A great deal of work will be required to pave the road for the use of real world evidence in regulatory decisions, wrote FDA Commissioner Robert Califf and 14 other FDA staff members in a commentary published Thursday in the New England Journal of Medicine. The article sets a tone of caution just as the 21st Century Cures Act and PDUFA reauthorization goals commit the agency to create a framework for the use of real-world evidence to make decisions about postapproval studies of drugs and their approval in supplementary indications (see BioCentury, Dec. 5).
The article describes the definition of real-world evidence as "elusive." The authors believe it refers to healthcare information "derived from multiple sources outside typical clinical research settings, including electronic health records (EHRs), claims and billing data, product and disease registries, and data gathered through personal devices and health applications."
It warns that the "allure of analyzing existing data may lead to flawed conclusions," and says this "concern is especially salient in light of the growing proliferation of precision molecular medicine and treatments for rare diseases, many of which are anticipated to undergo review in accelerated approval programs."
Real-world evidence could play an important role in reviewing such applications, the authors note, which adds to the urgency of developing rigorous methods for collecting and analyzing such information. The authors express optimism about "long-term prospects for the evolution of mature, robust methodologic approaches to the incorporation of real-world evidence into therapeutic development and evaluation," but emphasize that "caution is still needed, and expectations of 'quick wins' resulting from the use of such evidence should be tempered accordingly."
Horizon Pharma plc (NASDAQ:HZNP) dropped $4.36 (22%) to $15.03 on Thursday after it said Actimmune interferon (IFN) gamma-1b missed the primary endpoint in the Phase III STEADFAST trial to treat Friedreich's ataxia. The company said it will discontinue the candidate's development in the indication.
Compared to placebo, Actimmune failed to significantly improve change from baseline in the modified Friedreich's Ataxia Rating Scale (FARS-mNeuro) at 26 weeks. The candidate also failed to improve secondary endpoints, including activities of daily living (ADL), timed 25-foot-walk test (T25FW), Friedreich's Ataxia Rating Scale scores and other neurologic tests.
The trial enrolled 92 patients and was conducted by Horizon and the Friedrich's Ataxia Research Alliance.
Actimmune is approved in the U.S. to treat chronic granulomatous disease (CGD) and severe, malignant osteopetrosis.
Radius Health Inc. (NASDAQ:RDUS) lost $6.43 (12%) to $47.07 on Thursday after announcing early data from two Phase I trials of RAD1901 to treat estrogen receptor (ER)-positive breast cancer.
In a safety expansion cohort of a U.S. Phase Ib trial, RAD1901 led to confirmed partial responses (PRs) in two of 20 heavily pretreated ER-positive, HER2-negative advanced breast cancer patients.
The selective ER modulator also led to a PR in one of the first three patients enrolled in the high-dose cohort of a separate European Phase I trial, which is is enrolling postmenopausal ER-positive, HER2-negative breast cancer patients who received up to three prior lines of endocrine therapy in the metastatic setting.
Both studies are ongoing. The European study is to enroll five more patients at the high dose, and eight at a lower dose.
Radius spokesperson Lori Gorski said the company plans to meet with FDA to discuss next steps, including Phase II trials.
Radius presented the data at the San Antonio Breast Cancer Symposium (SABCS).
Immuno-oncology company Eutilex Co. Ltd. (Seoul, South Korea) raised W21 billion ($18.9 million) in a series A round from DS Asset Management, Kolon Investment, G.N. Tech Venture and SNU Bio Angel.
Eutilex said the money will support a Phase II study of lead candidate 4-1BB, an autologous T cell therapy targeting tumor necrosis factor (TNF) receptor superfamily member 9 (4-1BB; TNFRSF9; CD137). The company declined to disclose what indications will be evaluated in the trial.
Eutilex is also developing preclinical candidates EU-101, a human mAb targeting 4-1BB; and EU-102, a human mAb that converts regulatory T cells into effector T cells to permit tumor infiltration.
The funds also will support construction of a GMP manufacturing facility.
Blueprint Medicines Corp. (NASDAQ:BPMC) raised $125 million through the sale of 5 million shares at $25 in a follow-on led by Goldman Sachs, Morgan Stanley, Cowen, JMP Securities and Wedbush PacGrow. The price is a 12% discount to Blueprint's close of $28.43 on Tuesday, before the offering was announced after market.
The stock added $1.46 on Thursday to $27.66.
Last week, Blueprint said BLU-285 led to partial responses (PRs) in seven of 28 evaluable patients in a Phase I trial to treat gastrointestinal stromal tumors. The candidate is an inhibitor of stem cell factor (SCF) receptor tyrosine kinase (c-Kit; KIT; CD117) exon 17 mutations and platelet derived growth factor receptor A (PDGFRA; PDGFR2; CD140A) with the D842V amino acid substitution (see BioCentury Extra, Dec. 1).
In an amicus brief filed to the U.S. Supreme Court, acting U.S. Solicitor General Ian Gershengorn recommended that the court review a lower court's decision preventing the launch of a biosimilar until 180 days after FDA approval. The Solicitor general argued that the six-month delay was not intended by the U.S. Congress when it passed the Biologics Price Competition and Innovation Act (BPCIA).
The U.S. Court of Appeals for the Federal Circuit (CAFC) had considered the specific intent of language in the law requiring a biosimilar's sponsor to give the manufacturer of its reference product 180-day notice before marketing the biosimilar. In July 2015, CAFC ruled that the notice can be given only after FDA has approved the biosimilar's BLA. The ruling delayed the launch of Zarxio filgrastim-sndz from the Sandoz unit of Novartis AG (NYSE:NVS; SIX:NOVN). Zarxio is a biosimilar of Neupogen filgrastim from Amgen Inc. (NASDAQ:AMGN) (see BioCentury Extra, July 21, 2015).
The amicus brief argued that a biosimilar's sponsor may give such notice prior to the biosimilar's approval, and that the six-month delay enforced by CAFC undermines procedures laid out in BPCIA to encourage early litigation of patent claims.
In February, Sandoz petitioned the Supreme Court to review the CAFC decision. In June, the Supreme Court invited the solicitor general to file the brief (see BioCentury Extra, Feb. 17).
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