Mon, Nov. 2, 9:39 AM
- The FDA designates Merck's (MRK +0.3%) KEYTRUDA (pembrolizumab) a Breakthrough Therapy for the treatment of microsatellite instability high (MSI-H) metastatic colorectal cancer (CRC), the third such designation for the PD-1 inhibitor [advanced melanoma and advanced non-small cell lung cancer (NSCLC)].
- Tumors with microsatellite instability have defective DNA mismatch repair (MMR) systems, a process whereby cells recognize and repair genetic mismatches generated during DNA replication. A defective DNA MMR system allows the mismatched mutations to persist. The average tumor has dozens of mutations, but those with DNA MMR deficiency may have thousands, in particular in regions of repetitive DNA called microsatellites, which is a condition called microsatellite instability. Tumors with microsatellite instability are considered DNA MMR-deficient or MSI high. About 20% of Stage 2 CRC cases, 10% of Stage III and 5% of Stage IV are MSI high. MMR-deficiency is present in up to 20% of non-hereditary CRCs and most hereditary CRCs associated with Lynch Syndrome.
- A ongoing Phase 2 study, KEYNOTE-164, is assessing KEYTRUDA in previously treated MSI high CRC patients. A Phase 3, KEYNOTE-177, is planned for the treatment-naive population.
- KEYTRUDA is currently cleared for the treatment of melanoma and PD-L1-expressing NSCLC.
Tue, Oct. 27, 8:27 AM
- Merck (NYSE:MRK) Q3 results ($M): Total Revenues: 10,073 (-4.6%); Pharmaceutical: 8,925 (-2.3%); Animal Health: 825 (-6.8%).
- Net Income: 1,826 (+116.9%); EPS: 0.64 (+106.5%).
- Key Product Sales: Januvia: 1,014 (+8.7%); Zetia: 633 (-4.1%); Gardisil: 625 (+5.9%); Janumet: 562 (+11.3%); Remicade: 442 (-26.8%); Keytruda: 352 (+999%); Cubicin: 325 (+999%).
- 2015 Guidance: Total Revenues: $39.2B - 39.8B from $38.3B - 39.8B; EPS: $1.64 - 1.74 from $1.52 - 1.71; Non-GAAP EPS: $3.55 - 3.60 from $3.45 - 3.55.
Tue, Oct. 27, 6:54 AM
Mon, Oct. 26, 5:30 PM
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Mon, Oct. 26, 4:49 PM
Mon, Oct. 26, 10:27 AM
- Top-line results from a randomized, open-label Phase 2/3 clinical trial, KEYNOTE-010, demonstrated that Merck's (MRK -0.5%) KEYTRUDA (pembrolizumab) had a positive effect on delaying the progression of advanced non-small-cell lung cancer (NSCLC) compared to the commonly used chemotherapeutic docetaxel.
- The ~900-subject study assessed two doses of KEYTRUDA, the FDA-approved 2 mg/kg and the investigational 10 mg/kg, every three weeks versus docetaxel. Participants had failed prior systemic therapy for NSCLC and had PD-L1 tumor proportion scores (TPS) of at least 1%. Outcomes were assessed in all PD-L1-positive patients and those who were strongly PD-L1-positive (TPS of at least 50%).
- The top-line analysis showed that treatment with KEYTRUDA was associated with longer overall survival (OS) for both doses and both groups of PD-L1-positive patients, although it is unclear whether the effect was statistically significant. Treatment with both doses of KEYTRUDA showed superior progression-free survival (PFS) compared to docetaxel in patients with TPS of at least 50%. PFS in the KEYTRUDA cohort was numerically better but not statistically superior to docetaxel in the overall PD-L1-positive group (TPS at least 1%). The safety profile was consistent with previously reported studies in advanced NSCLC.
- The FDA cleared KEYTRUDA for the second-line treatment PD-L1-positive advanced NSCLC earlier this month. It was cleared for the treatment melanoma in September 2014.
- Previously: FDA clears Merck's Keytruda for second-line treatment of lung cancer (Oct. 2)
Fri, Oct. 23, 11:38 AM
- Results from a three-part Phase 2a proof-of-concept study assessing Bristol-Myers Squibb's (BMY +1.8%) second-generation HIV maturation inhibitor, BMS-955176, demonstrated encouraging antiviral activity and a favorable safety profile. The data were presented at the 15th European AIDS Conference in Barcelona.
- BMS-955176 is designed to inhibit one of the last steps of the HIV-1 viral life cycle when the virus breaks connections between structural proteins, which then undergo changes that produce fully mature infectious virus particles. This late-state disruption, which results in the release of immature HIV-1 particles that are unable to complete their life cycle, is a unique mechanism of action.
- The study results demonstrated BMS-955176's antiviral activity against HIV-1 both as monotherapy and in combination with other antiretrovirals and across patient subtypes (B,C), including those infected with the HIV-1 virus with changes to a key protein (Gag polymorphisms) that enabled it to fend off the effects of a first-generation maturation inhibitor.
- Part A of the randomized trial assessed one of four once-daily doses (5, 10,20, 40 mg) of BMS-955176 as monotherapy or placebo in 40 HIV-1 subtype B patients. 20 additional patients were later randomized to receive 80 mg and 120 mg once daily. All doses showed greater antiviral activity on day 11 than placebo with the 80 and 120 mg doses showing the highest mean knockdown of HIV-1 RNA (~96%).
- Part B assessed BMS-955176 administered with atazanavir (ATV) with or without ritonavir compared to a standard-of-care regimen of atazanavir and ritonavir plus tenofovir disoproxil fumarate/emtricitabine after 28 days of therapy. The median knockdown of HIV-1 RNA of <99% was similar between the 80 mg dose + ATV and the standard-of-care regimen.
- Part C assessed BMS-955176 (40 mg and 120 mg) as monotherapy vs. placebo for 10 days in 19 patients infected with HIV-1 subtype C. On day 11, the median HIV-1 RNA knockdown was highest in the 40 mg arm (~94%).
- The company intends to advance BMS-955176 to Phase 3 development.
- Related tickers: (GILD -1.3%)(MRK +1.3%)(ABBV +4.2%)
Tue, Oct. 20, 7:29 AM
- Oncolytics Biotech (NASDAQ:ONCY) is set to submit its IND to the FDA for clearance to begin a Phase 1b study of Merck's (NYSE:MRK) Keytruda (pembrolizumab) in combination with REOLYSIN (pelareorep) and chemotherapy in patients with advanced pancreatic adenocarcinoma.
- The open-label study will enroll adult patients with confirmed advanced or metastatic pancreatic adenocarcinoma who failed or did not tolerate first-line treatment. The primary endpoint is the safety and dose-limiting toxicities of REOLYSIN and chemo (gemcitabine or irinotecan or fluorouracil) in combination with Keytruda. Secondary endpoints include overall response rate, overall survival and progression-free survival. There will be an initial six to nine patient safety run-in followed by the enrollment of up to 15 additional participants.
- CEO Dr. Brad Thompson says, "This is the first study examining the effects of REOLYSIN in combination with a checkpoint inhibitor in human patients. It builds on our previous clinical work in pancreatic cancer as well as findings from multiple clinical and preclinical studies indicating the REOLYSIN can upregulate PD-1 and PD-L1.
- REOLYSIN has been designated an Orphan Drug for the treatment of pancreatic cancer by both the FDA and EMA.
Fri, Oct. 16, 7:55 AM
- Alios BioPharma, a unit of Janssen Pharmaceutical (NYSE:JNJ), initiates a Phase 2a clinical trial assessing the combination of AL-335, odalasvir (ACH-3102) and simeprevir (OLYSIO) in treatment-naive HCV-1 patients. Approximately 60 participants in the randomized, open-label, three-arm study will receive once-daily treatment for four, six or eight weeks. The primary endpoint is safety. Secondary endpoints include pharmacokinetics, the proportion of patients achieving sustained viral response (SVR) at four weeks, six weeks and eight weeks and the effect on the viral resistance profile after treatment. According to clinicaltrials.gov, the estimated final data collection date for the primary endpoint is February 2016. The estimated study completion date is August 2016.
- AL-335 is a nucleotide-based NS5B polymerase inhibitor. Odalasvir is an NS5A inhibitor and simeprevir is an NS3/4A inhibitor.
- In May Achillion Pharmaceuticals (NASDAQ:ACHN) granted Janssen an exclusive worldwide license to develop and commercialize HCV products and regimens containing one or more of Achillion's HCV assets, including odalasvir (ACH-3102), ACH-3422 and sovaprevir.
- Johnson & Johnson (JNJ) acquired Alios BioPharma in September 2014.
- Related tickers: (NASDAQ:GILD) (NYSE:MRK) (NYSE:ABBV) (NYSE:BMY)
Tue, Oct. 13, 9:38 AM
- Incyte (NASDAQ:INCY) and Merck (NYSE:MRK) expand their ongoing clinical collaboration with a new Phase 3 trial assessing Incyte's selective IDO1 inhibitor, epacadostat, in combination with anti-PD-1 Keytruda (pembrolizumab), for the first-line treatment of advanced/metastatic melanoma. The co-funded trial should commence in H1 2016.
- Under the terms of their partnership, the companies have agreed not to initiate new pivotal studies of an IDO1 inhibitor in combination with a PD-1/PD-L1 antagonist in advanced/metastatic melanoma with a third party for two years. During the period, each company will offer the other the opportunity to collaborate on any new pivotal study involving the two product classes for types of melanoma as well as lines of therapy outside of their current collaboration agreement.
Mon, Oct. 12, 8:00 AM
- Results from a randomized, double-blind, double-dummy Phase 4 study showed Amgen's (NASDAQ:AMGN) Prolia (denosumab) achieved greater gains in bone mineral density (BMD) than the intravenous biphosphonate zoledronic acid [Novartis' (NYSE:NVS) Zometa] in postmenopausal women with osteoporosis following treatment with oral biphosphonates. The data were presented at the American Society for Bone and Mineral Research Annual Meeting in Seattle.
- Biphosphonates [e.g. Merck's (NYSE:MRK) Fosamax (alendronate sodium)] are commonly used as first-line treatment for osteoporosis.
- The 12-month study enrolled 643 postmenopausal women with osteoporosis who had been taking oral biphosphonates for at least two years. They were randomized 1:1 to receive either subcutaneous denosumab 60 mg every six months plus intravenous placebo once yearly (n=321) or intravenous zoledronic acid 5 mg once yearly plus subcutaneous placebo every six moths (n=322).
- The primary endpoint was the change from baseline in lumbar spine BMD at month 12. The change in the denosumab arm was greater (+3.2%) than the zoledronic acid arm (+1.1%). The results were highly statistically significant (p<0.0001). The denosumab cohort also beat the zoledronic acid group in changes in BMD in the total hip, femoral neck and 1/3 radius.
- No new safety issues were identified. Both arms showed similar incidences of adverse events.
- Prolia, cleared by the FDA in June 2010, is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture, for the treatment of men with osteoporosis at high risk of fracture and men/women who are at high risk of fracture receiving certain therapies.
- Prolia generated almost $1.2B in sales over the past four quarters.
Fri, Oct. 9, 8:29 AM
- The UK's National Institute for Health and Care Excellence (NICE) issues a draft recommendation, called a Final Appraisal Determination or FAD, recommending Merck's (NYSE:MRK) KEYTRUDA (pembrolizumab) for the first-line treatment of adult patients with advanced melanoma.
- Several days ago, NICE issued final guidance recommending KEYTRUDA for the treatment of advanced melanoma after disease progression with ipilimumab [Bristol-Myers Squibb's (NYSE:BMY) Yervoy].
- KEYTRUDA, currently cleared in 39 countries, was the first medicine available through the UK Early Access to Medicines Scheme (EAMS), introduced in 2014, to help patients with life-threatening or debilitating diseases gain access to promising treatments before regulatory clearance is granted.
- NICE advises the National Health Service on costs, procedures and technologies with the aim of better managing the cost/benefit of services.
Thu, Oct. 8, 7:37 AM
- Australian biotech Bionomics Limited (OTCQX:BNOEF) extends its strategic collaboration, originally inked in July 2013, with Merck (NYSE:MRK) for the discovery and development of drugs for the treatment of chronic and neuropathic pain based on Bionomics' ionX and MultiCore drug discovery platforms.
- Specific financial aspects of the partnership are not disclosed, but Merck has agreed to purchase 21,659,230 ordinary shares of Bionomics at A$0.5938 which is a 29% premium to yesterday's closing price.
Fri, Oct. 2, 3:44 PM
- The FDA approves Merck's (MRK +1.1%) Keytruda (pembrolizumab) for the treatment of patients with advanced/metastatic non-small cell lung cancer (NSCLC) whose disease has progressed after other treatments and that express a protein called PD-L1 [such as Bristol-Myers Squibb's (BMY +3.2%) Opdivo (nivolumab)].
- The data supporting the sBLA was generated from a subgroup of 61 NSCLC patients within a larger study who progressed following platinum-based chemo and targeted therapies for EGFR/ALK mutations, if present. The subgroup's tumors all expressed PD-L1 as determined by the 22C3 pharmDx companion diagnostic test. Participants received 10 mg/kg of Keytruda every two to three weeks. The results showed that treatment with Keytruda shrank tumors in 41% of patients with the effect lasting as long as 9.1 months.
- The FDA designated Keytruda a Breakthrough Therapy for this indication.
- Reference labs Quest Diagnostics (DGX +2%) and LabCorp (LH +1.9%) will offer the 22C3 pharmDx test as a service. The kit was developed by Agilent's (A +2.7%) Dako unit.
Fri, Oct. 2, 10:46 AM
- Today is the FDA's PDUFA date under its Accelerated Review program for Merck's (MRK +0.3%) supplemental Biologics License Application (sBLA) seeking clearance of Keytruda (pembrolizumab) for the treatment patients with advanced non-small cell lung cancer whose disease has progressed on or after platinum-based chemo and an FDA-approved therapy for EGFR or ALK mutations, if present.
- Keytruda is currently cleared for the second-line treatment of melanoma.
Mon, Sep. 28, 1:56 PM
- The Japanese Ministry of Health, Labour and Welfare approves Merck's (MRK -2.7%) MARIZEV (omarigliptin) for the treatment of adults with type 2 diabetes. Japan is the first country to approve the medication.
- MARIZEV is a once-weekly DPP-4 inhibitor. The marketing application was supported by Phase 3 data that showed comparable efficacy and tolerability compared to once-daily DPP-4 inhibitor JANUVIA (sitagliptin).
- DPP-4 (dipeptidyl peptidase 4) inhibitors reduce glucagon and blood glucose levels by increasing incretin levels. Lowering glucagon increases insulin secretion.
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