Your guide to the pharmaceutical world Volume 7 Issue 4 Antibiotic Resistance Exposé Resistance is futile Manufacturing Automate, automate, automate Vaccines A shot in the arm Antibiotic Resistance Exposé Resistance is futile Manufacturing Automate, automate, automate Vaccines A shot in the arm www.pbiforum.net 01.qxp_Layout 1 06/08/2019 09:25 Page 1FOR MANUFACTURING IN FOOD, BEVERAGES, PHARMACEUTICALS, TOILETRIES, COSMETICS AND MORE… 1-3 OCTOBER 2019 NEC, BIRMINGHAM THE COMPLETE PRODUCTION LINE EVENT ppmatotalshow.co.uk OWNED & ORGANISED BY FREE TO ATTEND REGISTER NOW 02.qxp_Layout 1 06/08/2019 09:25 Page 1@pbiforumwww.pbiforum.net company/pharma-business-international Contents Volume 7 Issue 4 4 12 24 28 Group Editor: Steve Fisher (s.fisher@blmgroup.co.uk) Editor: Michael Fisher (m.fisher@blmgroup.co.uk) Journalist: Dominic Cuthbert (d.cuthbert@blmgroup.co.uk) Tess Egginton (t.egginton@blmgroup.co.uk) Sales Director: Angie Cooper (a.cooper@blmgroup.co.uk) Sales Manager: Sam Trott (s.trott@blmgroup.co.uk) Sales: Vicky Hunt (v.hunt@blmgroup.co.uk) Tel: +44 (0) 1472 310302 Accounts & Subscriptions: Angela Sharman (a.sharman@blmgroup.co.uk) Design & Production: Gary Jorgensen, Mark Casson, (studio@blmgroup.co.uk) Editorial: Tel: +44 (0) 1472 310305, Fax: +44 (0) 1472 310317 Part of BLMGroup: Armstrong House, Armstrong Street, Grimsby, North East Lincolnshire DN31 2QE England All rights reserved. No part of this publication may be reproduced, transmitted, photocopied, recorded or otherwise without express permission of the copyright holder, for which application should be addressed first to the publisher. While every reasonable care is taken, neither the publisher nor its participating agents accept liability for loss or damage to prints, colour transparencies, negatives or other material of whatever nature submitted to this publication. The views expressed in this publication are not necessarily the views of those held by the publisher. COVER PHOTO: © SHUTTERSTOCK / BILLION PHOTOS News4 Stay up to date with the latest industry updates from the global pharmaceutical technology industry. M&A Round-up8 Regulatory scrutiny has delayed some of the biggest deals in the pharmaceutical M&A space, while other companies seek to strengthen pre-existing pipelines or move into new therapeutic areas. Antibiotic Resistance Exposé12 Without action and serious intervention from healthcare providers, governments and the pharmaceutical and agricultural industries, antibiotic resistance is predicted to kill ten million people every year by 2050. That’s a little over thirty years’ time, but the issue is already having grave consequences in the present. Packaging16 Packaging serves more roles than any other in the pharma industry. Not only is it to attract consumers, but also to relay information, prevent counterfeit goods and keep children from gaining access. Manufacturing20 To remain competitive, reduce costs, meet the stringent standards of regulators and boost productivity and efficiency, pharmaceutical manufacturers must look to innovative digital technologies. Vaccines24 While rising anti-vaccine sentiment and manufacturing scandals plague the news, new innovations are boosting the future of vaccine production and distribution. The Answer to Opioids28 Since the over-prescription of opioids in the United States in the early nineties, the epidemic has gone on to claim the lives of some 400,000 people. PPMA Total Show 201932 Staged every three years, PPMA Total Show (1-3 October 2019, National Exhibition Centre (NEC), Birmingham) is the UK’s largest processing and packaging machinery exhibition. Events34 We give a rundown of pharma events happening around the world. 03.qxp_Layout 1 06/08/2019 09:26 Page 1Cold virus could revolutionise bladder cancer treatment A strain of the common cold virus could potentially revolutionise the treatment of bladder cancer after promising results were discovered by researchers. A study published in Clinical Cancer Research reports that this strain can potentially target, infect and destroy cancer cells in patients with bladder cancer. Researchers from the University of Surrey and Royal Surrey County Hospital investigated the safety and tolerability of exposure to the cancer-killing virus coxsackievirus (CVA21), a naturally occurring strain of the common cold, in fifteen patients with non-muscle invasive bladder cancer. During this study the patients received CVA21 via a catheter in the bladder one week prior to prescheduled surgery to remove their tumours. Examination of tissue samples post-surgery discovered that the virus was highly selective, targeting only cancerous cells in the organ and leaving all other cells intact. The virus was found to have infected cancerous cells and replicated itself causing the cells to rupture and die. 4 Pharma Business International www.pbiforum.net Latest news SICK launches hygienic stainless-steel safety light curtain With a hygienic stainless-steel housing exclusively developed to meet stringent pharmaceutical industry requirements, the SICK TWINOX4 safety light curtain is resistant to aggressive cleaning and decontamination regimes. The TWINOX4 is a Type 4 device (IEC 61496-1) with 14mm beam resolution and can be used in safety applications requiring PLe (EN ISO 13849) and SIL3 (EN 62061). The safety light curtain protects operating personnel when interventions are required in the hazardous areas around machines that are subject to stringent hygiene requirements. It is ideal for use in Restricted Access Barrier System areas such as primary packing and filling stations. Rugged, resistant to harsh cleaning media and designed without edges or gaps, the TWINOX’s elegant, 20 mm x 40 mm cross-section dimensions make it particularly suitable for integration in pharmaceutical machinery when space is limited. To find out more, visit www.sick.com. Researchers develop ‘genomic barcode tracker’ for immune cells A new method has been developed to spot rare immune cells that are reactive against cancer cells from within a patient’s own immune system. Developed by researchers from the Garvan Institute of Medical Research in Australia, the patented ‘RAGE-seq’ method enables scientists to track how immune cells evolve inside tumour tissue for the first time. This, they say, reveals unprecedented insight into how to better arm the immune system to target cancer. The technique, described in Nature Communications , can be likened to a barcode tracker, able to scan detailed information from thousands of immune cells at a time. “This method gives us the most detailed view yet of how immune cells behave in the human body,” says Professor Chris Goodnow, Executive Director of the Garvan Institute and co-senior author of the published work. “Immune cells play a critical role in the development of disease. This method shows significant potential to help us personalise cancer treatments to the individual.” © Shutterstock / Natali_ Mis © Shutterstock / Pazargic Liviu 04-07.qxp_Layout 1 06/08/2019 09:27 Page 1Pharma invests £377m in UK R&D collaborations The pharmaceutical industry continues to invest significantly in UK research and development, according to new figures from the Association of the British Pharmaceutical Industry (ABPI). The data published on Disclosure UK shows that the industry spent £377.3 million on collaborations relating to R&D activities in the UK during 2018 – an increase from £370.9 million in 2017 – signalling the strength of the sector through a period of economic uncertainty. Disclosure UK is the pharmaceutical industry-led database of payments and benefits in kind made to UK healthcare professionals (HCPs) and organisations (HCOs). It was introduced to increase transparency about collaborations between individual doctors and organisations – including NHS Trusts – and pharmaceutical companies. The 2018 figures show that £508.1 million has been disclosed by pharmaceutical companies for 2018, compared with £499.3 million in 2017. £377.3 million of this was spent on R&D collaborations with HCPs and HCOs, compared with £370.9 million in 2017. Pharma Business International 5 www.pbiforum.net Latest news J&J launches research consortium to help end TB Johnson & Johnson has launched an international research consortium to discover and develop new tuberculosis (TB) antibiotics. Working in collaboration with eight European academic and biotech partners, J&J said the move is the first in a series of new collaborations to advance TB research and development. The initiative – called RESPIRI-TB – is co-funded by Europe’s Innovative Medicines Initiative (IMI) and Janssen Pharmaceutical. The goal is to help enable the development of a new, more efficient combination drug regimen to cure multidrug-resistant TB, with a focus on shortening treatment duration and minimising the likelihood of resistance. The partners will work to advance the discovery and early-stage development of new compounds from different drug classes that could be used – in combination with each other or with existing therapies, such as Janssen’s bedaquiline (the first novel TB medicine to be approved in more than 40 years). Merck & IBM part of FDA blockchain programme IBM and Merck are among the companies collaborating as part of the FDA’s programme to evaluate the use of blockchain to protect pharmaceutical product integrity. The programme, in support of the US Drug Supply Chain Security Act (DSCSA), also includes KPMG and Walmart. It aims to address the requirements to identify, track and trace prescription medicines and vaccines distrusted within the US. The programme is intended to assist drug supply chain stakeholders – including the FDA – in developing the electronic, interoperable system that will identify and trace certain prescription drugs as they are distributed within the US. The proposed network is intended to help reduce the time needed to track and trace inventory; allow timely retrieval of reliable distribution information; increase accuracy of data shared among network members; and help determine the integrity of products in the distribution chain, including whether products are kept at the correct temperature. © Shutterstock / NicoElNino © Shutterstock / Linda Bestwick © Shutterstock / create jobs 51 04-07.qxp_Layout 1 06/08/2019 09:27 Page 26 Pharma Business International www.pbiforum.net Latest news Anticancer drug disguises itself as fat to combat tumours A stealthy new drug-delivery system disguises chemotherapeutics as fat in order to outsmart, penetrate and destroy tumours, new studies show. Essentially, tumours invite the drug inside thinking they are fats. Once there, the targeted drug activates, immediately suppressing tumour growth. “It’s like a Trojan horse,” said Northwestern University’s Nathan Gianneschi, who led the research. “It looks like a nice little fatty acid, so the tumour’s receptors see it and invite it in.” To develop the targeting system, Gianneschi and his team engineered a long-chain fatty acid with two binding sites able to attach to drugs on each end. The fatty acid and its hitchhiking drugs are then hidden inside human serum albumin (HSA), which carries molecules, including fats, throughout the body. The body’s cellular receptors recognise the fats and proteins supplied by the HSA and allow them inside. Quick-growing and hungry, cancer cells consume the nutrients much faster than normal cells. When the cancer cells metabolise the hidden drug, they die. Gilead & Galapagos enter R&D collaboration Gilead Sciences and Galapagos have entered into a 10-year global research and development collaboration. The agreement sees Gilead gain access to an innovative portfolio of compounds, including six molecules currently in clinical trials, more than 20 preclinical programs and a proven drug discovery platform. Galapagos will receive a $3.95 billion upfront payment and a $1.1 billion equity investment from Gilead. It will use the proceeds to expand and accelerate its R&D programmes. Gilead will receive an exclusive product license and option rights to develop and commercialise all current and future programs in all countries outside Europe. In addition, Gilead and Galapagos have agreed to amend certain terms in the agreement governing filgotinib, the candidate being advanced for rheumatoid arthritis and other inflammatory diseases to provide a broader commercialisation role for Galapagos in Europe. The collaboration will allow for closer scientific partnership between the companies. Evotec spin-out developing DNA damage response portfolio Germany’s Evotec and a venture capital consortium have formed a spin-off company developing its DNA damage response portfolio. This portfolio comprises discovery-stage assets and drug targets that promise broad therapeutic application in a variety of cancers. Breakpoint Therapeutics’ mission is to develop first and best-in- class oncology drugs that interfere with DNA repair and replication stress pathways to facilitate the cure of therapy-resistant cancers. The new company will initially focus on advancing multiple drug discovery programmes initiated at Evotec that address high unmet medical needs of different patient groups. The goal of the spin-off is to accelerate early projects through discovery and pre-clinical development and expect to deliver the first IND-ready drug in 2022. The early stage funding amounting to €30 million will be covered by an international investor consortium led by Medicxi, a life sciences-focused investment firm; Taiho Ventures, the venture capital arm of Taiho Pharmaceutical, and Evotec. Evotec will hold below 50% of the company. © Nathan Gianneschi/Northwestern University © Shutterstock/Billion Photos © Shutterstock / alice-photo 04-07.qxp_Layout 1 06/08/2019 09:27 Page 3 EUROPE Dacomitinib recommended for use on NHS NICE has recommended Dacomitinib for use on the NHS as a first-line treatment option for people with a type of non-small-cell lung cancer (NSCLC). This once-daily pill will be available on the NHS for adults with locally advanced or metastatic NSCLC who have tested positive for the epidermal growth factor receptor mutation. This is a change from the committee’s initial decision which found dacomitinib to not be a cost-effective use of NHS resources. ViiV picks up EU nod for two-drug HIV treatment ViiV Healthcare has picked up European marketing authorisation for Dovato for treating HIV-1 in adults and adolescents over 12. Dovato (dolutegravir/lamivudine) is a new once-daily single pill two-drug regiment for treating HIV-1 infection. The authorisation is supported by data from the landmark global GEMINI 1 & 2 studies that included more than 1,400 HIV-1 infected adults. Dovato was authorised by the US FDA in April 2019. Europe approves only once-daily PARP inhibitor Talzenna has become the only once-daily PARP inhibitor approved in Europe for hereditary breast cancer. Specifically, the oral poly polymerase inhibitor has been approved by the European Commission as monotherapy for treating adult patients with inherited BRCA-mutated locally advanced or metastatic breast cancer. The approval is based on results from the EMBRACA trial – the largest Phase 3 study of a PARP inhibitor in gBRCA-mutated, HER2- LA or MBC. Green light for Ultomiris for treating PNH Ultomiris, the first and only long-acting C5 complement inhibitor administered every eight weeks, has been approved in Europe for treating adult patients with paroxysmal nocturnal haemoglobinuria (PNH). The approval is based on comprehensive results from two Phase 3 studies, the largest Phase 3 program ever conducted in PNH. Ultomiris was approved in the US in December 2018 and in Japan in June 2019. UNITED STATES First & only nuclear export inhibitor approved in US US approval has been granted to Karyopharm Therapeutics’ Xpovio in combination with dexamethasone for treating adult patients with relapsed or refractory multiple myeloma. The decision from the FDA means that Xpovio (selinexor) is currently the first and only nuclear export inhibitor approved in the US. Investigational sickle cell medicine filed by FDA The FDA has accepted Novartis’ Biologics License Application (BLA) and granted Priority Review for the investigational sickle cell medicine crizanlizumab (SEG101). If approved, crizanlizumab is expected to represent the first monoclonal antibody targeting the P-selectin mediated multi- cellular adhesion in sickle cell disease. Novartis submitted the application for crizanlizumab for the prevention of vaso- occlusive crises in patients with sickle cell disease and was granted Breakthrough Therapy designation in December 2018. Avastin biosimilar approved in US Pfizer’s oncology biosimilar to Avastin has been approved in the US for treating five types of cancer. Zirabev can now be used to treat metastatic colorectal cancer; unresectable, locally advanced, recurrent or metastatic non- squamous non-small cell lung cancer; recurrent glioblastoma; metastatic renal cell carcinoma, and persistent, recurrent or metastatic cervical cancer. The approval was based on review of a comprehensive data package which demonstrated biosimilarity of Zirabev to the reference product. Botox approved for upper limb spasticity Regulators have expanded the indication of Allergan’s Botox to treat paediatric patients with upper limb spasticity. An expanded indication to cover lower limb spasticity in paediatric patients is also under review. A decision is expected in Q4 2019. The latest approval of Allergan’s supplemental biologics application, follows a six-month Priority Review by the FDA. www.pbiforum.netPharma Business International 7 04-07.qxp_Layout 1 06/08/2019 09:27 Page 4M&A ROUND-UP 8 Pharma Business International www.pbiforum.net B efore checking in with the latest on the proposed merger between Bristol-Myers Squibb (BMS) and Celgene, let us first address the $63 billion elephant in the room. In one of the biggest headline-grabbing acquisitions of the year (so far), AbbVie is acquiring Allergan, the Irish-headquartered makers of Botox. The deal provides the $32.7 billion turnover biopharmaceutical company with “immediate scale and profitability”. That’s for its existing growth platform, but the deal also provides several other attractive growth platforms alongside leadership positions which the company says diversifies and expands its revenue base. Perhaps most importantly, certainly as far as AbbVie are concerned, is that the acquisition will result in significant cash flow generation. In 2018, for example, the combined companies generated $19 billion in operating cash flow. Together, they look set to rival the industry’s biggest players, potentially changing the lay of the market – something that AbbVie Chairman and CEO Richard A. Gonzalez is invested in. “This is a transformational transaction for both companies and achieves unique and complementary strategic objectives,” he said. Now, back to that $74 billion merger deal. The latest step forward, at least at the time of writing, came towards the end of June. In a bid to expedite the merger, BMS is divesting psoriasis treatment Otezla (apremilast). In a company update, BMS said that it remains “actively engaged” in discussions with the US Federal Trade Commission (FTC) on the regulator’s continued review of the proposed merger. According to the company, the divestment will allow the merger to close “on a timely basis in light of concerns expressed by the FTC”. The divestiture is subject to a further review by the FTC and requires that BMS enter into a consent decree. Once the FTC accepts the consent order and the other customary closing conditions are satisfied, BMS says that it intends to close the Celgene transaction “at the earliest possible date”. Right now, that means the end of 2019 or the beginning of 2019. We’ll see how the situation lies in next issue’s round- up. Pfizer has taken another step forward in the ongoing process of strengthening its oncology pipeline with the $11.4 billion acquisition of Array BioPharma. Based in Boulder, Colorado, Array is a commercial stage biopharmaceutical company focussed Under scrutiny Regulatory scrutiny has delayed some of the biggest deals in the pharmaceutical M&A space, while other companies seek to strengthen pre-existing pipelines or move into new therapeutic areas. 10 Á 08-11.qxp_Layout 1 06/08/2019 09:29 Page 1© Shutterstock /Syda Productions 08-11.qxp_Layout 1 06/08/2019 09:29 Page 2Next >