Biopharmaceutical News Week # 16
Protein Sciences (Meriden, CT, USA) announces a collaboration with Sinergium Biotech and Mundo Sano both located in Argentina to advance the development of its Zika vaccine
According to the Sunday Times AstraZeneca has made a formal offer worth around £7 billion to acquire Medivation (South San Francisco, CA, USA) and has entered internal talks about the offer. Last week we had reported that Medivation had turned down an offer by Sanofi.
AbbVie enters two oncology collaborations:
One with argenx (Breda, The Netherlands and Ghent, Belgium) to develop and commercialise ARGX-115, a monoclonal antibody targeting GARP, a novel immune checkpoint, as a treatment of immuno-oncology diseases in a deal worth up to $685 million. Under the terms of the deal AbbVie will make an upfront of $40 million, a near term milestone of $20 million and additional contingent development, regulatory and commercial payments of up to $625 million. argenx will retain co-promotion rights in the European Union and in the Swiss Economic Area.
One with the University of Chicago (USA) to advance research focusing at various areas of oncology including lung, breast, prostate, colorectal and hematological cancers. Financial terms of the five-year collaboration were not disclosed.
Boehringer Ingelheim and Eli Lilly are partnering on two clinical trials to investigate the efficacy of Jardiance, or empaglliflozin, an inhibitor of the sodium glucose co-transporter-2 (SGLT-2), as a treatment of chronic heart failure. In the EMPA-REG OUTCOME trial, Jardiance was the first diabetes treatment ever to demonstrate a reduction in the risk of cardiovascular death in a dedicated cardiovascular outcomes trial. As well as cutting cardiovascular death by 38 percent this trial also showed that Jardiance reduced the risk of hospitalisation for heart failure. The new trials are planned to enroll people with chronic heart failure both with and without type 2 diabetes.
Heptares Therapeutics (London, UK) and Kymab Limited (Cambridge, UK) have entered a strategic collaboration to discover, develop and commercialise novel antibodies targeting G protein-coupled receptors (GCPR) with a main focus on immune-oncology. Under the terms of the agreement Heaptares will apply its StaRplatform to produce stable antigens and Kymab will use its human antibody technology to generate the appropriate antibodies. Financial terms were not disclosed.
GlaxoSmithKline enters into a collaboration with Sanford Burnham Prebys Medical Discovery Institute (La Jolla, CA, USA) to study brain function and seek out new therapeutic targets for neurological disorders. The SBP-GSK Center for Translational Neuroscience, will bring together experts from both parties to investigate factors influencing brain function and reverse or slow down neurodegeneration, with the aim of finding novel therapeutic targets. Financial terms of the three-year collaboration were not disclosed.
Approval of drugs and vaccines
To the best of your knowledge, no approval of a new drug or a new vaccine by the US FDA, the European Commission or the Japanese Ministry of Health, Labor and Welfare was announced this week.
Drugs at clinical stage
Novel immunotherapies acting as checkpoint inhibitors are showing impressive novel clinical benefits in several forms of cancer. Oncologists now consider that patients using checkpoint inhibitors, who survive a certain length of time (3 to 4 years) will probably not see their disease recur because their immune system appears to eradicate or control their tumors. The new findings also strongly support the use of appropriate combination therapies.
According to National Cancer Institute (NCI) data Bristol-Myers Squibb, Opdivo or nivolumab showed a 34% five-year survival rate for metastatic melanoma patients versus a 16.6% rate for patients taking other treatments. BMS also showed that Opdivo, in combination with Yervoy, displayed a two-year overall survival rate of 69%, compared to 53% for Yervoy alone, in patients with BRAF wild type associated melanoma, with 22% of patients with a complete response.
Bristol-Meyers Squibb reports that patients with metastatic squamous cell carcinoma of the head and neck treated with Opdivo compared to patients treated with methotrexate, docetaxel, or cetuximab, experienced a 30 % reduction in the risk of death, with a median overall survival of 7.5 months versus to 5.1 months.
US FDA grants breakthrough status to Merck’s Keytruda, a humanised monoclonal antibody that works as an immunotherapy by blocking the interaction between PD-1 and its ligands for the treatment of relapsed or refractory classical Hodgkin lymphoma. Keytruda is already approved in the US for unresectable or metastatic melanoma as well as for some patients with non-small cell lung cancer.
US FDA grants orphan status to:
Marinus Pharmaceuticals’ (Radnor, PA, USA) ganaxolone, a small molecule inhibitor of GABA, for the treatment of status epilepticus, an emergency situation form of epilepsy characterized by prolonged or repeated grand mal seizures.
…and to GW Pharmaceuticals’ (London, UK) Epidiolex or cannabidiol for the treatment of Tuberous Sclerosis Complex, a rare genetic disorder causing non-malignant tumors in several organs with the brain and skin being the most affected tissues. Last month the company had reported a positive primary endpoint in the treatment of Dravet syndrome, a rare form of child epilepsy.
Merck & Co’s Zepatier, a hepatitis C treatment, has induced cure as high as 96% in patient populations with HCV genotypes 1, 4 or 6 with inherited blood disorders, including haemophilia A/B, von Willebrand disease, beta thalassaemia and sickle cell anaemia. Zepatier, a fixed-dose combination of the NS5A inhibitor elbasvir and an NS3/4A protease inhibitor grazoprevir, was approved by the US FDA earlier this year for use, with or without ribavirin, to treat adult patients with chronic HCV-1 or HCV-4 infection with or without cirrhosis. The drug application is currently under review in Europe.
Novartis’ Afinitor, or everolimus, significantly reduced treatment-resistant seizures in patients with tuberous sclerosis complex (TSC), a rare genetic disorder, in a phase 3 trial. Everolimus is currently the only approved non-surgical option indicated for treating non-cancerous brain and kidney tumors in certain patients with the condition.
Mitsubishi Tanabe Pharma (Osaka, Japan) indicated that Radicut or edaravone also known as MCI-186, was efficacious in a phase 3 study of amyotrophic lateral sclerosis (ALS). The MCI-186-19 study met its primary endpoint of mean change in the ALS Functional Rating Scale-Revised at 24 weeks, with a frequency of adverse events similar to placebo. Radicut was approved in Japan for ALS in 2015 and holds orphan designation in Europe and in the US.
Merck & Co drops the development of omarigliptin, a once-weekly DPP-4 inhibitor for the treatment of diabetes, after it became clear that the investigational drug was not as safe as Januvia, including its cardiovascular and hepatobiliary profiles The decision comes with no surprise considering the beneficial cardiovascular effects of Boehringer Ingelheim and Eli Lilly’s Jardiance (see above) and Novo Nordisk’s Victoza, a GLP-1 drug. These new late stage clinical results may jeopardize the development and medical success of the entire DPP-4 class.
Medical Devices and Diagnosis News
Researchers from the Massachusetts Institute of Technology in Cambridge (USA), led by Dr. Laura Indolfi, have developed a small implantable device for delivering chemotherapy drugs directly to pancreatic tumors. The device is a thin, flexible film that can be loaded with drugs, rolled into a narrow tube and inserted into a catheter. Once it is implanted in the pancreas, the film unfolds and conforms to the shape of the tumor. The drugs embedded in the film are released over a predetermined period of time. The film is designed so the drugs only release from the side that is in contact with the tumor, minimizing side effects on nearby organs. Pancreatic cancer is the third leading cause of cancer deaths and has a very low survival rate because it is very difficult to get chemotherapy drugs into the pancreas, which is located deep inside the abdomen. Injections of chemotherapy also often fail because pancreatic tumors have few blood vessels through which the drugs can enter, and they often surround themselves with a thick, fibrous coating that keeps drugs out. Laura Indolfi also noted that the film acted as a physical barrier that reduced metastasis to nearby organs.
A team of scientists from Yale University School of Medicine in New Haven (USA) led by Gary Desir have found that renalase, a protein mainly produced by the kidney, which works as an enzyme to metabolize catecholamines, may be of importance for the growth of pancreatic cancers and could become a biomarker for the disease and a target for treatment. "We have discovered that pancreatic cancer cells misuse the renalase pathway to help them proliferate, and we have developed monoclonal antibodies of renalase that can kill pancreatic cancer cells and treat tumors in mice” said Desir.
Science and Technology
Scientists at the University of North Carolina (UNC) School of Medicine and Sanford Burnham Prebys Medical Discovery Institute (SBP) have identified the human host protein NLRX1 which is responsible in the weakening of our immune response to HIV and other viruses and which may explain why they are not cleared from our systems. The findings have important implications for discovering novel HIV antiviral therapies and creating effective viral vaccines. “Importantly, we were able to show that deficiencies in NLRX1 reduce HIV replication, suggesting that the development of small molecules to modulate the innate immune response may inhibit viral transmission and promote immunity to infection," said Sumit Chanda from SBP, co-senior author of the study. "Our discovery that NLRX1 reduces the immune response to HIV is similar to the discovery of host immune checkpoints, such as PD-L1 and CTLA-1, that control the immune response to cancer," said Jenny Ting (UNC) co-senior author of the study.
A team of scientists from the Nanyang Technological University (Singapore) have developed magnetic micro-sized bubbles coated with cancer drugs and iron oxide which can be guided to gather at a tumor site and then release the payload when ultrasound vibration is applied to the microbubbles.
Cost, Pricing and Market Access
The UK National Institute for Health and Care Excellence (NICE) has recommended:
PTC Therapeutic’s Translarna as a treatment for patients with Duchenne muscular dystrophy, but only in connection with a managed access agreement (MAA) being drawn up with National Health Services The drug is priced at £222,000 per year (before discount). Translarna got conditional approval from the European Commission in August 2014 and is currently available to patients in 23 countries. The conditional approval could nevertheless be turned down after the failure of a confirmatory Phase 3 trial. US FDA has refused to accept a marketing application for the drug, on grounds that it was “not sufficiently complete to permit a substantive review”.
And Sanofi’s Jevtana (cabazitaxel) in combination with prednisone or prednisolone to treat metastatic hormone relapsed prostate cancer in people whose disease has progressed during or after docetaxel chemotherapy. However, Jevtana should only be used if the person has an eastern cooperative oncology group (ECOG) performance of 0 or 1, and has had 225 mg/m2 or more of docetaxel. NICE had initially rejected Jevtana because of concerns about its cost-effectiveness compared with standard treatments such as abiraterone, enzalutamide or radium-223 dichloride. But Sanofi then increased the discount and confirmed that it can supply the drug in intravenous bags instead of vials, reducing waste and increasing its cost-effectiveness.
According to Bloomberg, Valeant CEO Michael Pearson spent 9 hours under questioning in advance of a public hearing before the Senate Special Committee on Aging scheduled on April 27. The US congressional pricing probes which extend beyond Valeant to other companies that have instituted large and sudden price hikes on their drugs, are only part of the trouble afflicting Valeant. The Canadian drugmaker also faces federal subpoenas relating not only to drug pricing but also to its relationship with specialty pharmacy Philidor Rx Services and its accounting for that relationship.
Major Investments are being made in European Manufacturing Plants:
Novo Nordisk has announced an €100 million expansion of its insulin production site in Chartres (France) and should add roughly 250 new jobs.
Sanofi has announced that it will invest about €300 million to expand its current rare disease drug production site in Geel (Belgium) to become a multi-product site including novel biologicals and expects to add roughly 100 new jobs.
Shire has announced an investment of $400 million into a new manufacturing facility at its current Piercetown (Ireland) site to manufacture a broad range of biologics products and expects to create around 400 new jobs.
Merck versus Merck. Germany based Merck KGaA and US-based Merck & Co are both claiming infringement allegations about the use of their Merck trademark. Merck & Co (USA) does business outside the US as Merck Sharp & Dohme (MSD). German Merck KGaA does business in the US as EMD Group. Coexistence agreements about these trademarks have been in existence since 1955 and 1970, but recent events mainly due to digitalized media and content of various websistes have complicated the matter. The recent new “rebranding” campaign by Merck KGaA, referring as the “Original” has added some fuel to the ongoing fire.
Three years after the bribery allegations which hit GlaxoSmithKline in China, the British pharma company is now undergoing an internal probe into allegations that its subsidiary in Yemen could have bribed government employees to influence purchasing decision and increase sales of its drugs. In addition GSK is under scrutiny that it had some of its own paid employees holding posts at the government health ministry.
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