Author: Jean-Claude Muller, 穆卓Executive Editor at BtoBioInnovation, jcm@btobioinnovation.com

Acquisitions /mergers/joint-ventures

Medivation is reportedly responding to interest from several firms including Pfizer and Amgen but turned down Sanofi’s original offer of $52.50 per share. The share has been trading as high as $63 in recent days. In the meantime Sanofi is preparing to become hostile and plans to nominate eight people to replace current Medivation directors as early as next week according to CNBC.

Quintiles (Research Triangle, NC, USA) and IMS Health (Danbury, CT, USA) have announced plans to merge in an all-stock deal worth nearly $9 billion and aim to create a company called Quintiles IMS with annual revenues of more than $7 billion. The new company will offer a distinctive global real-world evidence solutions platform underpinned by “a leading portfolio” of anonymous patient records, technology-enabled data collection and observational research experts, to help address critical healthcare issues of cost, value and patient outcomes. Under the terms of the deal IMS Health shareholders will own approximate 51.4 percent of the combined company with Quintiles shareholders owning the remaining 48.6 percent.

Neovacs (Paris, France) forms a joint venture, with Stellar Biotechnologies (Port Hueneme, CA, USA) named Neostell, to be established in Paris (France). Stellar Biotechnologies makes a protein for immunotherapy treatments using a unique sea snail only found off the coastal shores of a small part of California. Under the terms of the deal Neovacs will own 70% of the new company whereas Stellar Biotechnologies will own 30%

Jazz Pharmaceuticals (Dublin, Ireland) acquires Alizé Pharma II (Lyon, France), a company specializing in the development of treatments for cancer and metabolic diseases, for $20.3 million.

Business

Chiesi Farmaceutici (Parma, Italy) acquires three cardiovascular drugs from The Medicines Company’s (Parsippany, NJ, USA) for up to $972 million. The acquired drugs are Cleviprex, Kengreal and Argatroban, which are used to treat high blood pressure or prevent blood clots. In December, The Medicines Company sold its hemostasis treatments to Mallinckrodt for $410 million to finance the development of its promising pipeline of drugs, including two heart disease treatments.

Pfizer enters a strategic partnership with Wave Life Sciences (Cambridge, MA, USA) to develop nucleic acid treatments for the treatment of genetically defined targets of metabolic disorders in a deal worth up to $900 million. Under the terms of the agreement Pfizer will us its hepatic targeting technology for enhanced delivery to the liver and Wave will bring its proprietary stereopure drug-development platform. Wave will advance up to five programs from discovery through to the selection of clinical candidates, at which point Pfizer may elect to exclusively license the programs. Two targets have already been declared and include Wave’s Apolipoprotein C-III program. Pfizer will make an upfront payment of $40 million and payment of up to $871 million.

Takeda Pharmaceutical partners with Prosetta Biosciences (San Francisco, CA, USA) to explore novel treatments for central nervous system disorders using Prosetta’s novel small-molecule antiviral drug discovery platform based on its cell-free protein synthesizing systems. Financial terms were not disclosed but the deal comes a few months after Takeda joined with other investors to raise $31 million in financing for Prosetta through a private placement.

….and receives a $38 million grant from the Bill & Melinda Gates Foundation to develop, license and supply at least 50 million doses per year of Sabin-strain inactivated poliovirus vaccine to more than 70 developing countries. As part of a global plan to eradicate the last cases of polio countries one will need to switch from using oral polio vaccine to the inactivated polio vaccine to make sure the disease does not reappear. The vaccine will be manufactured at Takeda’s facility in Hikari (Japan)

AbbVie extends its cystic fibrosis (CF) partnership with Galapagos (Mechelem, Belgium) by raising the milestone payments from $350 million to $600 million under the expanded collaboration. AbbVie and Galapagos are working to develop a triple CF transmembrane conductance regulator combination therapy intended to address 90% of patients with CF. Both companies said plan to identify and develop multiple candidates and backups for each component of the combination—three Galapagos compounds consisting of two corrector molecules and a potentiator.

Daiichi Sankyo acquires the rights to develop Cell Therapy’s (Cardiff, UK) Heartcel product for the Japanese market for an upfront payment of $18.1 million. The Heartcel product is designed to reduce scarring of the muscle caused by a heart attack or heart failure and was granted a fast-track filing status in Europe last October.

Approval of drugs and vaccines

US FDA approves

Acadia Pharmaceutical’s (San Diego, CA, USA) Nuplazid or pimavanserin, as a treatment for Parkinson’s disease-associated psychosis. Pimavanserin is the first selective serotonin inverse agonist which target the serotonin 5-HT_2A receptor with 40-fold selectivity for this site over the 5-HT_2C receptor and no significant affinity or activity at the 5-HT_2B receptor or dopamine receptors.

…and Flamel Technologies’ (Lyon, France) Akovaz or ephedrine sulfate, for the treatment of hypotension in the event of a crisis during a surgical procedure.

The European Commission approves:

Bristol-Myers Squibb and AbbVie’s immunotherapy Empliciti, for the treatment of multiple myeloma in combination with Celgene’s Revlimid or lenalidomide and dexamethasone.

….and a fifth indication for Bristol-Meyers Squibb’s Opdivo, or nivolumab in combination with Yervoy, or ipilimumab as a treatment for advanced melanoma regardless of their BRAF mutation. Recent late stage clinical results showed that the combination was more effective than Yervoy alone.

Drugs at clinical stage

US FDA grants fast track to Therabron Therapeutic’s (Rockville; MD, USA) CG100, a compound based on the CG100 component of the recombinant human Club Cell 10 kDa protein rhCC10, as a preventive therapy against chronic lung disease related to premature birth.

US FDA grants orphan status to AstraZeneca’s selumetinib, a MEK inhibitor, for adjuvant treatment of patients with stage III or IV differentiated thyroid cancer. Radioactive iodine is recommended for these patients, however, a small proportion do not benefit from treatment because they don’t express sufficient sodium/iodine symporter which is key for iodine uptake into cells. 

Pfizer will test a combination of three immunotherapies for the treatment of solid cancers. The reported cocktail includes the checkpoint inhibitor avelumab (a fully human anti-PD-L1 IgG1 monoclonal antibody being developed with Merck), utomilumab and another experimental therapy referred to as OX40. The study aims at determining how much manipulation of the immune system the body can handle.

…and reports showed strong activity with its meningitis vaccine TRUMENBA in two large-scale Phase 3 trials against invasive meningococcal B strains. TRUMENBA was approved by the US FDA in October 2014 to prevent invasive disease caused by Neisseria meningitidis serogroup B in people 10-25 years old.

Oxford Biomedica (Oxford, UK) reports data from two clinical studies indicating “ground breaking” long-term sustained and dose dependent gene expression with its LentiVector gene therapy therapy OXB-101 or Prosavin for the treatment of Parkinson’s disease as well as with RetinoStat for the treatment of wet-age related macular degeneration.

Innovative Cellular Therapeutics (Shanghai, China) in collaboration with First Affiliated Hospital of Zehjiang University report complete remission in 9 out of 10 patients with relapsed/refractory B lymphoblastic leukemia who were treated with CAR (chimeric antigen receptor)-T cell therapy.  Novartis, Juno Therapeutics and Kite Pharma were, up to now, the only companies able to demonstrate this level of success with CAR-T therapies.

Bayer terminates a clinical trial assessing riociguat, a stimulator of soluble guanylate cyclase, in pulmonary hypertension associated with idiopathic interstitial pneumonia on the bases of serious safety concerns. The drug is currently the only treatment approved in the US for use in two types of pulmonary hypertension (WHO Groups 1 and 4), where it is sold under the brand name Adempas.

Medical Devices and Diagnosis News

Scientists from the University of California Davis Medical Center Glaucoma Service in San Francisco have developed a small and thin silicon ring that can be placed on the surface of the eye, like a contact lens, which delivers bimatoprost, a prostaglandin analog, over a course of six months.

Science and Technology

Previous studies had identified the biological players in loss of appetite: one was an immune molecule called interleukin 18 (IL-18), another was a brain structure called the Bed Nucleus of the Stria Terminalis (BST), which has neurons that project to the Lateral Hypothalamus (LH), a brain region that controls appetite. New research has now linked the two elements together. It started with the discovery of the expression of IL-18 receptors in neurons of the anterior BST. In mouse BST brain slices not exposed to IL-18, glutamate, an excitatory neurotransmitter, strongly activates a subset of BST neurons projecting to the LH. The activation of these BST-LH neurons leads to the release of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, on target neurons. The GABA release inhibits neuronal activity in the LH. Normal amounts of GABA released into LH leads to a normal appetite. When IL-18 binds to its receptors it reduces glutamate release, leading to less activation of specific neurons, reduced GABA signaling and a loss of appetite. Mice with IL-18 injected directly into the anterior BST ate significantly less than mice that received a control substance.

Johns Hopkins researcher create an accurate 3D-virtual heart to predict patients at arrhythmia risk. "Our virtual heart test significantly outperformed several existing clinical metrics in predicting future arrhythmic events," said Natalia Trayanova, Johns Hopkins professor of biomedical engineering and lead author on the study, in a statement. "This non-invasive and personalized virtual heart-risk assessment could help prevent sudden cardiac deaths and allow patients who are not at risk to avoid unnecessary defibrillator implantations." The research team formed predictions based on the MRI records of 41 patients who had survived a heart attack, but were left with damaged cardiac tissue that can lead to arrhythmias

Cost, Pricing and Market Access

Health insurer Cigna signs a value-based agreement with Sanofi/Regeneron Pharmaceuticals and Amgen covering the payment of Praluent, or alirocumab, and Repatha, or evolocumab, the two new PCSK9 inhibitors for the treatment of hypercholesterolemia. The contracts established the cost of the drugs on how well patients respond to the treatment. Praluent lists for $14,600 while Repatha lists for $14,000 per year. Cigna will get bigger discounts if the drugs don’t deliver the expected results for patients. Cigna will also determine whether there are cardiovascular improvements related to treatment. Cigna has value-based contracts in place covering drugs for heart failure, diabetes, multiple sclerosis and hepatitis C and was one of the first insurers to sign on to Novartis’ pay-for-performance plans for its heart failure drug Entresto.

An active week within UK National Institute for Health and Care Excellence with:

The recommendation of Sanofi/Regeneron Pharmaceutical’s Praluent and Amgen’s Repatha. “The committee concluded that both drugs are effective in reducing levels of ‘bad cholesterol’ when compared with placebo, ezetimibe or statins in people with hypercholesterolaemia or mixed dyslipidaemia,” noted Professor Carole Longson MBE, Director of the NICE Centre for Health Technology Evaluation. However, she stressed that both drugs are relatively expensive, costing more than £4,000 per patient per year compared with about £350 for ezetemibe. “Therefore the draft guidance recommends alirocumab and evolocumab as a cost effective use of NHS resources only with the discounts agreed with the companies and only for people with hypercholesterolaemia or mixed dyslipidaemia whose cholesterol is still not under control despite making changes to their lifestyle and taking other cholesterol-lowering drugs.” 

The recommendation of GlaxoSmithKline of Benlysta, or belimumab, for the treatment of lupus, nearly five years after the drug first won European approval and after several rejections on the ground that its value didn’t justify its price. NICE latest draft guidelines now say treatment with Benlysta can be funded by the health service, but only under a managed access agreement agreed between GSK and NHS England, which will provide the drug at a discounted price, and on the condition that data is collected to help address remaining questions over its efficacy.

The rejection of Bristol-Myers Squibb’s Opdivo or nivolumab, as an immunotherapy for the treatment of adults with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose disease has progressed after prior chemotherapy. 

BMS says the rejection comes despite the offer of several schemes to make Opdivo more cost effective in the lung cancer setting, including funding treatment after the first year.

Miscellaneous

US FDA is warning about potentially fatal skin reactions tied to Eli Lilly’s antipsychotic Zyprexa (olanzapine) products.

Pfizer, follows more than 20 US and European drug companies, in imposing strict control on the distribution of its products to ensure that none are used in lethal injections.

According to a recent report from the Tufts Center for the Study of Drug Development only 12% of drugs that enter human clinical testing gain regulatory approval. This figure almost did not change over the last 15 years.

JHL Biotech (Wuhan, China) opens the first-of-its-kind and largest monoclonal antibody manufacturing facility in China, constructed by GE Healthcare Life Science, around a single-use bioreactor technology which is compliant with international regulatory requirements.

Johnson & Johnson is facing a federal probe over its relationships with pharmacy benefit managers. The demand for documents is the latest Department of Justice move to investigate a drugmaker under the False Claims Act. The U.S. Attorney’s office sent J&J’s Janssen Pharmaceuticals unit a civil investigative demand for information about its contractual relationships with PBMs. The demand covers Jan. 1, 2006 to the present and "certain pharma products." It was issued in connection with an investigation under the False Claims Act, the company disclosed in its quarterly filing with the Securities and Exchange Commission.

Bioevents

Strategic Alliance Management Congress on May 16-18 in Philadelphia (USA)

China BIO Partnering Forum on May 18-19 in Suzhou (China)

4^th Annual IBA World Life Sciences Conference on June 3-4 in San Francisco (USA)

BIO International Convention on June 6-9 in San Francisco (USA)

BIO Pharm America on September 13-15 in Boston (USA)

7^th Innovation Days on October 3-4 in Paris (France)

BIO Europe on November 7-9 in Cologne (Germany)

BIO Latam on November 29-30 in San Juan (Puerto Rico)

Biofit 2016 on November 30-December 1 in Lille (France)

IMPORTANT NOTICE

This document has been prepared by btobioinnovation and is provided to you for information purposes only.  The information contained in this document has been obtained from sources that btobioinnovation believes are reliable but btobioinnovation does not warrant that it is accurate or complete. The views presented in this document are those of btobioinnovation’s editor at the time of writing and are subject to change.  btobioinnovation has no obligation to update its opinions or the information in this document.