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

 Editor’s Note

A terrorist attack occurred in the French coastal city of Nice killing at least 84 people and leaving several hundred others wounded, when a truck careened through crowds of people watching Bastille Day fireworks on the “Promenade des Anglais”. Victims include nationals from France, Armenia, Morocco, Switzerland, Russia and the US. This is the third major terrorist attack taking place in France over the last 18 months.  I have very special sympathy for the people of Nice, since I did spend most of my summer holidays in this city when I was a teenager

Zika virus

Almost 600 cases of Zika infection have been reported among pregnant women in the US with seven infants being born with microcephaly and the first Zika-related death reported earlier this week.  The victim is an elderly Salt-Lake City women who contracted the disease while traveling to a region with a Zika outbreak. Nevertheless US Congress has still not approved any money to support the 1.1 billion emergency funding to combat the disease presented by President Obama.

A few weeks after Sanofi, GlaxoSmithKline is now committing to enter the Zika R&D field through a project with the National Institutes of Health in the US in order to find and develop a new vaccine. Over the past few months, GSK has run feasibility studies and now says it’s ready to move forward with technology called self-amplifying mRNA.

Acquisitions /mergers/joint-ventures

According to the Sunday Times, AstraZeneca is considering an offer of $10 billion to acquire Medivation, which seems insufficient considering the recent rejected sweetened $11 billion offer from Sanofi made last week.

GE Healthcare (Chalfont St Gilles, UK) acquires BioSafe Group (Lake Geneva Region, Switzerland), a supplier of integrated cell bioprocessing system, in order to substantially increase its presence in the cell therapy business. John Flannery, president and CEO of GE Healthcare, said he believes cell therapy will be "transformative in health care" "We want to double down on life sciences, and especially so in the cell therapy business. This more than doubles our capability right now in cell therapy and we think we can easily have a $1 billion-plus business in cell therapy in the next 10 years" he said. GE estimates there are now 375 active T-cell therapy programs, and seven companies with a focus on CAR-T. Producing the therapies, however, is extremely complex, since it involves extracting cells from an individual, altering them to sharpen their ability to kill cancer cells and then infusing them back into a patient. This, effectively, makes the production process an integral part of the product, which is where GE comes in. While GE has no intention of ever marketing medicines, it plans to offer an "end-to-end" service to drug companies via a range of tools, from bioreactors for growing cells to software systems for treatment delivery. Financial terms of the deal were not disclosed

Nichi-Iko Pharmaceutical (Tokyo, Japan) acquires Sagent Pharmaceuticals (Schamburg, Ill, USA) for $736 million. The purchase comes less than a month after Sagent acquired five Abbreviated New Drug Applications (ANDAs) from Teva Pharmaceutical Industries for $40 million—products which had to be divested by Teva as a precondition to its $40.5 billion acquisition of Allergan’s generics business. The deal is expected to support Nichi-Iko’s biosimilar product pipeline and boost its US presence in injectable products and generic drugs.

Cell Medica (London, UK) acquires Delenex (Schlieren/Zurich, Switzerland) and gets access a single-chain variable fragment technology (scFv) to target the system of chimeric antigen receptor (CAR) therapies it is co-developing with Baylor College of Medicine (Houston, TX, USA). Financial terms were undisclosed.

Business

Bayer gains extended access to X-Chem (Waltham, MA, USA) based DNA-encoded libraries of small molecules with more than 120 billion molecules for small-molecule drug discovery in expanding its ongoing collaboration. The expanded partnership is focused on the discovery of novel lead structures for complex targets in areas of high unmet medical needs. Bayer could pay as much as $528 million under the multiyear agreement. Bayer is among several pharma companies that have inked collaborations with X-Chem; others include AstraZeneca, Pfizer, and Roche. “With multiple successes across our partnerships, the DEX™ platform has been broadly validated to deliver novel chemical entities against a wide array of targets, including difficult targets," added X-Chem CEO Rick Wagner.

Servier (Neuilly, France) enters a partnering deal with Sorrento Therapeutics (San Diego, CA, USA) to develop STI-A1110, a second wave PD-1 checkpoint inhibitor. “We have tested STI-A1110 in preclinical studies conducted at Servier and we believe that, used in combination with several products from our portfolio, it will lead to the development of new treatments for hematological as well as solid tumor cancers,” said Dr. Jean-Pierre Abastado, director of the Oncology Innovation Therapeutic Pole for Servier. Under the terms of the deal Servier will make a $27.5 million upfront payment and as a much as $780 million in various milestones.

Boehringer Ingelheim teams up with University of Dundee (Scotland, UK) to develop proteolysis-targeting chimeric molecules (PROTACs) a new class of drugs designed to degrade proteins and targeting immune-oncology and respiratory diseases. PROTACs are designed to remove disease-causing proteins by triggering their labeling as “expired,” resulting in their removal by the cell’s ubiquitin-proteasome system. PROTACs are made of a moiety that binds the target and a moiety that binds an ubiquitin ligase enzyme, and as a result they are likely to exceed the size of conventional oral drug molecules.

Approval of drugs and vaccines

US FDA approves:

Shire’s Xiidra or lifitegrast ophthalmic solution for use in treating signs and symptoms of dry eye disease.

an expanded use of Pfizer’ Prevnar, a pneumonia vaccine, in adult patients ages 18 to 49. The vaccine, which protects against diseases caused by 13 strains of Streptococcus pneumoniae, was previously approved for use in children 6 weeks to 17 years old and in adults at least 50 years old.

…and a one-per-month dosing of Amgen’s Repatha, or evolocumab, a PCSK9 inhibitor for the treatment of hypercholesterolemia. Patients can now self-administer a single subcutaneous dose of 420 mg of evolocumab using the hands-free Pushtronex device. The original dosing regimen, which remains in place, is 140 mg every two weeks. This new dosing gives Amgen a clear advantage over Sanofi/Regeneron’s Praluent, its only competitor with the same mechanism of action.

Drugs at clinical stage

US FDA grants breakthrough status to Loxo Oncology’s (Stamford, Conn, USA) LOXO-101, a selective oral tropomyosin receptor kinase inhibitor (TRK) -a member of the neurotrophin receptor family-, as a treatment for unresectable or metastatic solid tumors with NTRK-infusion proteins.

US FDA grants rare pediatric status to AbbVie’s ABT-414, an antibody drug conjugate, for the treatment of children with diffuse intrinsic pontine glioma, a pediatric brain tumor.

US FDA grants orphan status to:

NLS Pharma’s (Stans, Switzerland) mazindol, for the treatment of narcolepsy, a chronic, debilitating neurological disease commonly presenting with excessive daytime sleepiness, fragmented nighttime sleep, sleep paralysis and cataplexy.

And to iBio’s (New York City, NY, USA) iBio-CFB02, a biotherapeutic anti-fibrotic agent based on a plant-made protein, for the treatment of systemic sclerosis. Systemic sclerosis is a fibrotic disorder that impacts the connective tissue of the skin and internal organs, as well as the walls of blood vessels. No approved drug has proven effective to address the disease.

US FDA grants fast-track to Lundbeck’s (Valby, Denmark) and Otsuka’s (Tokyo, USA) idalopirdine, for the treatment of mild to moderate Alzheimer’s disease, as an adjunctive therapy to acetylcholinesterase inhibitors. Idalopirdine is a selective 5HT6 receptor antagonist believed to modulate the balance between the excitatory glutamatergic neurons and the inhibitory GABAergic interneurons. When used as an adjunct to donepezil, idalopirdine potentiates the effects of acetylcholine levels and on neuronal activity in the cortex and hippocampus.

A FDA panel voted unanimously in favor of an approval of Amgen’s ABP501, a biosimilar version of AbbVie’s Humira, for all indications now approved for Humira.

Less than a week after US FDA had put Juno’s CAR-T clinical trial on hold after three deaths had occurred, Juno reported that the agency has lifted the halt on its lead CAR-T program. Juno is citing the addition of the chemotherapy agent fludarabine to its preconditioning of patients as a likely culprit.

Medical Devices and Diagnosis News

US FDA approves Novocure’s (St Helier, Jersey, UK) for its second-generation Optune system for the treatment of glioblastoma. The device is a smaller, lighter follow-up to its Tumor Treating Fields delivery system, which will be more convenient for patients to use. The wearable device delivers noninvasive therapy via four adhesive patches to the region of the brain where the tumor is located.

In June, 2016 the European Council (EC) endorsed the agreement reached with the European Parliament in May to override the current directives that lead to a CE mark with new legislation that overhauls the rules covering everything from bandages to heart valves to MRI scanners, from simple pregnancy test kits to complex in vitro diagnostics (IVDs). The final results of the agreed upon legislation, one package for medical devices and a second for IVDs, is that absolutely every product with a CE mark will need to be recertified under the new regulations, which are stricter, and will require new levels of documentation, in many cases clinical evidence that has not previously been required.

Cost, Pricing and Market Access

Sepsis is as serious as heart attack, according to NICE. The National Institute for Health and Care Excellence says all health professionals must consider the possibility of sepsis in all patients who may have an infection. Sepsis starts when the immune system overreacts to an infection and begins to damage the body itself, leading to organ failure and in some cases death. According to the UK Sepsis Trust, thousands of deaths could be avoided through faster recognition of the condition and treatment. The problem is that sepsis can be difficult to diagnose with certainty, as symptoms can vary between patients – some get high temperature, others a fast heart beats or chills, and so it is often mistaken for common infections such as flu. Quick identification and early treatment are key to avoid death from sepsis and improve chances of a full recover says NICE, noting that a recent report found that in 36 percent of cases there were delays in identifying the condition.

According to a Global Data report the diabetes market will account for almost $60 billion in 2025 because of a growing number of patients and a more aggressive treatment approach. That is almost the double of the $31.2 billion in brand and generic drugs recorded in 2015. The reports mentions GLP-1 drugs as the best poised to grow by 12.4% annually through the next decade.  The GLP-1s “in my opinion, should grow,” one European opinion leader told Global Data, “because basically, whenever they have been compared to insulin as an injectable treatment [for] type 2 diabetes, the results were at least as good, if not a little bit better.”

Miscellaneous

Ipsen (Boulogne-Billancourt, France) names David Meek as its new CEO. He was the former head of oncology at Baxalta prior to Shire’s closed the buyout of the Baxter spinoff. “His experience in the U.S., Europe, and international markets as well as his deep knowledge of oncology will be invaluable,” Marc de Garidel, the new non-executive chairman, said in an announcement about the change.

BREXIT. UK scientists fear of being dropped from future European projects funded by the EU. In a confidential survey of the UK’s Russell Group universities, The Guardian found cases of British academics being asked to leave EU-funded projects or to step down from leadership roles because they are considered a financial liability. In one case, an EU project officer recommended that a lead investigator drop all UK partners from a consortium because Britain’s share of funding could not be guaranteed. The note implied that if UK organisations remained on the project, which is due to start in January 2017, the contract signing would be delayed until Britain had agreed a fresh deal with Europe. British researchers receive about £1bn a year from EU funding programmes such as Horizon 2020, but access to the money must be completely renegotiated under Brexit.

AstraZeneca has filed a lawsuit to prevent the US Food and Drug Administration from approving the sale of generic versions of its cholesterol drug Crestor. Crestor's initial patent protection has come to an end but AstraZeneca recently bagged an extra seven years' exclusivity for a rare pediatric indication, and is now seeking to extend this for all uses of the drug. The firm has applied for a temporary court order to stop the FDA from allowing more Crestor generics to get approved until a final decision on this exclusivity is made. Senator Bernie Sanders and various US representatives have written to FDA Commissioner Robert Califf urging the regulator to approve the stream of applications to sell generic versions of AZ' drug, noting that this has the potential to "drastically reduce healthcare costs".

Bioevents

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.