Humira: Will AbbVie's Patents Keep Out Biosimilars For Its TNF-Blocker Blockbuster?
Markman Advisors • 21 Comments
Markman Advisors • 21 Comments
Thu, Oct. 20, 4:51 PM
- Results from a Phase 3 clinical trial assessing Amgen's (NASDAQ:AMGN) XGEVA (denosumab) compared to zoledronic acid (ZA) for the prevention of bone complications in newly diagnosed multiple myeloma (MM) patients achieved its primary endpoint. Full results will be submitted for presentation at a future medical conference and for publication. The data will also be submitted to regulatory authorities.
- The primary endpoint was a non-inferiority test defined by the time to the first skeletal-related event (SRE).
- The secondary endpoints were not met. They were measures of superiority as defined by the time to the first-and-subsequent SRE and time to the first on-study SRE.
- Bone lesions frequently occur in MM patients which increase the risk of bone complications. Denosumab targets a particular ligand pathway called RANK to prevent the formation, function and survival of osteoclasts, a type of bone cell that absorbs bone tissue.
- XGEVA is approved in the U.S. to prevent serious bone problems in patients with bone metastases from solid tumors but is not approved to prevent bone problems in MM patients.
Fri, Oct. 14, 4:13 PM
Fri, Oct. 14, 10:23 AM
- Bristol-Myers Squibb (BMY +0.3%) appears to have some work to do in order for cancer med Opdivo (nivolumab) to be routinely available through the UK's National Health Service (NHS) for lung cancer patients. Its advisory committee on costs and services, the National Institute for Health and Care Excellence (NICE) says the company needs to make a case to include Opdivo in its Cancer Drugs Fund (CDF), a government set-aside to pay for cancer medicines that have not been approved by NICE and, therefore, are not available within the NHS in England (Scotland, Wales and Northern Ireland do not have a similar program in place).
- NICE's appraisal committee concluded that nivolumab was not cost-effective for all patients with squamous and non-squamous advanced non-small cell lung cancer (NSCLC), but did appear to benefit some patients more than others. NICE's Carole Longson says, "Nivolumab appears to be more effective in certain lung cancer patients. However, we do not have the full picture yet and we need more evidence to find out the extent of this benefit. If the company puts forward a CDF proposal, nivolumab could be made available to some patients with lung cancer whilst more evidence is gathered on its value." The committee has asked the company to show Opdivo's cost-effectiveness in NSCLC patients with PD-L1 levels of 10% or more.
- Nivolumab is licensed in the UK for the treatment of advanced NSCLS patients who have been previously treated with chemotherapy, in addition to indications in melanoma and kidney cancer.
- Bristol-Myers is not alone it dealing with price hawk NICE. Alexion Pharmaceuticals (ALXN +1.1%) has had to run the gauntlet with Strensig (asfotase alfa), Amgen (AMGN +0.5%) with Repatha (evolocumab) and Roche (OTCQX:RHHBY +0.3%) with Gazyvaro (obinutuzumab) and Kadcyla (ado-trastuzumab emtansine).
Thu, Oct. 6, 3:32 PM
- Biotech investors are sitting on the sell button today. The iShares Nasdaq Biotechnology ETF (IBB -2.4%) is down on increased volume. Shares have retraced over 5% since the recent close of 300 on September 22.
- Alnylam (ALNY -48%) is leading the rout after it announced that it was dropping development of RNAi candidate revusiran.
- Representative tickers: (AMGN -0.3%)(BIIB -1.3%)(GILD -1.9%)(CELG -1.4%)(BMY)(MRK -0.7%)(PFE -1.2%)(VRTX -3%)(ALXN -2.2%)
Thu, Sep. 29, 8:11 AM
- Arrowhead Pharmaceuticals (NASDAQ:ARWR) is ahead 21% premarket on average volume in response to is announcement of two collaboration deals with Amgen (NASDAQ:AMGN) for RNA interference (RNAi) therapies for cardiovascular disease (CVD) based on its proprietary subcutaneous RNAi delivery platform.
- Under the first agreement, Amgen receives a global exclusive license to Arrowhead's RNAi ARC-LPA program, designed to reduce elevated lipoprotein(a), a risk factor for atherosclerotic CVD. The second agreement provides Amgen an option to a global exclusive license for an RNAi therapy for an undisclosed CVD target. Amgen is responsible for clinical development and commercialization under both contracts. Financial terms are not disclosed. The ARC-LPA transaction should close in Q4.
- Arrowhead will host a conference call this morning at 9:00 am ET to discuss the collaborations.
Wed, Sep. 28, 6:56 PM
- A Phase 3 clinical trial, ARISE, assessing Amgen's (NASDAQ:AMGN) erenumab (formerly AMG 334) for the prevention of migraine met its primary endpoint of a statistically valid reduction from baseline in monthly migraine days in patients with episodic migraine compared to placebo. Specifically, patients receiving erenumab experienced an average 2.9-day reduction from baseline in monthly migraine days versus an average 1.8-day reduction for placebo.
- The results will be submitted for presentation at a future medical conference and for publication.
- Results from a second Phase 3, STRIVE, are expected later this year.
- Erenumab, a fully human monoclonal antibody, inhibits the calcitonin gene-related peptide (CGRP) receptor, which is believed to transmit signals that cause incapacitating pain. It is being co-developed with Novartis (NYSE:NVS). Amgen retains commercial rights in the U.S., Canada and Japan and Novartis has commercial rights elsewhere.
Tue, Sep. 27, 11:32 AM
- Ligand Pharmaceuticals (LGND -9.3%) gets some rude treatment by the market in early trading. Shares are down on more than double normal volume in apparent response to the failure of Amgen's (AMGN -1.1%) Phase 3 study of a combination regimen including KYPROLIS (carfilzomib) for the treatment of certain multiple myeloma patients.
- Investors may be a bit premature on their perception that sales of KYPROLIS will be hampered by the negative results considering the company's statement that the standard-of-care for newly diagnosed multiple myeloma has moved away from the chemo agent melphalan, which was a component of the combo regimens investigated in the study. The long-term trial commenced in March 2013.
- Ligand receives sales-based royalties from 1.5 - 3.0% from KYPROLIS. In the most recent four quarters, Amgen booked $611M in sales for the drug which translated to a 2.5% royalty for Ligand or ~$15.3M, almost 21% of the company's revenues over the same time frame.
Tue, Sep. 27, 9:17 AM
- Shire plc (NASDAQ:SHPG) terminates its collaboration agreement with Momenta Pharmaceuticals (NASDAQ:MNTA) to develop and commercialize M923, a biosimilar to AbbVie's (NYSE:ABBV) HUMIRA (adalimumab). It made the decision after an assessment of its product portfolio following the Baxalta acquisition.
- Under the terms of the 2011 collaboration agreement between Baxalta and Momenta, the deal will terminate 12 months following the formal notice. Shire will continue to fund the M923 program until then, although preparations to transfer all clinical, regulatory and commercialization activities to Momenta will begin immediately.
- Momenta better get busy. The FDA just approved Amgen's (NASDAQ:AMGN) version and Samsung Bioepis' version, to be marketed by Biogen (NASDAQ:BIIB), is under regulatory review in Europe. Germany's Merck KGaA (OTCPK:MKGAF)(OTCPK:MKGAY) is also in the mix. Indian outfit Cadila Healthcare launched its HUMIRA biosimilar in India in September 2014.
Tue, Sep. 27, 7:46 AM
- A Phase 3 study, CLARION, assessing the combination of Amgen's (NASDAQ:AMGN) KYPROLIS (carfilzomib), melphalan and prednisone (KMP) compared to Takeda's (OTCPK:TKPHF)(OTCPK:TKPYY) VELCADE (bortezomib), melphalan and prednisone (VMP) over 54 weeks in patients with newly diagnosed multiple myeloma who were ineligible for hematopoietic stem cell transplant failed to achieve its primary endpoint of a statistically valid increase in progression-free survival (PFS).
- Subjects receiving KMP experienced median PFS of 22.3 months versus 22.1 months for VMP. The data for overall survival is not yet mature but the hazard ratio was 1.21 (there was a 21% higher risk of death or disease progression with KMP).
- The incidence of Grade 3 or higher adverse events were similar between the groups, 74.7% for KMP and 76.2% for VMP. The incidence of treatment-related deaths were 6.5% for KMP and 4.3% for VMP. The incidence of Grade 2 or higher peripheral neuropathy (peripheral nerve damage) was 2.5% for KMP and 35.1% for VMP.
- EVP of R&D Sean Harper, M.D., says, "The CLARION results, generated in the context of a melphalan-containing regimen, are disappointing, especially given the robust data we've seen in the second-line setting. However, the myeloma landscape has changed dramatically since the design of the CLARION study (started in March 2013) with very few newly diagnosed patients treated with melphalan-based regimens, particularly in the U.S. We remain committed to exploring KYPROLIS in combination with other agents to advance the treatment of multiple myeloma."
- The data will be submitted for presentation at a future medical conference and for publication.
- Share are down 1% premarket on light volume.
Mon, Sep. 26, 4:43 PM
- The FDA accepts for review Amgen's (NASDAQ:AMGN) Biologics License Application (BLA) seeking approval of romosozumab for the treatment of osteoporosis in postmenopausal women at increased risk of fracture.
- The FDA's action date (PDUFA) is July 19, 2017.
- Romosozumab is a monoclonal antibody that inhibits sclerostin, a protein that has anti-anabolic effects on bone formation. It has a dual effect of increasing bone formation and decreasing bone breakdown. It is being co-developed by Amgen and UCB. Amgen filed the BLA in July.
- Previously: Amgen and UCB's romosozumab reduced fractures in late-stage study in postmenopausal women with osteoporosis (Sept. 19)
Mon, Sep. 26, 1:10 PM
- The first patient has been enrolled in recent IPO Gemphire Therapeutics' (GEMP -0.4%) Phase 2b clinical trial, COBALT-1, assessing sole product candidate gemcabene for the treatment of patients with homozygous familial hypercholesterolemia (HoFH).
- The trial is assessing three doses (300 mg, 600 mg, 900 mg) of gemcabene in subjects on stable lipid-lowering therapy, including statins, ezetimibe [Merck's (NYSE:MRK) ZETIA] and Amgen's (AMGN -0.9%) Repatha (evolocumab). The primary efficacy endpoint is the change in LDL-C from baseline at 28, 56 and 84 days. According to ClinicalTrials.gov, the estimated study completion date is February 2017.
- Gemcabene is a once-daily orally available medication for patients unable to achieve normal levels of LDL-C or triglycerides with currently available therapies. It has a dual mechanism of action that blocks the production of hepatic triglyceride and cholesterol synthesis and enhances the clearance of VLDL (very low density lipoprotein). Specifically, it inhibits a liver protein called apolipoprotein C-III and may inhibit a liver enzyme called acetyl-CoA carboxylase. Gemphire licensed it from Pfizer in April 2011.
Fri, Sep. 23, 4:21 PM
Fri, Sep. 23, 9:34 AM
- The FDA's decision on Amgen's (AMGN +0.1%) Biologics License Application (BLA) seeking approval of ABP 501, a biosimilar to AbbVie's (ABBV) Humira (adalimumab), should happen today since the PDUFA date is Sunday, September 25.
- In July, the Advisory Committee voted 26 - 0 backing approval.
- Read now Amgen's Biosimilar Approval And Astra's Anti-PD-L1 Data
Tue, Sep. 20, 9:51 AM
- A Phase 3 clinical trial, GLAGOV, assessing the ability of Amgen's (AMGN +0.9%) anti-cholesterol med Repatha (evolocumab) to modify the buildup of artery plaque met its primary and secondary endpoints. Detailed results will be presented on Tuesday, November 15 at the American Heart Association Scientific Sessions in New Orleans, LA.
- GLAGOV randomized 968 subjects to receive monthly injections of Repatha 420 mg or placebo. Participants had confirmed coronary artery disease and were receiving optimized statin therapy. All were undergoing coronary catheterization.
- The primary endpoint was the nominal change from baseline in percent atheroma (plaque) volume (PAV) at Week 78 as determined by intravascular ultrasound. Secondary endpoints were regression from baseline in PAV at Week 78, nominal change in total atheroma volume (TAV) from baseline to Week 78 and regression in TAV from baseline at Week 78.
- Evolocumab is a monoclonal antibody that inhibits convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces the liver's ability to remove low-density lipoprotein cholesterol (LDL-C) from the blood.
Mon, Sep. 19, 7:16 AM
- A Phase 3 clinical trial, FRAME, assessing Amgen (NASDAQ:AMGN) and UCB's romosozumab (AMG 785) in reducing the incidence of new vertebral fractures in postmenopausal women with osteoporosis met its co-primary endpoints. The results were published in the New England Journal of Medicine and presented yesterday at the Annual Meeting of the American Society for Bone Mineral Research in Atlanta, GA.
- FRAME randomized 7,180 women to receive either monthly 210 mg subcutaneous injections of romosozumab or placebo for 12 months. The romosozumab group showed a statistically significant 73% reduction in the relative risk of a new vertebral fracture through Month 12 compared to placebo (0.5% versus 1.8%; p<0.001), the first co-primary endpoint.
- The difference in fracture risk reduction persisted through Month 24 after both groups were transitioned to denosumab (Prolia) in the second year of the study, with the romosozumab cohort showing a 75% reduction in the relative risk of vertebral fracture (0.6% versus 2.5%; p<0.001), the second co-primary endpoint.
- Romosozumab was also superior to placebo in reducing all symptomatic fractures with a 36% reduction in the relative risk of clinical fracture through Month 12 and a 33% lower risk through Month 24.
- In a sub-study of 126 patients, treatment with romosozumab increased bone mineral density in the lumbar spine and total hip by 9.7% and 4.7%, respectively, at Month 6 and 13.3% and 6.8%, respectively, at Month 12, compared to placebo (p<0.001). Bone mineral density continued to increase in the romosozumab group after transitioning to denosumab with increases of 17.6% and 8.8%, respectively, at Month 24 versus placebo (p<0.001).
- The incidence of adverse events and serious adverse events were balanced between the treatment groups. Injection site reactions occurred in 5.2% of the romosozumab cohort compared to 2.9% for placebo.
- Romosozumab is a monoclonal antibody that inhibits sclerostin, a protein that has anti-anabolic effects on bone formation. It has a dual effect of increasing bone formation and decreasing bone breakdown. It is being co-developed by Amgen and UCB. Amgen filed a Biologics License Application (BLA) with the FDA in July.
- Previously: Amgen submits BLA in U.S. for osteoporosis candidate romosozumab (July 22)
Fri, Sep. 16, 8:07 AM
- The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) adopts a positive opinion recommending approval of Amgen's (NASDAQ:AMGN) Parsabiv (etelcalcetide) for the treatment of secondary hyperthyroidism in adult patients with chronic kidney disease on hemodialysis.
- Etelcalcetide is a novel calcimimetic that suppresses the secretion of parathyroid hormone. It acts by binding to and activating the calcium-sensing receptor on the parathyroid gland, which causes a decrease in the hormone. If approved, it will be the first calcimimetic agent that can be administered intravenously three times a week at the end of a dialysis session.
- Last month, Amgen received a Complete Response Letter (CRL) from the FDA regarding its marketing application in the U.S.
- Read now Parsabiv NDA Fails; Implications For Amgen