< PreviousM&A ROUND-UP 10 Pharma Business International www.pbiforum.net on the discovery, development and commercialisation of targeted small molecule medicines to treat cancer as well as other diseases of high unmet need. For Pfizer, this means it gets access to an innovative and lucrative portfolio of medicines which includes the approved combined use of Braftovi (encorafenib) and Mektovi (binimetinib) for the treatment of BRAFV600E or BRAFV600K mutant unresectable or metastatic melanoma. Pfizer said this combination therapy has “significant potential” for long-term growth. “The proposed acquisition of Array strengthens our innovative biopharmaceutical business, is expected to enhance its long-term growth trajectory, and sets the stage to create a potentially industry-leading franchise for colorectal cancer alongside Pfizer’s existing expertise in breast and prostate cancers,” said CEO Albert Bourla when the deal was announced back in June. It’s been a busy period for Pfizer on the M&A front with the New York pharma giant having recently completed its acquisition of Swiss biotechnology company Therachon. Breaking down the deal, Pfizer paid $340 million up front with additional payments of up to $470 million depending on certain key milestones in the development and commercialisation of TA-46 – an investigation medicine for treating achondroplasia. All in all, the deal could © Shutterstock /AlexLMX 08-11.qxp_Layout 1 06/08/2019 09:29 Page 3Pharma Business International 11 www.pbiforum.net M&A ROUND-UP be worth up to $810 million. While Pfizer has been taking pragmatic steps to bolster its biopharmaceutical business, this deal sees the company reinforce its Rare Disease team and address significant unmet medical needs. For example, there are currently no approved treatment options for achondroplasia, a genetic condition and the most common form of short-limb dwarfism. And according to Seng Cheng, Senior Vice President and Chief Scientific Officer of Pfizer’s Rare Disease Research Unit, TA- 46 has “the potential to be c first-in-class therapy for the treatment of achondroplasia”. There’s been extensions on top of delays for Roche’s $4.3 billion acquisition of Spark Therapeutics which was originally announced back in February. The delay began in early June after the FTC asked both parties for additional information and documentary material to support its review of the deal in the second example of increased FTC scrutiny in the pharma M&A space. Merely a month later, the two companies announced that they have mutually extended the deadline to conclude the deal by three months, taking the slated closure to April 30 2020. At the lower end of the billion-dollar deals is Merck bolstering its own oncology pipeline with the $2.20 billion swoop for Texan company Peloton Therapeutics. Broken down, the deal sees Merck make an upfront payment of $1.05 billion via a subsidiary, while Peloton shareholders are eligible to receive a further $1.15 billion depending on future regulatory and sales milestones. For Roche, the deal is motivated by a strategy to pursue novel therapeutic candidates and grants it access to Peloton’s lead candidate, PT29777 – a novel oral HIF-2 a inhibitor in late-stage development for renal cell carcinoma. Lastly this issue, there’s Catalent’s $1.2 billion acquisition of Paragon Bioservices, a viral vector development and manufacturing partner for gene therapies. Unsurprisingly, the deal gives Catalent a foothold in the fast-growing gene therapy field where many of its industry peers are moving into via M&A strategies. Breaking As this issue was being written, news broke that Pfizer is combining Upjohn, its off-patent branded and generic medicines business, with Mylan to create a new pharmaceutical company. Pro forma 2020 revenues are expected to be between $19 billion to $20 billion. 08-11.qxp_Layout 1 06/08/2019 09:29 Page 4ANTIBIOTIC RESISTANCE EXPOSÉ 12 Pharma Business International www.pbiforum.net A study from the European Centre for Disease Prevention and Control (ECDC) found that some 33,000 people in the European Union and European Economic Area die every year because of infections with antibiotic-resistant bacteria. What’s more, seventy-five per cent of this burden is due to infections that are picked up in hospital settings, putting the onus as much on healthcare providers and hospitals, as regulators and the pharmaceutical industry. Antimicrobial resistance (AMR) isn’t only one of the most pressing health issues facing humanity, but one of the most profound threats of our times, right up there with environmental disaster, water shortages and world hunger. Ineffective antibiotics won’t only open the floodgates to so- called ‘superbugs’, but will also mean that routine operations such as caesarean, hip replacements and appendectomies could become too dangerous to perform, effectively resulting in a new dark age. Earlier this year, the UK published a twenty-year vision alongside a five-year national action plan to contain and control AMR by 2040. The specifics of this approach include cutting the number of drug resistant infections by ten per cent by 2025; reducing the use of antibiotics in humans by Resistance is futile 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. 12-15.qxp_Layout 1 06/08/2019 09:29 Page 1ANTIBIOTIC RESISTANCE EXPOSÉ Pharma Business International 13 www.pbiforum.net © Shutterstock /Bukhta Yurii fifteen per cent and preventing at least 15,000 patients from contracting infections as result of their healthcare each year by 2024. The major focus will be on ensuring current antibiotics remain effective by reducing the number of resistant infections and supporting clinicians to prescribe properly. This is particularly prudent as data from government agency Public Health England shows that at least twenty per cent of all antibiotics prescribed in primary care in England are inappropriate. This must be reduced to at least ten per cent in order to achieve the national aims outlined in the AMR plan. The data also shows that in almost a third of all prescriptions, no clinical reason was documented. There needs to be a fundamental shift in GPs and healthcare providers in how prescriptions are handled. There are encouraging signs, however, with data showing that antibiotics prescribing in England has reduced by five per cent since 2012. The danger isn’t only in the antibiotics 14 Á © Shutterstock / funnyangel 12-15.qxp_Layout 1 06/08/2019 09:29 Page 2ANTIBIOTIC RESISTANCE EXPOSÉ that are prescribed in healthcare settings, but those we consume through meat products. A key approach of the AMR plan also includes animal health. Animals reared for food, particularly in intense farming practices, are given antibiotics to fend off diseases as a precautionary measure, whether they are sick or not. But doing so has flooded the food chain with antibiotics. Data from the World Health Organisation reveals that the total amount of antibiotics used in animals is four times higher than that of humans. To help combat this, the Government has committed to working with vets and farmers to further reduce antibiotic use in animals by twenty-five per cent until 2020 with the objectives set to refresh in 2021. A big part of the issue is financial and so the battle against AMR must address current funding models. The National Institute for Health and Care Excellence (NICE) and NHS England are together exploring a new payment model that pays pharmaceutical companies based on how valuable their medicines are to the NHS rather than the flawed current model on the quantity of antibiotics sold. As explored in our feature on the opioid crisis (page 28), there is a precedent for pharmaceutical companies providing doctors with gifts and financial incentives to over-prescribe and write scripts for certain medicines over others. The financial approach also means providing funding to develop efficient alternatives to antibiotics. A recent tranche of funding saw ten centres across England receive capital from the Department of Health and Social Care. Among those was Manchester University NHS Foundation Trust who secured £4.4 million to further its research into individualised approaches to antibiotic prescribing by bringing together patient care and clinical research. That basically means that patients will be given the right antibiotic at the right dose for the right duration. That last one is particularly pressing as patients are encouraged to finish their entire prescription of antibiotics regardless of whether they still need them. Across the pond, research from the University of Wisconsin-Madison has repurposed the gene editing tool CRISPR to study and improve pre- existing antibiotics and develop new ones. Knowing as mobile-CRISPRi, the technique reduces the production of protein from targeted genes, allowing researchers to identify how antibiotics inhibit the growth of pathogens. In what might be the most left-field solution, researchers at Massachusetts Institute of Technology (MIT) have explored the antimicrobial properties of wasp venom to create a potent peptide against bacteria that, they say, is safe for human cells. Typically, the compounds found in wasp venom is toxic for humans – as anyone who’s ever been stung can attest – rendering them unusable as antibiotic drugs. However, using mouse models, the researchers found that their strongest peptide could completely eliminate Pseudomonas aeruginosa – a strain of bacteria that causes respiratory and other infections and is resistant to most antibiotics. Antimicrobial resistance is one of the greatest threats facing humanity. Over-prescribing and intensive farming practices have resulted in a dangerous epoch that has already claimed the lives of tens of thousands of people. With rigorous and wide- reaching plans in place, and innovative alternatives being developed, we may yet avert catastrophe. 14 Pharma Business International www.pbiforum.net 12-15.qxp_Layout 1 06/08/2019 09:29 Page 3Pharma Business International 15 www.pbiforum.net ANTIBIOTIC RESISTANCE EXPOSÉ © Shutterstock /i viewfinder 12-15.qxp_Layout 1 06/08/2019 09:29 Page 4PACKAGING 16 Pharma Business International www.pbiforum.net 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. T here surely can’t be a faster moving sector in the pharmaceuticals industry than packaging. Success is driven by innovation, which is itself driven by the need for products to give across more information than ever before, remain totally secure throughout and also shrink the carbon footprint as much as possible. In many markets, government regulations are already stipulating the traceability of pharmaceutical packaging or will do so in the near future. Hence, packaging needs to be engineered for increased strength, using less material, and always taking into account the cost element. This has led to major overhauls of the packaging process in many companies – and some find this a challenge. Proof in the packaging Proof in the packaging 16-19.qxp_Layout 1 06/08/2019 09:31 Page 1Pharma Business International 17 www.pbiforum.net PACKAGING © Shutterstock /Yoottana Tiyaworanan Manufacturers can spend a lot of money to be theoretically compliant and then through simple operational or product changeover errors do something like putting the wrong label on the package. When there are multiple changeovers, short batch runs and often a large product portfolio to manage, there are certainly many potential flashpoints. For several years it’s been possible to completely automate the remote setting up of date code and barcode scanners, ensuring the label is correct, and correctly applied, right first time, every time. To virtually eliminate the operator risk, such systems, as one might expect, are not cheap, but compared with the risk of batch rejection, rework, scrap, fines for non-compliance and upset customers, this automation should be seen as a manufacturing necessity. Consumer demand and changes in how people use pharmaceutical products, leading to a rise in smaller size packs, has also driven innovation in the packaging sector and this means there has been a rapid growth in thin walled packaging, mostly for injection moulding 18 Á 16-19.qxp_Layout 1 06/08/2019 09:31 Page 2PACKAGING 18 Pharma Business International www.pbiforum.net and thermoforming applications. A lower moulding weight certainly means significant reductions in material and shipping costs. Stackability of containers is another benefit, while more product can be stacked into transportation vehicles. Thin walling also allows for faster cycle times compared to thicker walled plastic parts. Packaging also has a larger role to play in anti-counterfeit measures than many other aspects of the supply chain. With bootleg or counterfeit pharmaceutical products being a multi-billion pound black market, there is a need to crack down on it where possible. Counterfeit- proof packaging is one such approach, with seals and locks to show a consumer when something has already been opened. But there are other aspects to keep in mind, namely that as the industry becomes more proficient – so too do those operating on the illegal side of things. Authorisation signs such as hologram stamps can be harder to mimic, but it’s important that the consumers know to look for these – otherwise there isn’t going to be any benefit. One way to draw attention to it is through marketing – perhaps with some kind of “always look for the stamp” campaign to draw attention to the threat. Visible holograms with company logos, combinations of letters and digits, instantly identify the blister packs as © Shutterstock /Brian Balster 16-19.qxp_Layout 1 06/08/2019 09:31 Page 3Pharma Business International 19 www.pbiforum.net PACKAGING originals. Invisible codes that can be verified quickly and easily can also be incorporated into the hologram. All that is required for verification of a hidden logo or data matrix code is a simple laser pointer. The challenges over the next few years to make sure all packaging is compliant will likely concentrate minds throughout the sector. Happily, the industry is offering a host of flexible and innovative solutions to allow changes to be implemented as smoothly as possible. © Shutterstock /pavelgr 16-19.qxp_Layout 1 06/08/2019 09:31 Page 4Next >