< PreviousRESEARCH & DEVELOPMENT10Pharma Business International www.pbiforum.net© Shutterstock / Sk ElenaBreakthrough From the ‘death sentence’ ofthe 1980s to near-normal lifeexpectancy today, researchinto HIV and AIDs is makinghuge headway. 10-13_Layout 1 09/06/2017 13:30 Page 1Pharma Business International 11www.pbiforum.netRESEARCH & DEVELOPMENTHIV marked the end of an era. Gonewas the free love of the sixties; now sexwas the demon. The distressingadvertising and public announcementcampaigns that followed in the wake ofthe AIDs epidemic of the 1980s gave riseto profound fears around sex, particularlytowards homosexual men. For thatreason, the disease has so oftenbeen associated in the samebreath as homophobia. Itsother connotation, of course, is withpoverty. The disease is epidemic acrossparts of Africa where children arefrequently born infected. A staggering number of those infectedlost their lives to the disease. Publicawareness skyrocketed after the death ofQueen frontman Freddie Mercury put afamous face on and humanised thedisease. Ongoing efforts to understand,disarm and manage AIDs have led tosome remarkable developments. Forpeople who started treatment after 2008,life expectancy is now near-normal. Thisis a far cry from the death sentencerhetoric that so often accompanied thedisease some four decades ago. TheAIDs and HIV R&D space is an area ofcontinuous innovation and has heralded anumber of breakthroughs this yearalone. GSK and ViiV Healthcare - theglobal specialist HIV companymajority-owned by GSK, withPfizer and Shionogi asshareholders - hassubmitted regulatoryapplications for the first HIVmaintenance regimen12 Á© Javier Guenaga10-13_Layout 1 09/06/2017 13:30 Page 2RESEARCH & DEVELOPMENT12Pharma Business Internationalwww.pbiforum.netcomprised of only two medicines. Thesubmissions are based on the SWORDstudies that included more than onethousand patients who previouslyachieved viral suppression on a three- orfour-drug antiretroviral regimen.Use of dolutegravir and rilpivirine as atwo-drug regimen for HIV-1 maintenancetherapy is investigational and notapproved anywhere in the world. Typicallya regimen of three or more drugs is usedto maintain HIV viral suppression but, asViiV argue, it’s important to question andshake up the status quo. “We believed that dolutegravirwould have the right profile to be acore agent in a two-drugregimen. Data from the SWORDstudies supported ourhypothesis that a two-drugregimen of dolutegravir andrilpivirine could maintain viralsuppression and theseregulatory submissions markwhat may be a step change inHIV treatment,” says John CPottage, Jr, MD, Chief Scientificand Medical Officer, ViiVHealthcare.An important step forward hasalso been made in theadvancement of HIV vaccinedisease at The Scripps ResearchInstitute (TSRI). The development waspossible thanks to previous studies atTSRI showing the structures of a proteinon HIV’s surface, called the envelopeglycoprotein.The scientists used these structures todesign a mimic of the viral protein from adifferent HIV subtype, subtype C, whichis responsible for the majority ofinfections worldwide. The newimmunogen is now part of a growinglibrary of TSRI-designed immunogensthat could one day be combined in avaccine to combat many strains of HIV. HIV mutates rapidly, so there arecountless strains of HIV circulating© Shutterstock / Jarun Ontakrai10-13_Layout 1 09/06/2017 13:30 Page 3Pharma Business International 13www.pbiforum.netRESEARCH & DEVELOPMENTaround the world. Of these strains,scientists tend to focus on the mostcommon threats – called clades A, B andC. Like a flu vaccine, an effective HIVvaccine needs to protect against multiplestrains, so researchers are designing aset of immunogens that can be givensequentially or as a cocktail to people sotheir immune systems can prepare forwhatever strain they come up against.Researchers are also moving closer tofully curing the disease, after a team fromthe University of Pittsburgh’s GraduateSchool of Public Health developed aquicker, easier, less expensive, and moreefficient way of checking whether or notHIV is still hiding in CD4 cells. The newtest can detect more efficiently the HIVreservoir that continues to stay hidden inthe body’s CD4 cells, which are shown inthis picture.The greatest challenge in coming upwith a cure for HIV is detecting the virusafter retroviral therapy. HIV can hide inimmune cells at levels that are hard toidentify. Current anti-HIV therapysuppresses the infection to a nearundetectable level, but the virus canpersist in a dormant form in CD4 T cells.However, most of the HIV DNA in thesecells is defective and cannot causeinfection.Though HIV and AIDs don’t have thesame relationship with the public as oncethey did, innovation remains consistentlyhigh. The above breakthroughs show thatare understanding of these diseases isstill unfolding, helping pave the way forway for simple, lasting and effectivetreatment for all. © Shutterstock / Kateryna Kon10-13_Layout 1 09/06/2017 13:30 Page 4ACCURACY & MEASUREMENT14Pharma Business International www.pbiforum.netThe burdens that accompany clinical trial participation have been widelydocumented. There has been mounting evidence suggesting that asignificant proportion of findings during trials are not even reported, leadingmany to question their place, if not the way they are organised and managed. Travelling to trial sites, as well as complying with medication regimes andundergoing procedures, all serve to put strains on patients. This leads somepeople to drop out, while others simply do not comply with the protocol. Ineach instance, the subsequent data can be skewered, compromised or leavea company needing to start from scratch or abandon the trial altogether. What is changing, however, is the willingness of sponsors to redesign theirstudies around patients and recognising that this system is in everyone’sbest interest. These shifting attitudes are underpinned by growing evidencethat the current system is flawed. According to a recent survey of 3,150people by the Centre for Information and Study on Clinical ResearchParticipation, more than one fifth of trial subjects find the experiencesomewhat or very stressful. Doubtless, this has some bearing on the resultsof test medications and treatments. When asked what they liked least aboutthe experience, respondents cited the location of the medical centre, thetime consuming nature of study visits, and the cumbersome procedures theyhad to follow. The consequences of these experiences extend beyond patients.Sponsors need people to want to enrol in trials and take their medication perprotocol if they are to gather high-quality data as fast as possible. Yet, trialsdesigned without considering the needs of patients are unlikely to achieveoptimal enrolment, retention and compliance rates. This status quo needsshaking up to serve the best interest of sponsors and patients alike. Recognising this, sponsors are increasingly building the patientperspective into all aspects of their clinical trials.Clinicalefficiency The growing need for clinical trials to meet the requirements of regulators,deliver consistently high-quality data, and come in on budget has led tostudy designs that prioritise timeliness and convenience, yet often at thedetriment of patients. Priorities are changing, though, as sponsors realisestudies designed with patients in mind are also to the benefit of otherstakeholders. This has led to the rise of patient-centric clinical trials. 16 Á14-16_Layout 1 09/06/2017 13:31 Page 1Pharma Business International 15www.pbiforum.netACCURACY & MEASUREMENT© Shutterstock / spreewald.picture.de14-16_Layout 1 09/06/2017 13:31 Page 2ACCURACY & MEASUREMENT16Pharma Business International www.pbiforum.netPharma BusinessInternational:What doespatient centricity mean in thecontext of clinical trials?Justin Schroeder:Patientcentricity is an industrybuzzword right now garnering alot of attention in thepharmaceutical community.Frankly, it means a lot ofdifferent things to a lot ofdifferent people. Specificallywithin the clinical trialcommunity, we’re seeing peopletaking a step back from thetraditional thinking of what’smost cost-effective or mostimmediate and really looking atthe broader perspective ofwhat’s most effective for thepatient. As they’re starting torevaluate that, they’re realizingthat focusing on the patientultimately leads to a lot ofadditional benefits that faroutweigh the short term costimplications or perception that itmay lengthen critical lead times.PBI:What sort of benefits cancompanies realise through patientcentricity?JS:Patient centricity leads to morefocused clinical trials with betterparticipant retention, better engagementwith the study, and better adherence tothe medication and protocol. Keepingmore patients in a trial and them takingtheir treatments as per the protocol cansignificantly cut the time it takes tocomplete a study and improve the qualityof the data it generates. These are hugebenefits that substantially outweigh anyconsiderations of short-term costadvantages of running less patient-centric trials.PBI:What role can packaging play inmaking trials more patient centric?JS:A lot of people have traditionallygone for the most convenient way todeliver a product to the patient. This isnot necessarily the most effective way todeliver a product to the patient. A bottleis a great example. A bottle providesconvenient protection for tablets duringdelivery, but such simple packaging isnot most effective for patients.Instead, companies can use packagingto increase adherence. Packaging thatprovides medication in a calendarizedunit dose format shows patients exactlyhow they’re supposed to take it on thatparticular day, or that morning, evening,with or without food, et cetera.When utilizing complianceprompting packaging, it’s verywell laid out for them so theycan track their progress andkeep to the regimen.PBI:What do companiesneed to consider whenplanning direct-to-patientstudies?JS:Not much changes from apackaging and labellingperspective. The bigger changesare on the distribution side,particularly with biologics thatneed to be kept in a coldenvironment. You need to makesure you have a robust modelthat ensures products are in acold-chain environment all theway to the patient’s home andthat the infrastructure is in placeto keep them refrigerated oncethey reach their destination.Also, patients need to be well-educated in how to use theproduct.PBI:More broadly, how cancompanies maintain their focus onpatient centricity?JS:It will take a fundamental mindsetshift for the industry to make sure that atevery step they keep the patient’sinterests at the highest level. Sometimesthat mindset will create inconveniencesfor the people administering the study oradd additional costs in the short-run.Over a longer time frame, the benefitsand financial impact far outweigh any ofthe short-term costs. There’s a lot ofvalue to be gained for sponsorcompanies, CROs, and suppliers inmaking sure they keep patients’ interestsfront and centre.Sponsors that take the time to design patient-centric clinical trials are rewarded with significant mid- to long-termbenefits, according to Justin Schroeder, PCI Pharma Services. Here, Schroeder discusses the benefits of patient-centricclinical trials, the role packaging can play, and why it is worth incurring up-front costs and inconveniences to put thepatient at the centre of studies.14-16_Layout 1 09/06/2017 13:31 Page 3Pharma Business International 17www.pbiforum.netSECURITYIf, as physics dictates, there is anequal and opposite reaction to everyaction, then we can also assume that forevery legitimate medicine, there exists acounterfeit. A black market has grownaround the production, transportationand sale of counterfeit medicines. Withthe advent of home broadband and laterthe proliferation of smart phones, it’s noweasier than ever to purchase phonydrugs. Consumers can be driven tocounterfeits for a number of reasons,with affordability chief among them. Theymight also seek to indulge a drug habit,as witnessed in the chronic opioid crisisin the United States.Despite often being cheaper than theircounterparts, counterfeit medicines posea safety nightmare. As they are notbeholden to a regulatory body, theseproducts could contain widely differentamounts of active ingredients. This putspatients in danger of overdosing. In the ongoing battle againstcounterfeits, pharmaceutical companieshave had to take their packaging back tothe drawing board. Demand for saferpackaging is on the rise, with the latest© Shutterstock / Sherry Yates YoungSafe and secure Safer packaging is helping to stem the rising tide of counterfeit medicines flooding the market. 18 Á17-19_Layout 1 09/06/2017 13:31 Page 1SECURITY18Pharma Business International www.pbiforum.netforecasts predicting a 12.1 per cent spikebetween 2016 and 2026. More than 30 per cent of totalpharmaceutical products in developingmarkets are counterfeited andapproximately 15 per cent drugs soldacross several sales channel indeveloped markets are fake. Therampant counterfeiting of drugs haspushed pharma producers to opt forsecure solutions. Anti-counterfeitingpackaging is one of the measures thatpharma majors are relying on. However, with advancements intechnology, manufacturers are alsointegrating new and innovative optionswith conventional solutions such asintegrating authentication overt featureswith covert elements, forensics, andtrack & trace elements. These measureshave translated into fruitful results forpharmaceutical companies and tier IIpharma companies also prefer similarapproaches. These effective measuresconsidered by pharma companiesresulted in the sudden increase indemand for anti-counterfeitpharmaceutical packaging across theglobe.Innovation in the packaging segment isheralding some robust results. Some ofthe most common examples of anti-© Shutterstock / Image Point Fr17-19_Layout 1 09/06/2017 13:31 Page 2SECURITYPharma Business International 19www.pbiforum.netcounterfeit measures are advancedholograms, as well as watermarks andbarcodes. As well as presenting achallenge to counterfeiters, thesemeasures also prove costly to recreate,often cutting into whatever profits thesemanufacturers are making on the blackmarket. Track and trace technology iscommon across a variety of industries,from food to pharmaceuticals. It helpsmanufacturers follow a shipment fromend-to-end, ensuring that what leavesthe production line is exactly what arrivesin a pharmacy, hospital or supplier. In theevent that counterfeit products flood themarket, a company can reassureconsumers that their own products aresafe and secure. But counterfeiters are cunning, and willexplore new ways of recreating existingmethods, no matter how robust. To thatend, the World Health Organisation andthe US Food and Drug Administrationactively encourage the pharmaceuticalindustry to integrate advanced anti-counterfeiting packaging technology, andto explore new possibilities. In turn, itcreates ever more robust solutions, andcreates value for makers and suppliers ofanti-counterfeit packaging technology. As consumers turn to cheaperalternatives, the risk of takingunregulated medicines that can lead tosevere side effects and even death rises.To tackle the issue, manufacturers andregulators are incorporating increasinglyinnovative anti-counterfeit measures asstandard for packages. As the market isforecast for impressive growth over thecoming years, it shows the severity ofthe issue, but also how the solution isgoing from strength to strength.© Shutterstock / Tatiana Popova17-19_Layout 1 09/06/2017 13:31 Page 3Next >