Seres Therapeutics Inc. (NASDAQ:MCRB) sank $24.83 (69%) to $10.94 on Friday, shedding nearly $1 billion in market cap, after it said microbiome-based therapy SER-109 missed the primary endpoint in the 89-patient Phase II ECOSPOR study to prevent recurrent Clostridium difficile infection (CDI). SER-109 did not significantly reduce the relative risk of CDI recurrence at up to eight weeks vs. placebo, with CDI recurrence in 44% of patients receiving SER-109 vs. 53% for placebo.
In patients aged 65 and older, CDI recurrence occurred in 45% of patients receiving SER-109 vs. 80% for placebo. In patients younger than 65, the rates were 43% for SER-109 and 27% for placebo. Both subgroup analyses were prespecified.
The most common adverse events in the SER-109 arm were diarrhea, abdominal pain and flatulence, with no drug-related serious adverse events.
In 2014, Seres said SER-109 prevented CDI recurrence within eight weeks in 87% of patients, meeting the primary endpoint of an open-label Phase Ib study.
On a conference call Friday, Seres President and CEO Roger Pomerantz said the results were inconsistent with expectations, with "confounding placebo data." He said the company is collecting data to better understand the results, including patient-level microbiome data before, during and after the study, and said the company is conducting a root-cause analysis.
EVP and CMO Shelley Trucksis said the patient populations were similar in the Phase Ib and II trials. In the Phase Ib study, the criteria for CDI recurrence included diarrhea for three or more consecutive days, while the Phase II study's criteria included diarrhea for two or more consecutive days. Both studies' criteria also included a positive CDI test and the need for antibiotic treatment.
SER-109 is a purified and encapsulated suspension of about 50 species of Firmicute eubacterial spores derived from healthy donors' fecal matter. It has breakthrough therapy designation from FDA.
In January, Seres granted the Nestlé Health Science subsidiary of Nestlé S.A. (SIX:NESN) exclusive rights to four gastrointestinal products, including SER-109, outside the U.S. and Canada (see BioCentury Extra, Jan. 11).
At the end of 1Q16, Seres had more than $300 million in cash. The company raised $153.8 million in a June 2015 IPO. Co-founding investor Flagship Ventures held 37% of Seres' shares as of February 2016, according to a regulatory filing.
In a new restructuring plan unveiled Friday, Takeda Pharmaceutical Co. Ltd. (Tokyo:4502) said it plans to "reduce and concentrate" its R&D in Japan and the U.S.
In a presentation, CMO and CSO Andrew Plump said Takeda's R&D organization will now be a "dual-centered" structure in Japan and Boston, with "lean regional centers" to help manage local studies and regional issues with global studies. He acknowledged a headcount reduction, but declined to say how many jobs would be affected.
Over the past few years, Takeda has winnowed down its disease focus to CNS, cancer and gastrointestinal disease, plus vaccines. The pharma has discontinued R&D in diabetes, sold its respiratory business and pipeline, and spun out or returned other assets (see BioCentury, May 30).
On Friday, Takeda said it will redouble its emphasis on operational efficiency, including restructuring R&D and optimizing relationships among its R&D, business and corporate functions.
Its R&D site in Shonan, Japan, will focus on CNS and regenerative medicines. Plump said that over time, Takeda plans to convert the site into a research park that houses scientists from other companies and institutions. He said the pharma also plans to create JVs and form spin-offs to address specific disease areas.
At its Boston site, Takeda will conduct R&D on oncology and GI disease, as well as immunomodulation as it relates to its core therapeutic areas. The site will be Takeda's development center and the primary home of its translational research and early clinical group. Plump said a "smaller biotech-like site" in San Diego will develop specialized technologies in the GI and CNS areas.
Takeda proposed closing its R&D site in Cambridge, U.K., but Plump said the company intends to spin off some of the site's discovery programs into a biotech start-up that will create jobs for its staff.
Takeda intends to move staff from its pharmaceutical sciences organization to the Shonan, Boston and San Diego R&D sites, Plump said. The pharmaceutical sciences organization, which bridges R&D and commercial manufacturing, is now spread across nine sites.
Plump also said Takeda is in "advanced discussions with a strategic development partner," and hopes to have a deal in place within the next couple of months. The deal would see Takeda "providing capabilities to the potential partner that allow for real end-to-end trial management," he added.
Takeda expects to record a one-time implementation cost of Y75 billion ($705 million) for the restructuring. As a result of the changes, the pharma expects to save Y18 billion ($169.2 million) annually, which it said it plans to re-invest into its pipeline.
AbbVie Inc. (NYSE:ABBV) reported 2Q16 financial results that beat estimates and raised full-year 2016 guidance. Continued strength in sales of autoimmune drug Humira adalimumab allayed some concerns about AbbVie's shrinking market share for its HCV drugs, while the company reiterated that it expects to defend Humira's IP against looming biosimilar competition.
Sales of Humira were $4.1 billion in 2Q16, up from $3.5 billion in 2Q15. The drug accounted for 65% of AbbVie's total 2Q16 sales of $6.45 billion, which rose from $5.5 billion in 2Q15 and beat the $6.2 billion consensus estimate.
AbbVie reported a non-GAAP EPS of $1.26, up from $1.08 in 2Q15 and topping the $1.20 consensus. It raised 2016 EPS guidance to $4.73-$4.83 from $4.62 to $4.82.
On a conference call Friday, Chairman and CEO Richard Gonzalez said the company's market share among HCV drugs had dropped from about 40% to "the single-digit range" due to competition from new entries and the company's decision not to match lower prices from competing products, particularly in public channels including the U.S. Department of Veterans Affairs. Sales of Viekira Pak ombitasvir/paritaprevir/ritonavir plus dasabuvir were $419 million during the quarter, up from $385 million in 2Q15. The company did not report sales of Technivie ombitasvir/paritaprevir/ritonavir.
In March, the VA added lower priced HCV drug Zepatier grazoprevir/elbasvir (MK-5172/MK-8752) from Merck & Co. Inc. (NYSE:MRK) to its national formulary, which also includes Viekira and Technivie. HCV drugs Daklinza daclatasvir from Bristol-Myers Squibb Co. (NYSE:BMY) and Harvoni ledipasvir/sofosbuvir and Sovaldi sofosbuvir from Gilead Sciences Inc. (NASDAQ:GILD) are also on the formulary (see BioCentury Extra, March 9).
Gonzalez also reiterated previous comments expressing confidence in Humira's ongoing patent protection. A biosimilar of the drug, ABP 501 from Amgen Inc. (NASDAQ:AMGN), is under FDA review, with an action date of Sept. 25. Amgen has said it could launch the biosimilar as early as 2017, while AbbVie argues that its patent protection is valid through 2022 (see BioCentury Extra, July 8).
Sales of blood cancer drug Imbruvica ibrutinib were $439 million in 2Q16, up from $107 million in 2Q16. In March, FDA expanded Imbruvica's label to include first-line treatment in chronic lymphocytic leukemia (CLL). It was already approved as a second-line therapy.
In a study published Thursday in Cell Reports, researchers at the Genentech Inc. unit of Roche (SIX:ROG; OTCQX:RHHBY) and AC Immune S.A. (Lausanne, Switzerland) developed a strategy that could make therapeutic antibodies safer for treating Alzheimer's disease and other neuroinflammatory conditions.
Gai Ayalon, a scientist in Genentech's neuroscience department, told BioCentury the study was prompted by the all-too-common occurrence of vasogenic edema in clinical trials of anti-beta amyloid antibodies to treat Alzheimer's disease. He said the field has long suspected those incidences were "microglial-driven events occurring because of the presence of the antibody." Microglia are phagocytic immune cells in the brain.
Ayalon said a CNS-targeted antibody works by binding to a target and then recruiting microglial cells to degrade it. But in neuroinflammatory conditions where the cell type is already chronically activated, further stimulation could exacerbate the pathology.
"What makes immunotherapy attractive is the degree of selectivity antibodies offer for the target," said Ayalon. "Antibodies are by definition immunoreactive molecules. And while the inflammatory response is a natural process that can be used to clear a target, when it becomes chronic it can be deleterious."
In the study, the collaborators engineered two point mutations into the Fc region of an anti-tau mAb to render it incapable of binding Fc gamma receptors (FCGRs) on microglial cells, and compared it to the same antibody without the mutations.
In cultures of microglia, the control antibody bound to immune cells, triggering the release of inflammatory cytokines. The mutant antibody neither bound microglia nor triggered cytokine release. In co-cultures of neurons and microglia, only the mutant antibody was able to decrease tau-related neurotoxicity. The mutant antibody also decreased tau pathology and disease progression in a mouse model of AD (see BioCentury Innovations, July 28).
Ayalon said the strategy of preventing microglial activation by antibodies should be applicable to "multiple CNS targets and indications."
He would not say whether the control antibody in the study is the same anti-tau mAb that the partners are studying in a Phase I trial for AD, nor would he discuss development plans for the new mAb.
Pfizer Inc. (NYSE:PFE) said Xeljanz tofacitinib met the primary endpoint in the Phase III OCTAVE Sustain trial evaluating the therapy as a maintenance treatment in adults with moderately to severely active ulcerative colitis (UC). A significantly greater proportion of patients receiving Xeljanz compared to placebo were in remission at week 52, the study's primary endpoint.
OCTAVE Sustain enrolled patients who completed and achieved a clinical response in two other Phase III studies, OCTAVE Induction 1 and 2. Last September, Pfizer said Xeljanz met those studies' primary endpoints (see BioCentury Extra, Sept. 21, 2015).
Pfizer also expects data this year from the long-term extension OCTAVE Open trial. It has said it expects to use data from all four OCTAVE studies to support regulatory submissions in UC. Spokesperson Steven Danehy declined to discuss Pfizer's regulatory plans.
The oral pan-Janus kinase (JAK) inhibitor is approved in more than 45 countries, including the U.S., to treat moderate to severe rheumatoid arthritis.
The U.K.'s Cancer Drugs Fund (CDF) was relaunched Friday, and is now accepting new drugs for inclusion.
In order to better control costs, NHS England and NICE revamped the CDF earlier this year, making it a "managed access" fund that pays for drugs NICE recommends conditionally as part of its appraisal process. Its budget is L340 million ($446.2 million).
Under the new scheme, the CDF can provide interim funding to make cancer drugs available after NICE has issued a positive draft recommendation, but before it issues final guidance. NICE is to issue final guidance within 90 days of an MAA's approval.
The new CDF is already covering four drug regimens that were recently recommended by NICE in draft guidance: lung cancer drug Zykadia ceritinib from Novartis AG (NYSE:NVS; SIX:NOVN); Opdivo nivolumab in combination with Yervoy ipilimumab from Bristol-Myers Squibb Co. (NYSE:BMY) for melanoma; Novartis' Mekinist trametinib plus Tafinlar dabrafenib for melanoma; and colorectal cancer drug Lonsurf trifluridine/tipiracil from Servier (Neuilly-sur-Seine, France).
The revamped CDF is also funding two drugs on an interim basis after NICE recommended them in draft guidance upon reappraisal. The old CDF had covered both. They are leukemia drug Bosulif bosutinib from Pfizer Inc. (NYSE:PFE) and Alimta pemetrexed from Eli Lilly and Co. (NYSE:LLY) as maintenance treatment for lung cancer.
In a statement, the Association of the British Pharmaceutical Industry said that companies and patients "should eventually both benefit from a more simplified process." The group said cancer drugs, particularly those for rarer cancers, are still at risk of being "routinely turned down for use unless there is greater flexibility in NICE's core appraisal process."
Under the revamped CDF, a NICE appraisal would raise issues to be addressed through the collection of real-world data and additional data from ongoing studies. Sponsors of drugs entering the fund have two years to collect additional data demonstrating the drugs' cost-effectiveness before NICE re-appraises the drug and either recommends it for routine use on the NHS or delists it (see BioCentury, March 14).
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