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

Editor’s Note

Paris, Berlin, Brussels, Nice and now London have recently been facing horrible terrorist attacks aimed at killing people and destroying our democracies. The incredible resilience of all the harmed or injured individuals, of their families and of many of the citizens of the targeted cities constitutes a formidable reply to all types of terrorism.

Breaking News

After meeting with US President Donald Trump, House Speaker Paul Ryan withdrew the bill to replace Affordable Care Act, or ObamaCare, after a growing number of defections from moderate and ultra-conservative Republicans occurred in the final hours before the vote on Friday. The decision came one day after President Trump delivered an ultimatum to House lawmakers warning that they must vote Friday to repeal the current law or concede that Obama’s major achievement would remain in place.

Mergers, Acquisitions and Joint Ventures

Sanofi is rumored to be in close negotiation to acquire Flexion (Burlington, MA, USA) and get access to Zilretta, or FX006, a pain drug for treating osteoarthritis, currently under review at the US FDA. Spokespersons at both companies did not comment, but people close to one of the company indicated that extensive due-diligence were ongoing.

Business

X-Chem Pharmaceuticals (Waltham, MA,USA) partners with Astellas Pharma (Tokyo, Japan) to discover novel lead compounds for complex drug targets of interest to Astellass using X-Chem collection of DNA-encoded DEX^TM libraries containing more than 120 billion compounds. DEX—short for DNA-Encoded X-Chem—is designed to discover novel lead compounds against a wide range of targets, based on proprietary innovations in library design, screening methodology, and bioinformatics. According to X-Chem, the library is screened as a mixture using affinity-based binding to a target of interest. Certain rare molecules in the library that bind to the target can be fished out, while the rest are washed away. DNA sequencing is then used to detect molecules that are enriched when bound to the target. X-Chem says its approach allows additional chemical reactions to be usable in DNA-encoded library synthesis. Astellas has the option to license identified lead compounds. Astellas will make a $16 million upfront, followed by research funding as well as license and option fees as the collaboration proceeds which could reach as much as $100 million per target.

…and with Ono Pharmaceuticals (Osaka, Japan) to discover “multiple promising high impact oncology targets” using X-Chem’s DEX^TM libraries. Ono will have the option to license identified lead compounds. Financial terms of the deal were not disclosed, but Ono will make an upfront payment as well as milestones payments.

Bristol-Myers Squibb extends its 2014 existing immune-oncology discovery collaboration with CytomX (South San Francisco, CA, USA) in adding up eight new projects: six in oncology and two outside of cancer. Under the terms of the deal, BMS will make a $200 million upfront and as much as $3.6 billion in milestones, as well as royalties on sales.

Arix Bisosciences (London, UK) enters a collaboration with the Lead Discovery Center GmbH (LDC, Dortmund, Germany), Max Planck Innovation GmbH (Munich, Germany) and the University of Leeds to develop new therapeutics for metabolic diseases based on the discoveries from these organisations. Under the terms of the deal, Arix will fund and manage experimental work building on discoveries from the faculty of cardiovascular medicine and diabetes at the University of Leeds and LDC, focusing on the development of antagonists of a novel target for a variety of metabolic indications.

GlaxoSmithKline and Regeneron will enter a new project with UK Biobank and get free access to patient samples in return for covering the costs of sequencing and after a period of exclusivity the data will be of use for wider use. The UK Biobank’s pool of data and samples is drawn from half a million anonymous patients and it will take three to five years to complete the entire sequencing. Sequencing will focus specifically on the 1% to 2% of the genome known as the exome, or the protein encoding regions of the genome, which is believed to have the most relevance for drug therapy. Although the costs of gene sequencing are falling, it remains expensive to conduct on a large scale – to sequence data from all 500,000 participants in the BioBank would require an investment of some $150 million. Consequently, the BioBank said the injection of funds from GSK and Regeneron was a tremendous boost

Approval of drugs and vaccines

The European Commission has approved Amgen’s Amgevita, marking the first European license for a biosimilar version of AbbVie’ Humira. Amgen indicated it had received marketing authorisation for “all available indications” for its biosimilar Humira, including moderate-to-severe rheumatoid arthritis, psoriatic arthritis and moderate-to-severe Crohn's disease. Humira was approved for the first time back in 2003.

The European Medicines Agency has given a positive guidance to Actinium Pharmaceuticals (New York City, NY, USA) regarding Iomab-B as a treatment for acute myeloid leukemia (AML). Iomab-B (BC8-I-131 construct), via the monoclonal antibody BC8, targets CD45, an antigen widely expressed on leukemia and lymphoma cancer cells, B cells and stem cells. Once attached to its target cells, the radioisotope, I-131, emits energy that destroys a patient's cancer cells and bone marrow. If approved, Iomab-B will be used as an induction and conditioning agent prior to bone marrow transplant in patients with relapsed/refractory AML who are at least 55 years old.

The US FDA approves:

Merck KGaA and Pfizer’s Bavencio, or avelumab, for the treatment of patients with metastatic Merkel cell carcinoma (MCC), a rare type of skin cancer. The drug, a fully human anti-PD-L1 IgG1 monoclonal antibody is co-developed by both companies under a 2014 strategic alliance and had accelerated approval process as well as breakthrough status. Avelumab will be the fourth checkpoint inhibitor approved by US authorities and will be listed at a price of $13,000 a month, ahead of payer discounts.

….and Newron’s (Milan, Italy) Xadago, or safinamide, as the first novel treatment of Parkinson’s disease in ten years. The drug has been approved in Europe in 2015 and rejected twice by the FDA for a series of mistakes in the NDA filing. Safinamide is a se­lec­tive mono amine oxidase B (MAO-B) in­hibitor which re­duces “off” time for pa­tients tak­ing lev­odopa, as well as a re­duced rate of dysk­i­ne­sia. The drug works by tar­get­ing  MAO B an enzyme that breaks down dopamine in the brain, al­low­ing for bet­ter re­sults from lev­odopa in con­trol­ling motor func­tions. Xadago will be sold in the US by US WorldMeds, which has a deal with Zam­bon for the com­mer­cial rights.

Just a few days after China FDA director B. Jingquan promised to speed up foreign drug approval at the Chinese Annual Congress, the CFDA has now published a hundred words long document suggesting amendments which will eliminate clinical trial’s hurdles that slow approval. Under the new requirements there will be the possibility to start clinical trials in China without waiting the entering of a phase 2 trial elsewhere as well as filing for a NDA using data from international multicenter trials, so long as those trials include Chinese study sites.

Drugs at clinical stage

The US FDA grants orphan status to ChemoCentryx’s (Moutain View, CA, USA) avacopan as a treatment for the severe kidney disease C3 glomerulopathy characterized by protein deposits into the glomeruli. Avacopan reduces the kidney damage associated with C3G by inhibiting the complement C5a receptor which plays a key role in the inflammatory process

The US FDA grants fast-track designation to Humacyte’s (Research Triangle, NC, USA) Humacyl, a decellularized bioengineered blood vessel regenerative medicine advanced therapy, as treatment for patients with kidney failure who cannot received fistula placement.

Neurocrine Biosciences' (San Diego, CA, USA) Ingrezza, or valbenazine, has met the primary endpoint of a late-stage study in which the drug showed a statistically valid difference from baseline in the AIMS scale than placebo in the treatment of tardive dyskinesia. Valbenazine inhibits a protein called Vesicular Monoamine Transporter 2, which is concentrated in the brain where it plays a key role in the re-packaging and transporting of monoamines (dopamine, norepinephrine, serotonin and histamine) in certain neurons. It modulates dopamine release during nerve communication while exerting minimal impact on other monoamines, thereby minimizing unwanted side effects associated with excessive monoamine depletion, in patients with Tourette, Huntington’s chorea, tardive dyskinesia and schizophrenia. The FDA's PDUFA date for Ingrezza's marketing application is April 11.

Medical Devices and Diagnosis News.

The US FDA approves Medtronic’s latest version of its CoreValve Evolut transcatheter aortic valve replacement (TAVR) for the treatment of severe aortic stenosis in patients too frail for open-heart surgery. This new Evolut PRO valve includes a self-expanding nitinol frame with its supra-annular valve position that helps achieve excellent hemodynamic performance

Nanobiotix (Paris, France) reports that that the Independent Data Monitoring Committee (IDMC) has completed the interim evaluation aimed at evaluating the safety and efficacy of NBTXR3, a first in-class hafnium oxide nanoparticule acting as a radio enhancer, to treat soft tissue sarcoma and has recommended the continuation of the study.  The interim evaluation of the pivotal international  Phase II/III trial, conducted in Europe and in Asia launched in 2014, was based on an analysis of the results of 104 patients out of a total of 156.The completion of recruitment is planned by the end of Q2 2017 and the full data analysis, is expected to be available at the end of 2017. The product is considered as a “device” under European legislation and Nanobiotix expects to receive a CE mark at the end of 2017.

Roche, through Ventana Medical Systems, enters a collaboration with Loxo Oncology (Stamford, CT, USA) to develop a pan-tropomyosin receptor kinase (TRK) immunochemistry (IHC) test to asses which patients are more likely to respond to larotrectinib, a TRK inhibitor developed by Loxo as treatment for various solid tumors.

Agendia (Amsterdam, The Netherlands and Irvine, CA, USA) indicated that its MammaPrint 70-gene signature test that measures risk of recurrence in breast cancer has received the highest medical evidence level 1A label in German Association of Gynecological Oncology (AGO) guidelines for breast cancer care in Germany.

The US FDA warns care providers of a higher rate of cardiac events in patients receiving Abbott’s new bioresorbable Absorb stent compared to those treated with a drug-eluting metal stent.

The Absorb bioresorbable stent props open the affected artery, elutes a drug to reduce inflammation and scar tissue formation, and completely reabsorbs within three years. Image: Abbott

Science & Technology

Scientists at Intermountain Medical Center Heart Institute (Salt Lake City, UT, USA) working with LipoScience Laboratories, have shown that a new biomarker called GlycA can also be used as a predictor of major cardiac events. Like C-reactive protein (CRP) an inflammatory biomarker, GlycA can be detected with blood tests and patients who have high levels of both biomarkers face an even higher risk, according to a press release.

According to new research performed at the University of Aberdeen (Scotland), women who have taken the oral contraceptives seem to have a reduced risk to develop colorectal cancer, endometrial cancer or ovarian cancer than those who have not been on contraceptives. “Because the study has been going for such a long time we are able to look at the very long term effects, if there are any, associated with the pill. What we found from looking at up to 44 years’ worth of data, was that having ever used the pill, women are less likely to get colorectal, endometrial and ovarian cancer”, said Dr Lisa Iversen, research fellow in the Institute of Applied Health Sciences at the University.

Cost, Pricing and Market Access

The UK National Institute for Health and Care Excellence (NICE) has published an updated familial breast cancer guidelines which advocates the use of three medicines to reduce the risk of developing breast cancer. The cost regulator recommends that doctors prescribe either tamoxifen, raloxifene and anastrozole to potentially hundreds of thousands of 'healthy' women who have no personal history of breast cancer but have a higher risk of developing it. According to the guidelines, doctors should offer tamoxifen for five years to premenopausal women at high or moderate risk of breast cancer, unless they have a past history or may be at increased risk of thromboembolic disease or endometrial cancer, and anastrozole for five years to postmenopausal women unless they have severe osteoporosis. Use of anastrozole is a new component of the updated guideline, showing that the drug cut the risk of the disease in post-menopausal women by more than 50 percent in the first five years of use, but with fewer side effects than other preventive options. According to NICE, new evidence demonstrated that if 1,000 women at high risk of breast cancer took anastrozole for five years 35 cases of breast cancer would be prevented, compared to 21 if they took tamoxifen. “The evidence examined by the committee suggests anastrozole will not only reduce the number of breast cancer cases in postmenopausal women compared to tamoxifen, but it is also a more cost effective option. This is good news for women and for NHS budgets,” noted professor Mark Baker, director of the centre for guidelines at NICE. The current NHS list price of anastrozole is £1.19 for 28 tablets.

Eli Lilly says it is cutting an average of 50% off lists prices. After raising list prices an average of 14% in 2016, and dealing with payers, Eli Lilly netted an overall price increase of 2.4%, the company said in a new report, a substantial comedown from 2015, when a 16.3% average increase yielded a net rise of 9.4%.

US President Trump indicated that his administration was working to add pricing legislation to the current healthcare bill. “The cost of med­i­cine in this coun­try is out­ra­geous, many times higher than in some coun­tries in Eu­rope and else­where. Why? Same pill, same man­u­fac­turer, iden­ti­cal and it is many times higher in the United States.You know why? Capaign con­tri­bu­tions. Who knows. But some­body’s get­ting very rich” he said earlier this week in Louisville, Kentucky.

Miscellaneous

Amgen’s Repatha, its PCSK9 cholesterol lowering agent, has shown clear cardiovascular outcomes.  In a study including 27,564 pa­tients over two years. Repatha was able to lower a com­pos­ite of car­dio risks by an av­er­age of 20%, and the im­prove­ment in­creased with time, grow­ing from a 16% risk ad­van­tage in year one to 25% after 12 months. Break­ing down the data, re­searchers noted a 27% re­duc­tion in the risk of heart at­tacks, a 21% risk re­duc­tion for stroke and a 22% re­duc­tion on coro­nary revas­cu­lar­iza­tion. But sig­nif­i­cantly there was no im­pact on mor­tal­ity or un­sta­ble angina.

A real-world study, named CVD-Real, shows that type 2 diabetic patients treated with SGLT-2 inhibitors are at less risk of hospitalization for heart failure and death. The study with records on more than 300,000 patients in six countries finds that SGLT2 medications cut heart failure hospitalization rates by 39% compared with other types of diabetes treatments. The drug class, which includes AstraZeneca’s Farxiga, Eli Lilly and Boehringer Ingelheim’s Jardiance as well as Johnson & Johnson's Invokana, also reduced deaths from any cause by 51%, according to the study.

Sanofi and Regeneron have filed a lawsuit in U.S. District Court in Boston, asking a judge to determine that the two companies don’t infringe on Amgen’s ‘487 patent, which cites IL-4 and IL-13 antibodies. Dupixent, a drug targeted at IL-4 and IL-13, two immune system pathways implicated in allergic diseases, is due to be approved in the US next week. The lawsuit states that the companies had learned that Amgen hired counsel to prosecute infringement of the '487 patent. Amgen confirmed that it believes Dupixent infringes its intellectual property—and that it is ready to litigate. “Amgen does have a patent covering the product, and we will defend our patent rights,” a company spokeswoman said via email.

Bioevents

BIOVISION on April 4-6, in Lyon (France)

Strategic Alliance Management Congress on May 1-3, in Philadelphia (USA)

BIOTrinity on May 8-10, in London (UK)

China BIO Partnering Forum on May 10-11 in Suzhou (China)

9^th Annual China BIO International Partnering Forum on May 31-June 1 in Zhuhai (China)

The Health Industry Sumitt (tHIS) 2017 on May 15-18 in Shanghai (China)

2017 BIO-IT World Conference & Expo on May 23-25 in Boston (USA)

BIO International Convention on June 19-22 in San Diego (USA)

MedFIT on June 28-29 in Grenoble (France)

Nordic Life Science Days (NLS) 2017 on September 12-14 in Malmö-Copenhagen (Sweden and Denmark)

BIOPharm America on September 26-27 in Boston (USA)

BIO Latin America on October 26-28 in Sao Paulo (Brazil)

BIO Europe on November 6-8 in Berlin (Germany)

World Congress on Biomedical Engineering 2017 on November 9-11 in Xian (China)

BIOFIT on November 28-29 in Strasbourg (France)

http://btobioinnovation.com/events/pharma-biotech-events/

http://btobioinnovation.com/events/in-vitro-diagnostic-events/

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