Medicines In DevelopMent Biologics - PhRMA
2013 REPORTMedicines in DevelopmentBiologicspresented by america’s biopharmaceutical research companiesOverviewBiologics Research Promises toBolster the Future of MedicineBiologics In DevelopmentBy Product Category andDevelopment PhaseAmerica’s biopharmaceutical researchcompanies are using biological processes to develop 907 medicines and vaccines targeting more than 100 diseases.Many biologics are made from a varietyof natural sources—human, animal ormicroorganisms. Like small-moleculedrugs, some biologics are intended totreat diseases and medical conditions.Other biologics are used to prevent ordiagnose disease. Examples of biologicalproducts include but are not limited to:338ApplicationSubmittedPhase IIIPhase IIPhase I250 monoclonal antibodies vaccines, including therapeuticvaccines blood and blood products for transfusion and/or manufacturing into otherproducts gene therapies cell therapiesThe medicines discussed in this reportare either in human clinical trials orunder review by the U.S. Food and DrugAdministration reclonalantiborapyrathenomohell tnegeceantisense30These medicines often represent cutting-edge research in which the latestscientific discoveries are translatedinto novel therapies that provide newtreatment options for patients. Increasedunderstanding of the molecular andgenetic bases of disease has opened upthe development of a range of targetedtreatments. For instance, monoclonalantibodies (mAbs) are proteins that helpthe immune system identify and bindto foreign substances. Thirty years afterinitial development, these therapieshelp treat some of the most costly andchallenging diseases.Antisense drugs interfere with the communication process that tells a cell to producean unwanted protein. Vaccines, particularly,therapeutic cancer vaccines, are anotherexample of how the immune system isbeing harnessed to fight disease.The biologics now in development makeuse of a range of new technologies toharness scientific progress. For example,among the medicines in the pipeline are: A genetically-modified virus-basedvaccine to treat melanoma. A monoclonal antibody for the treatment of asthma. A n antisense therapy for the treatmentof leukemia. A recombinant fusion protein to treattype 2 diabetes.For more information on these productsand others, please see page 4 and ouraccompanying backgrounder.The 907 biologics in developmentpromise to push the frontiers of scienceand bring new treatments to patients forour most challenging diseases. See ourreport for a full list of the medicines andvaccines in development.This overview discusses the sciencebehind biologics, potential medicines ofthe future, the need for continued investment in research and development, andthe policies and regulations that helpmake such innovation possible.
The Human GenomeAdvancing Biomedical ScienceInside every human body are about 25,000 genes—eachresponsible for a specific protein. A person’s genes tell theirbody to produce all the enzymes, hormones, antibodies andother proteins needed to make the body function. If one ofthe genes is missing or defective, the body will not have theproteins it needs to function properly and may have proteinsthat actually cause disease. The modern tools of biotechnology—coupled with computer technology’s ability to analyzemassive amounts of data quickly—help biopharmaceuticalscientists determine which genes or proteins are defectiveand are being used to develop new treatments across a rangeof therapeutic areas.Over the past decade, a wave of scientific advances and newtechnologies have dramatically changed how medicines arediscovered. Greater knowledge of how diseases work at thegenetic and molecular level has allowed researchers to pursuenew targets for therapy and better predict how certain biopharmaceuticals will affect specific subpopulations of patients.Manufacturing ComplexitiesMost biologics are very complex molecules and cannot befully characterized by existing science. For this reason, theyoften are characterized by their manufacturing processes.Given the complexity of many biologics, the manufacturingprocesses are likewise complex and very sensitive. Slightchanges in temperature or other factors can impact the finalproduct and affect how it works in patients. Changes in themanufacturing process or facility may require clinical studiesto demonstrate safety, purity and potency. Bioinformatics—Bioinformatics use systems and mathematical models to advance the scientific understanding ofliving systems. At its simplest level, bioinformatics involvesthe creation and maintenance of biological databases,including DNA sequences. Bioinformatics also includescalculation tools. These tools can decipher the molecularpathways of disease, find patterns in the way genes respond to drugs, interpret the three-dimensional structureof important proteins, and enable the computer-aideddesign of new drugs. B iomarkers—Every disease leaves a signature of molecular“biomarkers” in our body—genes that turn on and off orproteins released into the bloodstream. Biomarkers measured in blood and other samples can tell us the state ofour health and how we might respond to treatment. Theyare powerful tools that can detect certain diseases at theirearliest stages before symptoms appear, when they aremost treatable. The identification of biomarkers is the firststep in developing a personalized medicine. M olecular Targeting—The idea behind molecular targetingis to design drugs that specifically attack the molecularpathways that cause disease, without disrupting the normal functions in our cells and tissues.biologic moleculelaspirin moleculeMonoclonal Antibodies:Targeted Cancer TherapyAn approved monoclonal antibody (mAb) for thetreatment of cancer targets the epidermal growthfactor (EGFR) that is linked to the growth anddevelopment of many types of cancer. Originallythe mAb was approved for the treatment of EGFRexpressing metastatic colorectal cancer. Additionalstudies have found that the presence or absence ofa certain gene mutation could predict the patients’response to treatment. Patients without the genemutation—about 65% of patients—are most likely tobenefit from treatment.2 N anotechnology—You can’t see it, but soon it will be everywhere. Nanotechnology is the science of building microscopic devices at the molecular and atomic levels. In medicine,nanotechnology may also be used to help diagnose andtreat diseases. For example, tiny gold-coated “nanoshells”could act like smart bombs, zeroing in on a tumor, enteringcancer cells, and lying in wait until an infrared beam or radio wave signals the particles to release an intense, deadlydose of heat energy that destroys the cancer cells. P ersonalized Medicine—The sequencing of the humangenome produced a “map” of the human genes in DNA.This new genetic knowledge opens up the possibility ofdeveloping “targeted” therapies for people with specificgene sequences, and it can help physicians choose thebest treatments based on individual genetic, lifestyleand environmental factors. Additionally, researchers aredeveloping genetic tests that can tell if we are susceptibleto certain diseases.OVERVIEW Medicines in Development BIOLOGICS
Key Biologic Medicines Approved in theLast Decade The first genetically engineered antibody approvedto prevent the formation of new blood vessels thatprovide tumors with oxygen and nutrients—a process called angiogenesis. The medicine was approvedfor the treatment of metastatic colorectal cancer. Usingangiogenesis as an approach to fight cancer was firstdiscussed more than 30 years ago. In 1989, biopharmaceutical company scientists discovered a key growthfactor influencing the process that led to the discoveryand development of the medicine. A first-in-class human monoclonal antibody thattargets the cytokines interleukin-12 (IL-12) and interleukin-23 (IL-23). IL-12 and IL-23 are naturally occurringproteins that are believed to play a role in the development of psoriasis. The medicine is delivered by injectionfour times a year after two initial doses within four weeks. A recombinant vaccine for the prevention of humanpapillomavirus (HPV) which can lead to cervical andother cancers. The vaccine was approved for the prevention of cervical diseases caused by human papillomavirus(HPV) types 16 and 18 for use in females ages 10 to 25.In clinical trials, the vaccine was shown to be 93 percenteffective in preventing cervical pre-cancers associatedwith HPV 16 and 18 in women with no prior exposure toHPV of the same types. The first in a new therapeutic class called autologouscellular immunotherapy. Approved for the treatmentof metastatic, castrate-resistant (hormone-refractory)prostate cancer, the medicine was designed to inducean immune response against prostatic acid phosphatase(PAP), an antigen expressed in most prostate cancers.Each dose is manufactured using the patient’s own immune cells from the blood. To enhance their therapeuticresponse against the cancer, the immune cells are thenexposed to the PAP antigen and linked to an immunestimulating substance. When this process is complete,the patient’s cells are returned intravenously to the patient to treat the cancer. The first new medicine approved to treat adults withactive lupus in over 50 years and the first in a new classof biologic therapies called BLyS-specific inhibitors.Researchers identified a naturally occurring protein inthe human body called B-lymphocyte stimulator (BLyS).Clinical studies have shown that there is a connectionbetween higher levels of BLyS and lupus disease activityin some people. This new monoclonal antibody delivered2013 ReportRNA Interference (RNAi)RNA interference therapeutics are an exciting newfrontier for the development of novel therapies forpatients, especially patients with genetic disorders.There are several RNAi therapies in clinical trialswhich have demonstrated potential in treatingcertain neuromuscular disorders, such as DuchenneMuscular Dystrophy (DMD). DMD is a genetic disorderimpacting 1 in 3,500 newborn boys and is the mostsevere form of muscular dystrophy in childhood. OneRNAi targeted therapeutic in development seeks torestore the function of dystrophin. Early clinical trialsof the drug have demonstrated significantly improveddystrophin expression as well as improvement inDMD patients’ ability to walk.Over the past decade, biologicshave accounted for one-third of newmedicine approvals.through an intravenous (IV) infusion, binds to BLyS andprevents it from stimulating B cells. Adding this therapyto other lupus treatments may help reduce the abnormalimmune system activity that contributes to disease activity in lupus. The first in a new class of antibody-drug conjugates(ADC) which utilizes a monoclonal antibody to directa therapeutic drug to target the cancer cells. It was approved to treat Hodgkin lymphoma and systemic anaplastic large cell lymphoma (ALCL), a rare type of lymphomathat represents only 3 percent of all non-Hodgkin lymphomas. ADCs combine a monoclonal antibody and a therapeutic drug, where the antibody directs the therapeutic totarget the cancerous cells. It is also the first FDA-approveddrug for Hodgkin lymphoma in more than 30 years andthe first to specifically treat ALCL. It is composed of ananti-CD30 monoclonal antibody and a microtubuledisrupting agent and releases its therapeutic drug onceinside the CD30-expressing tumor cells.3
Medicines in the FutureBuilding on the impressive progress to date, the 907 medicines and vaccines listed in the PhRMA report, BiologicMedicines in Development, represent the next excitingfrontier of biopharmaceutical research.The report finds that the greatest amount of research is inmonoclonal antibodies (mAbs), with 338 separate mAbs indevelopment, and vaccines, with 250 vaccines in clinicaltrials or under review at FDA.Analysis: Cancer and Infectious Diseasesand TechnologiesThe report on biologics finds that a great deal ofresearch is focused in two diseases areas—cancerand infectious diseases. Within these categories,biopharmaceutical researchers are investigatingseveral different techniques and technologies to treatand prevent disease.CancerVaccines - 89Other - 24Antisense - 8Celltherapy - 15Recombinantproteins - 15Genetherapy - 17Monoclonalantibodies - 170Infectious DiseasesAntisense - 5Celltherapy - 1Genetherapy - 3Monoclonalantibodies - 22Vaccines - 1344Recombinantproteins – 2MAbs were first explored as a therapeutic option as a result ofscientific breakthroughs that occurred in the mid-1970s andearly-1980s. By 2013, a total of 33 mAbs were approved in theUnited States. Because mAbs allow targeting of unhealthycells without harm to healthy cells, they have been particularly important in fighting cancer, and more recently, showgreat promise for autoimmune diseases, such as rheumatoidarthritis. Vaccines have historically been used as a preventative tool in infectious diseases, such as pneumonia, HIV andsmallpox. But today, vaccines are also being used as therapiesfor cancer and other diseases.Below are examples of some of the exciting new biologicmedicines in the pipeline:Monoclonal Antibodies (mAb) A mAb designed to block the IL-13 cytokine, a proteinmessenger between cells that triggers inflammation.Blockage of IL-13 may reduce the risk of asthma andother respiratory diseases. A mAb that targets B-cells that cause the immune systemto turn against itself and produce antibodies against thebody’s own cells and tissue. A mAb for the treatment of psoriasis is an engineeredhuman antibody to interleukin-17 (IL-17), a key cytokineinvolved in inducing and mediating inflammation associated with psoriasis. A mAb directed against interleukin-6 (IL-6) alpha, asignaling protein involved in the regulation of immuneand inflammatory responses associated with rheumatoidarthritis. The mAb interrupts the inflammatory signalingcascade of IL-6 by blocking its binding to a certain receptor necessary for inflammatory cascade. A mAb for potential use in the regeneration of corticospinal tract fibers resulting from an acute spinal injury.The antibody neutralizes a protein that inhibits growth ofspinal fibers.Antisense A third-generation antisense medicine in developmentfor the treatment of lymphoma inhibits production of aspecific protein which regulates many key genes important in cancer growth—angiogenesis, cell metabolism,cell proliferation, cell death and cell invasion. An overexpression of the protein in tumors results in resistance totreatment. By reducing the amount of the protein in cancer cells, the antisense medicine may be able to enhancethe effectiveness of current anticancer treatment.OVERVIEW Medicines in Development BIOLOGICS
Therapeutic VaccinesRNAi—RNA Interference A virus-based therapeutic vaccine in development for thetreatment of melanoma is genetically-modified to replicate selectively in tumor cells and express a gene for animmune-stimulating protein. It is injected directly into thetumor where it replicates and spreads within the tumor,causing the death of cancer cells and stimulating theimmune system to destroy cancer cells. An immunotherapeutic designed to train the immunesystem to recognize and eliminate cancer cells in a highlyspecific way. The medicine is a combination of tumor antigens, delivered as recombinant proteins, and a proprietaryadjuvant (an agent that modifies another substance in itsaction) to stimulate the immune response to cancer cells.It is intended to only affect cancer tissue and not harmnormal tissue. An RNAi-targeted therapeutic in development seeks torestore the function of dystrophin. Early clinical trials ofthe medicine have demonstrated significantly improveddystrophin expression as well as improvement in DMDpatients’ ability to walk.Stem Cell Therapy Researchers are exploring transplantation of a patient’sown bone marrow cells into damaged heart tissue toregenerate heart tissue. It is believed that a patient’s immune system will not attack the newly transplanted cellsbecause they are native to the patient.Gene Therapy A gene therapy employs an adeno-associated virus (AAV)as a vector to deliver to the gene neurturin, which hasbeen found to restore cells damaged in Parkinson’s patients and protect them from further degeneration.Biologic Medicines in Development—by Therapeutic CategorySome medicines are listed in more than one categoryAutoimmune Disorders71Blood Disorders43Cancer/Related Conditions338Cardiovascular Disease58Diabetes/Related Conditions28Digestive Disorders26Eye Conditions25Genetic Disorders30Infectious Diseases176Musculoskeletal Disorders34Neurologic Disorders39Respiratory Disorders38Skin Diseases30Transplantation13Other58Biologic Medicines in Development—by Product CategoryAntisense30Cell Therapy69Gene TherapyGrowth FactorsInterferons46710Monoclonal Antibodies (mAb)338Recombinant Hormones/ProteinsRNA Interference9315VaccinesOther2013 Report250495
Encouraging ContinuedBiopharmaceutical InnovationThe development of new biologics is a long, complex andcostly endeavor. It takes about 10–15 years, on average, tobring a medicine through the discovery and clinical trialphases to patients, and the average R&D investment for eachnew medicine is 1.2 billion, including the cost of failures.Another report on medicines in the pipeline found that morethan 5,000 potential new medicines—which may becomeavailable to U.S. patients—are in the pipeline globally—inlarge part funded by the more than 500 billion investedin research and development (R&D) since 2000 by PhRMAmember companies. These promising candidates build onthe more than 300 medicines that have been approved bythe FDA in the last decade.In order to realize the full potential of biologics, it is essentialthat the United States maintain strong policy and regulatoryenvironments that help foster the discovery and development processes.Human Clinical TrialsPhase I—Researchers test the biologic/drug in a smallgroup of people, usually between 20 and 80 healthyadult volunteers, to evaluate its initial safety andtolerability profile, determine a safe dosage range, andidentify potential side effects.Phase II—The biologic/drug is given to volunteerpatients, usually between 100 and 300, to see if itis effective, identify an optimal dose, and to furtherevaluate its short-term safety.Phase III—The biologic/drug is given to a larger, morediverse patient population, often involving between1,000 and 3,000 patients (but sometime many morethousands), to generate statistically significantevidence to confirm its safety and effectiveness. Theyare the longest studies, and usually take place inmultiple sites around the world.The Future of Research Should BeProtected by Adequate Incentives forInnovation; 12-Years of Data Protection isCritical for PatientsA biosimilar is similar to—but not the same as—aninnovator biologic. A pathway for the approval ofbiosimilars in the United States was included in thePatient Protection and Affordable Care Act of 2010.The pathway, which received broad bipartisansupport in both chambers of Congress, struck anappropriate balance between promoting increasedcompetition and providing adequate incentives tosupport continued innovation of new treatments andcures through a 12-year period of data protection.This is critical to spurring the investment in researchand development needed to seize the extraordinaryopportunities for medical advances against our mostcostly and challenging diseases and the resultingjobs supported across the U.S. economy.The Promise of PDUFA VAn efficient, consistent and predictable science-basedregulatory system is critical to providing innovative newmedicines to patients. The recently reauthorized Prescription Drug User Fee Act (PDUFA V) will help foster timelypatient access to new medicines, enhance the FDA’s regulatory science capacity and encourage future innovationwhile strengthening the Agency’s high safety standards. Itprovides for increased scientific communication betweenFDA and drug sponsors during the regulatory review of newmedicines which has the potential to increase first-cycleapproval rates and bring new medicines to patients faster. PDUFA V will also advance regulatory science throughresources to validate the use of new scientific tools (suchas pharmacogenomics and biomarkers) and meta-analysesthat will help decrease drug development time.U.S. pharmaceutical companies accountfor 80% of the world’s R&D in health carebiotechnology.6OVERVIEW Medicines in Development BIOLOGICS
The Biomedical Research EcosystemThe collaborative ecosystem that exists in the United Statesbetween the government, academia, and biopharmaceuticalcompanies is among our greatest strengths in moving medicaladvances forward and has helped position the United Statesas the worldwide leader in biopharmaceutical innovation.Biopharmaceutical companies today are engaging in a widerange of partnerships in new and promising ways. Suchpartnerships include unrestricted research support, academicdrug discovery centers and pre-competitive research centers.As scientists have probed deeper into the causes and signs ofdisease the amount of information that is available has exploded, but making sense of all the data is a colossal undertakingthat no single individual or institution can handle alone.As a result, biopharmaceutical research companies areworking with other companies, academic medical centers,the government, and in some cases non-profit organizations to share, organize and make sense of huge volumes ofinformation. In some instances, they are working togetherin innovative ways to share information to advance progressagainst disease.An example of this kind of collaboration is the Alzheimer’sDisease Neuroimaging Initiative, which includes federalagencies, non-profit organizations, and biopharmaceutical industry members. The goal of the Initiative is to trackAlzheimer’s disease progression, establish quality standardsand validate biomarkers to be used in clinical trials. Datacollected are made available at no cost to researchers whendesigning clinical trials and research projects.Corporate Venture Capital Investmentsare Helping Advance Biotechnology R&DAnother evolving aspect of the biomedical research ecosystem relates to the investment necessary to support emergingbiopharmaceutical companies. Historically, venture capitaland other forms of private capital have been key sourcesof financing for start-up and emerging biopharmaceuticalcompanies.But, as traditional venture capital has recently declined due toseveral factors including regulatory challenges and concernsabout coverage and payment of new medical innovations,the corporate venture arms of established biopharmaceuticalcompanies have become an increasingly important source ofcapital to help fill this gap. Between 2010 and 2011, biopharmaceutical companies invested nearly 700 million in venturecapital in biotechnology start-ups, according to a 2011 MoneyTree report. And corporate venture activity is on the rise.According to a recent report by the Boston Consulting Group,63% of the 30 largest biopharmaceutical companies currentlyparticipate in corporate venture capital investments—upfrom 50% in 2007.SummaryThe 907 biologic medicines and vaccines currently in development offer great hope for patients, building upon thesignificant progress in the last few decades across a widearray of diseases. America’s biopharmaceutical researchecosystem is uniquely positioned to deliver on the greatpromise of science if supported by policy and regulatoryenvironments that encourage continued innovation.In the human bodythere are12 trillion cells,200,000 proteins and25,000 genes2013 Report7
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promise to push the frontiers of science and bring new treatments to patients for our most challenging diseases. See our report for a full list of the medicines and vaccines in development. This overview discusses the science behind biologics, potential medicines of the future, the need for continued invest-ment in research and development, and
TABLE 2: R&D as a Percentage of Sales, PhRMA Member Companies: 1981–2019 *Revised in 2007 to reflect updated data. Source: Pharmaceutical Research and Manufacturers of America, PhRMA Annual Membership Survey, 2020. Function Dollars Share Pre-Human/Pre-Clinical 13,034.3 15.7% Phase I 7,26
The Pharmaceutical Research and Manufacturers of America (PhRMA) appreciates the opportunity to comment on the Department of Health & Human Services (HHS) request for information (RFI), HHS Blueprint to Lower Drug Prices and Reduce Out-of-Pocket Costs. PhRMA represents the country's leading innovative biopharmaceutical research companies,
The Pharmaceutical Research and Manufacturers of America (PhRMA) represents the country’s leading innovative pharmaceutical research and biotechnology companies, which are devoted to developing medicines that allow patie
NEW MEDICINES, BETTER MEDICINES, BETTER USE OF MEDICINES 3 FOREWORD FOREWORD The Society leads and supports the development of the pharmacy profession including the advancement of science, practice, education and knowledge in pharmacy, as well as promoting public understanding of pharmacy
Before we get into the detail there are some commonalities of all stop smoking medicines that you need to know. Stop smoking medicines increase quit rates All stop smoking medicines increase the chances of stopping smoking for good. Smokers should be encouraged to use one of the licensed stop smoking medicines to aid them in stopping smoking.
drugs in terms of Medicare payment account for 60 percent of the total while the top 10 account for 46 percent of total payments in 2017. Spending for biologics has grown much more rapidly than spending for non-biologics over the past ten years. From 2006 to 2017, spending for biologics accounted for nearly all (92 percent) of Medicare Part .
Source: Adis R&D Insight Database1. Industry Efforts for Patients: Bringing New Treatments and Cures to the Market PhRMA members continue to deliver new and innovative products to Japanese patients 25% of all product approvals in 2017 and 2018 were developed by PhRMA Japan’s 12 members of which 41%
Integrity inspection, American Petroleum Institute (API), Steel Tank Institute (STI), Magnetic Flux Leakage (MFL), Ultrasonic Testing (UT), National Fire Protection Association (NFPA). WHAT IS AN INTEGRITY INSPECTION An integrity inspection of a container(s) is a system designed to be sure that a container would not fail under normal operating conditions. In this application, it generally .
