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BioCentury Extra
As published Friday, May 29, 2015 5:56 PM PST


  • Opdivo NSCLC, HCC data showcased at ASCO

    Bristol-Myers Squibb Co. (NYSE:BMY) shed $4.55 to $64.60 after data presented at the American Society of Clinical Oncology (ASCO) meeting detailed the survival benefit from Opdivo nivolumab from Bristol-Myers Squibb Co. (NYSE:BMY) in patients with non-squamous non-small cell lung cancer (NSCLC). The first Opdivo data to treat hepatocellular carcinoma (HCC) were also presented at the meeting.

    Data from the Phase III CheckMate -057 study showed that treatment with Opdivo led to median overall survival (OS) of 12.2 months vs. 9.4 months in previously-treated non-squamous NSCLC patients receiving docetaxel (HR=0.73; 96% CI: 0.59, 0.89; p=0.00155). In a subgroup of patients with PD-L1 expression in >1% of their tumor cells, the median OS in the Opdivo arm exceeded 17 months vs. 9 months for docetaxel (HR=0.59; 95% CI: 0.43, 0.81). In April, BMS had said it stopped CheckMate -057 early after reviewers concluded Opdivo met the primary endpoint of superiority to docetaxel in improving OS in previously-treated non-squamous NSCLC patients.

    Opdivo led to an improved overall response rate of 19.2% vs. 12.4% in the docetaxel arm (p=0.0235), but missed the secondary endpoint of improving median progression-free survival (PFS) (2.3 vs. 4.2 months; HR=0.92; 95% CI: 0.77-1.11; p=0.393). Spokesperson Priyanka Shah declined to discuss BMS's plans to seek a label extension for Opdivo to treat non-squamous NSCLC.

    In previously disclosed data from the CheckMate -017 study to treat squamous cell NSCLC, Opdivo had led to a median OS of 9.2 months vs. 6 months for docetaxel; data from the study showed tumor PD-L1 status did not predict OS outcomes (see BioCentury Extra, May 13).

    In a separate Phase I/II trial of Opdivo to treat hepatocellular carcinoma (HCC), patients who progressed on or were intolerant of treatment with Nexavar sorafenib from Bayer AG (Xetra:BAYN) received 0.1-10 mg/kg of Opdivo for up to two years. Interim data from 42 evaluable patients showed Opdivo led to a 19% response rate, including two complete responses and six partial responses, and a 12-month OS rate of 62%.

    Prior studies have shown an ORR ranging from 2-7% in Nexavar-treated patients with advanced liver cancer. Nexavar, an inhibitor of CRAF (RAF1) and multiple receptor tyrosine kinases, is marketed to treat several cancers including HCC.

    Opdivo, a human IgG4 mAb against PD-1, has Fast Track designation in the U.S. to treat NSCLC, renal cell carcinoma (RCC) and melanoma. FDA first approved the drug in December 2014 to treat unresectable or metastatic melanoma in patients previously treated with the company's Yervoy ipilimumab, including BRAF V600 mutation-positive patients treated with Yervoy plus a BRAF inhibitor.

    In an interview with BioCentury TV in April, Gideon Blumenthal, team leader of thoracic oncology at FDA's Center for Drug Evaluation and Research (CDER), cautioned against emphasizing median survival data for Opdivo and other immunotherapies. "When we're looking at these immunotherapy agents, the median is not the message" because it obscures a small subset of patients who derive great benefit, he said (see BioCentury TV, April 22).

  • FDA approves Rapamune for rare lung disease

    FDA approved Rapamune sirolimus from Pfizer Inc. (NYSE:PFE) to treat lymphangioleiomyomatosis (LAM), a rare, progressive, cystic lung disease in women. Rapamune is the first approved drug in the indication; it has Orphan Drug and breakthrough therapy status and received Priority Review.

    The agency based its approval on the 89-patient Phase III MILES trial, in which patients receiving Rapamune had significantly slower decreases in forced expiratory volume at one second (FEV1) vs. placebo over a 12-month period.

    The rapamycin non-calcineurin antagonist immune suppressant, which targets the FK506 abinding protein (macrophilin-12), is marketed to help prevent organ rejection in patients receiving kidney transplants.

  • Management tracks

    Neurology play Cerecor Inc. (Baltimore, Md.) named Ronald Marcus CMO and head of regulatory affairs. Marcus was CMO at Spinifex Pharmaceuticals Pty. Ltd. (Preston, Australia).

  • Keytruda data show correlation with MMR biomarker

    Merck and Co. Inc. (NYSE:MRK) announced the first clinical results showing a correlation of benefit from treatment with PD-1 inhibitor Keytruda pembrolizumab in patients with DNA mismatch repair (MMR) deficiency. In a Phase II trial, colorectal cancer (CRC) patients with MMR-deficient tumors had an objective response rate (ORR) of 62% vs. no responses among MMR-proficient patients.

    Merck intends to begin a new registrational Phase II study, KEYNOTE-164, in mid-2015 to study Keytruda in CRC patients based on MMR status.

    The completed study assessed two co-primary endpoints in 48 patients with previously treated metastatic cancers: ORR and progression-free survival (PFS) at 20 weeks. Patients had either MMR-deficient or MMR-proficient CRC, or other repair-deficient cancers. The study met the ORR primary endpoint in the repair-deficient cohorts; ORR was also 60% in repair-deficient cancers other than CRC.

    Median PFS and overall survival were not reached in repair-deficient CRC, while PFS was 2.3 months and OS was 7.6 months in repair-proficient CRC. Disease control rates were 92% and 70% in repair-deficient CRC and other cancers, respectively, vs. 16% in repair-proficient CRC.

    Results from the study, led by researchers at the Sidney Kimmel Comprehensive Cancer Center at The Johns Hopkins University, will be presented on Saturday at the American Society for Clinical Oncology (ASCO) meeting.

    Studies will also be presented at ASCO investigating Keytruda in non-small cell lung cancer (NSCLC), advanced melanoma, renal cell carcinoma (RCC), esophageal cancer, ovarian cancer, small cell lung cancer (SCLC), and urothelial cancer (see BioCentury Extra, May 14).

    Keytruda, a humanized IgG4 mAb against PD-1, was approved in September to treat advanced melanoma.

  • Farydak/Kyprolis ORR tops Velcade combo in MM

    Data due to be presented Tuesday at the American Society of Clinical Oncology meeting in Chicago showed a combination of Farydak panobinostat from Novartis AG (NYSE:NVS; SIX:NOVN) and Kyprolis carfilzomib from Amgen Inc. (NASDAQ:AMGN) led to an 82% objective response rate (ORR) in a Phase I/II trial to treat relapsed or refractory multiple myeloma.

    Walter Capone, president and CEO of the Multiple Myeloma Research Foundation, told BioCentury last year that the combo could serve as a potential replacement for Farydak plus Velcade bortezomib as a "more appropriate and more beneficial" regimen for MM. The Phase III PANORAMA-1 trial of Farydak plus Velcade and dexamethasone had led to an ORR of 61% in relapsed or refractory MM patients (see BioCentury, Nov. 17, 2014).

    The Farydak/Kyprolis trial included 26 evaluable patients. Severe thrombocytopenia occured in 31% of patients.

    In PANORAMA-1, patients receiving the Farydak combo had twice as many on-study deaths and almost 50% more non-fatal serious adverse events than those receiving only Velcade and dexamethasone, leading FDA's Oncologic Drugs Advisory Committee (ODAC) to vote 5-2 in November that Farydak's progression-free survival (PFS) benefit did not outweigh the safety risks of treating MM patients who have received at least one prior therapy.

    In February, FDA granted accelerated approval to Farydak in combination with Velcade and dexamethasone. The drug's label includes a boxed warning describing risks of severe diarrhea, severe and fatal cardiac events, arrhythmias and electrocardiogram changes. Farydak is approved with a Risk Evaluation and Mitigation Strategy (REMS). Johnson & Johnson (NYSE:JNJ) and the Millennium Pharmaceuticals Inc. unit of Takeda Pharmaceutical Co. Ltd. (Tokyo:4502) market Velcade, a proteasome inhibitor (see BioCentury Extra, Feb. 23).

  • SV Life Sciences seeking $400M for sixth fund

    SV Life Sciences has set a goal of $400 million for SV Life Sciences Fund VI, according to an SEC filing. The firm, which did not respond to inquiries, closed its $523 million Fund V in 2010 at $523 million. It invests in biotech and pharma, medical devices, healthcare services and healthcare information technology.

    The firm's investments include neuropathic pain company Convergence Pharmaceuticals Ltd., which Biogen Inc. (NASDAQ:BIIB) acquired; oncology company Bicycle Therapeutics Ltd. (Cambridge, U.K.); and ophthalmic play Ophthotech Corp. (NASDAQ:OPHT).

  • FDA issues draft guidance on reporting CMC changes

    FDA issued draft guidance advising pharmaceutical companies on which changes must be reported to FDA with respect to chemistry, manufacturing and controls information for approved drugs and biologics.

    Sponsors must notify FDA, through a supplement or inclusion in an annual report, of any changes to CMC information that meet the definition of an "established condition." These include descriptions of the product, manufacturing process, facilities and equipment, and "elements of the associated control strategy" that assure process performance and quality of an approved product.

    The draft, entitled "Established Conditions: Reportable CMC Changes for Approved Drug and Biologic Products," is open for comments until July 31.

  • China FDA increasing registration fees

    China Food and Drug Administration (CFDA) said it would increase registration fees for domestic drugs from RMB35,000 ($5,642) to RMB624,000 ($100,589).

    At the U.S.-China Joint Commission on Commerce and Trade (JCCT) held in Chicago in December, China said it would eliminate its drug application backlog within two to three years by adding regulatory personnel, increasing funding and streamling review.


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