinza for CTCL.
Synlogic Inc. (Cambridge, Mass.) raised an undisclosed amount in a tranched $29.4 million series A round co-led by existing investor Atlas Venture and new investor New Enterprise Associates. Synlogic is developing engineered microbes that can sense and respond to physiologic conditions, including pH, and then perform an action, such as producing a therapeutic or processing a toxin. The company's pipeline is in preclinical testing for undisclosed indications. Synlogic said it expects to enter the clinic in 18-24 months. NEA's Ed Mathers joined Synlogic's board.
CymaBay Therapeutics Inc. (NASDAQ:CBAY) raised $22 million late Tuesday through the sale of 4 million shares at $5.50 in a follow-on underwritten by Cowen; Stifel; Roth Capital Partners; and National Securities. CymaBay's arhalofenate (MBX-102) is in a Phase IIb trial to treat gout, with data expected in 1H15. The compound is a uricosuric agent.
Last week, CymaBay (formerly Metabolex Inc.) said it planned to sell 3.5 million shares in the offering. In April, the company proposed to raise up to $30 million and said it planned to move its listing to NASDAQ. CymaBay -- which began trading on NASDAQ last month -- became a publicly reporting company via the Form 10 pathway in October and began trading on the OTCQB in January.
The stock was off $0.43 to $5.54 on Tuesday.
Regenerative medicine play Orthocell Ltd. (ASX:OCC) raised A$8 million ($7.5 million) through the sale of 20 million shares at A$0.40 in an IPO on the Australian Stock Exchange. The price values the company at A$33 million ($31 million). Orthocell markets treatments for tendon, cartilage and soft tissue injuries including Ortho-ATI autologous tenocyte implantation therapy that uses a patient's own cells to repair damaged tendons and ligaments. KTM Capital, Azure Capital and Shaw Stockbroking managed the offering. Orthocell's first day of trading is slated for Aug. 8.
Mela Sciences Inc. (NASDAQ:MELA) plans to raise $27.3 million though the sale of about $15 million in senior secured convertible debentures and 12,300 shares of series B convertible preferred stock at $1,000 in a private placement to institutional investors, including Sabby Management; Broadfin Capital; and Great Point Partners. The five-year debentures bear 4% interest and convert into about 5.8 million shares at $2.57. The preferred stock is initially convertible into about 4.8 million common shares at $2.57. Investors will also receive warrants to purchase about 11.2 million common shares at $2.45. H.C. Wainwright is the placement agent.
Mela's MelaFind is approved in the U.S. and has CE Mark approval in the EU to detect early pigmented cutaneous melanoma. The computer-controlled tool identifies lesions to be considered for biopsy using automatic image analysis and statistical pattern recognition from a hand-held device that emits light of multiple wavelengths.
Mela was off $0.33 (12%) to $2.48 on Tuesday.
Actelion Ltd. (SIX:ATLN) reported total sales of CHF993 million ($1.1 billion) in the first half, a 17% increase compared to the same year-ago period. Core EPS rose by 48% in constant currency to CHF3.25. Actelion attributed growth largely to increasing sales of pulmonary arterial hypertension drug Opsumit macitentan, which Actelion launched in the U.S. six months ago and is now covered by most leading insurance companies and formularies in the U.S. The company started marketing the tissue-targeting endothelin receptor antagonist in 10 countries in 1H14 and plans to market the drug in Australia, Italy, France and Spain by the end of 2015. The company also disclosed that it submitted a regulatory filing in Japan in the first half.
Actelion said it will look for acquisitions outside the PAH space to continue its growth trajectory. The company said it now expects full-year core EPS growth to be in the mid-teens, up from its previous guidance of the upper single digits.
Actelion was up CHF2.80 to CHF112.40 on Tuesday.
Philanthropist Ted Stanley committed $650 million to the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard -- the largest ever funding commitment for psychiatric research, according to the institute. With the gift, the center plans to create a comprehensive list of genes with roles in severe psychiatric disorders and identify the biological pathways in which these genes act; develop cellular and animal models that mimic human psychiatric disorders; and identify and develop molecules that modulate biochemical pathways and can serve as drug leads.
Broad timed the announcement of the gift to coincide with publication in Nature of a study by a schizophrenia working group that included institute researchers. The study identified alleles and regions of the genome linked to schizophrenia.
India's Central Drugs Standard Control Organization (CDSCO) has approved 76 trials through May, on pace to top the 107 trials approved in all of 2013. The uptick in trial approvals comes on the heels of reforms enacted to tighten ethical guidelines for conducting trials. In January 2013, after a rash of media reports and subsequent litigation related to trial deaths, India's Supreme Court directed the country's Ministry of Health and Family Welfare (MHFW) to make reforms, including mandating a three-tier approval system to ensure clinical trials meet ethical requirements. At the time, MHFW also issued new regulations on the conduct of trials, including a requirement that trial sponsors provide compensation to patients who suffer injury or death during or as a result of the trial.
Earlier this month, CDSCO released a series of orders designed to clarify the 2013 clinical trial regulations. One order requires that sponsors provide compensation to trial participants "if any drug-related anomaly is discerned at a later stage." Another order specifies that if Indians participate in trials of an NCE for diseases that are "prevalent" in India, the sponsor should seek approval for the NCE in India after approval in the innovator country or in "well-regulated developed country markets."
Vince Suneja, CEO of Indian life science consultancy TwoFour Insight Group LLC, told BioCentury the orders "may cause more questions than answers and may ultimately be detrimental to industry." He noted, for instance, that the CDSCO order on trial compensation does not specify the length of a sponsor's liability. The organization finalized a formula for compensation in June (see BioCentury Extra, June 3).
Seven companies committed to providing access to deprioritized compounds to the U.K.'s Medical Research Council for academic research projects. The council plans to publish a full list of the available compounds this year, and U.K. scientists will be able to apply for MRC funding to conduct their projects.The companies are AstraZeneca plc (LSE:AZN; NYSE:AZN); GlaxoSmithKline plc (LSE:GSK; NYSE:GSK); Eli Lilly and Co. (NYSE:LLY); the Janssen Research & Development LLC unit of Johnson & Johnson (NYSE:JNJ); Pfizer Inc. (NYSE:PFE); Takeda Pharmaceutical Co. Ltd. (Tokyo:4502); and UCB Group (Euronext:UCB).
Earlier this year, AZ partnered with MRC to evaluate over 2 million AstraZeneca molecules under a five-year deal under which the council is funding up to 15 screening projects per year across a range of therapy areas and diseases (see SciBX: Science Business eXchange, April 17).
Advaxis Inc. (NASDAQ:ADXS) and the MedImmune Inc. unit of AstraZeneca plc (LSE:AZN; NYSE:AZN) partnered in a non-exclusive deal to conduct a Phase I/II trial with Advaxis' ADXS-HPV in combination with MedImmune's MEDI4736 to treat HPV-associated cervical cancer and HPV-associated head and neck cancer. Advaxis will fund and conduct the trial, which is slated to begin early 2015. MedImmune has first right of negotiation to develop MEDI4736 and ADXS-HPV combinations. Financial terms are not disclosed.
ADXS-HPV, a live Listeria monocytogenes-based immunotherapy expressing HPV type 16 E7, is in Phase II testing for cervical cancer and Phase I/II testing for HPV-associated head and neck and anal cancer. MEDI4736, a human IgG1 mAb targeting programmed cell death 1 ligand 1 (PD-L1; B7-H1; CD274), is in Phase III testing to treat non-small cell lung cancer (NSCLC).
Advaxis was up $0.12 to $2.82 on Tuesday.