As thought leaders working with companies at the forefront of science and technology, we spend much of our time looking to the future. It is often at the dinner table with friends and family that we are asked what have been the most important breakthroughs of all time. A good question, and not an easy one to answer. However in this simple infographic we describe 15 drug innovations throughout ‘recent’ history, from the first successful vaccine developed in the late 18th century to today’s personalized gene therapy treatments.
In this blog post, we expand on our ‘15 breakthrough drug innovations’ infographic to flesh out the details of some of the medicines that have helped to transform healthcare.
English doctor Edward Jenner conducted a famous experiment that involved inserting fluid taken from a cowpox pustule into an incision on the arm of an eight-year-old boy. He proved that this inoculation provided immunity to smallpox – one of the world’s biggest killers at the time. This milestone discovery was the first vaccine to be developed against a contagious disease. Smallpox was eradicated in the late 1970s, with the last natural case occurring in 1977. The elimination of this disease by a global vaccination programme is considered to be one of the greatest ever achievements in international public health.
While working for pharmaceutical firm Bayer, German chemist Felix Hoffmann acetylated salicylic acid with acetic anhydride – producing acetylsalicylic acid in a stable and chemically pure form. The substance, which had pain-relieving, anti-inflammatory and fever-lowering properties, was launched for the first time in 1899 under the trade name Aspirin. It is the most widely used mild analgesic and can also help to prevent heart attacks and strokes. Recent research even suggests that regular use can lower the risk of certain cancers. According to a study published in the journal PLOS ONE, in the US alone routine aspirin use in patients aged 51 to 79 could prevent 11 cases of heart disease and four cases of cancer for every 1,000 people, and it could raise national life expectancy by around four months.
In 1921, Canadian physician Frederick Banting and medical student Charles Best discovered the hormone insulin in extracts taken from dogs’ pancreases. They injected this hormone into a diabetic dog and found that it lowered the animal’s blood glucose levels to normal. By the end of 1922, insulin had been successfully used to treat a boy suffering from severe diabetes. Since its discovery, insulin has transformed the treatment of diabetes and saved millions of lives.
In the late 1920s, Scottish physician Alexander Fleming discovered the bacteria-killing potential of the mould penicillin. In 1942, the first patient was successfully treated with penicillin and by the end of the Second World War, American pharmaceutical companies were manufacturing 650 billion units of the medicine a month. The discovery of penicillin marked the beginning of the development of antibiotics. Over 100 of these medicines have been developed since and they have revolutionised the treatment of infectious diseases worldwide, significantly increasing life expectancies and transforming medicine as a whole. Prior to penicillin, there were no effective treatments for diseases such as tuberculosis and syphilis, and even small wounds could kill if they became infected. As well as helping to cure patients of a wide range of infections, penicillin allowed surgeons and doctors to carry out more invasive treatments that were previously too risky due to the potential for infection. It is estimated that penicillin has saved approximately 200 million lives.
Until the 1950s, there were no effective drug therapies for mental illnesses. This changed in 1952 when chlorpromazine was synthesised in the laboratories of French pharmaceutical company Rhône-Poulenc. As the first antipsychotic medicine, it was life-changing for schizophrenia patients and proved to be instrumental in the development of neuropsychopharmacology. Its commercial success spurred the development of other psychotropic drugs. By introducing pharmacological treatments for psychiatric conditions, neuropsychopharmacology has helped to transform the lives of patients suffering from a wide range of mental illnesses.
Capoten, which is a brand name for the medicine captopril, is a treatment for high blood pressure. Captopril was first synthesised by Miguel Ondetti and David Cushman in 1974 and it entered the market in 1981 as the first angiotensin-converting enzyme (ACE) inhibitor. Its effects mimic those of the venom of the poisonous snake Bothrops jararaca. Although it has been superseded by other ACE inhibitors that are easier for patients to use, its creation is widely acknowledged to be one of the great advances in cardiovascular medicine. As well as being used to treat high blood pressure, ACE inhibitors are commonly prescribed to patients who have suffered heart attacks or heart failure. They are therefore a hugely important treatment for many millions of people around the world.
The antidepressant fluoxetine hydrochloride, branded Prozac, was approved for the treatment of depression by the US Food and Drug Administration (FDA) in 1987. Developed by researchers Ray Fuller, David Wong and Bryan Molloy at pharmaceutical firm Eli Lilly and Company, it is a selective serotonin-reuptake inhibitor (SSRI). The drug was found to be effective and produced fewer side effects than other treatments. Prozac had the fastest ever acceptance of a psychiatric drug and within five years, 4.5 million Americans had taken it. As well as depression, Prozac can be used to treat bulimia and obsessive compulsive disorder.
The first approved protease inhibitor, saquinavir was developed by Roche and is an antiretroviral treatment used in the therapy and prevention of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). In the year of saquinavir’s release, researchers discovered that HIV was highly susceptible to mutation. This led the FDA to authorise the use of saquinavir in combination with other medicines to mitigate HIV drug resistance. This revolutionised HIV/AIDS treatment and led to multi-drug combination therapy known as highly active antiretroviral therapy. In what is widely considered to be one of the greatest healthcare success stories of recent times, these treatments have turned what was once regarded as a terminal illness into a manageable condition. Today, young people with HIV who use the latest antiretroviral therapies can expect a near-normal life expectancy.
Atorvastatin, which is currently sold under the brand name Lipitor, was developed by the chemist Bruce Roth and launched in 1997. A treatment for high cholesterol, it is nicknamed turbostatin and is a synthetic inhibitor of HMG-CoA reductase, which is the rate-controlling enzyme in the synthesis of cholesterol. Lipitor became the top-selling statin just three years after it was first released, and it was one of the world’s best-selling drugs for a time. Statins, including atorvastatin, are among the most commonly prescribed drugs in the UK. In 2018, more than 71 million statin prescriptions were dispensed in England alone. This was up 46 per cent on 2008. Decades of research supports the use of these medicines to reduce the risk of cardiovascular problems such as strokes and myocardial infarction.
Approved as a drug for human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer in 1998, Herceptin (trastuzumab) is a monoclonal antibody (mAb) treatment. The drug blocks the receptor activity of HER2. Eight years after it was first approved, Herceptin’s use was expanded to include post surgical treatment of HER2-positive breast cancer. One of the great success stories of cancer treatments, it significantly increased survival rates. As well as saving the lives of many women with aggressive breast cancer, it opened the door to new areas of research that have led to multiple other therapies targeting the genetic roots of the disease.
Rapamycin, also known as sirolimus, was approved as an immunosuppressant treatment to prevent organ transplant rejection in 1999. Marketed by Pfizer under the name Rapamune, it lowers the body’s natural immunity to help improve the success of organ transplants. The medicine is also indicated for the treatment of patients with the rare progressive disease lymphangioleiomyomatosis (LAM). In addition, rapamycin is being investigated as a possible cancer and anti-ageing treatment, and last year Orchestra BioMed announced that in partnership with Terumo Corporation, it had secured breakthrough device designation by the FDA for its Virtue sirolimus-eluting balloon, which is used in the treatment of below-the-knee peripheral arterial disease. The device is designed to deliver a sustained-release sirolimus formulation to the artery during a balloon angioplasty procedure.
Injected under the skin, Humira (adalimumab) is a mAb used to treat a range of autoimmune diseases, including rheumatoid arthritis, chronic plaque psoriasis, ankylosing spondylitis (AS) and Crohn’s disease. Humira is also now the only FDA-approved treatment for moderate to severe hidradenitis suppurativa, a painful skin condition that causes abscesses and scarring and affects around one per cent of the population. One of the world’s top-selling medicines, Humira has been referred to as “the Swiss army knife of pharmaceutical drugs”. Although it was not the first mAb to be approved, it was the first fully human antibody to be used. The reason why it can treat so many seemingly diverse conditions – and hence why it has made such an impact on healthcare around the world – is because these medical problems all have one thing in common: inflammation linked to the protein TNF-alpha.
Keytruda (pembrolizumab) was approved by the FDA in 2014 and is used to treat a range of cancers. It is among a group of drugs that initiated the era of immuno-oncology, which refers to harnessing the body’s own immune system to fight cancer. It is a humanised mAb that activates the T-cell-mediated immune response against tumour cells. These therapies can be more targeted than conventional treatments such as radiation and chemotherapy. Keytruda is projected to be the largest oncology drug ever and it can be used to treat a wide range of cancers, including non-small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma and renal cell carcinoma. Highlighting the potential benefits of the drug, research has shown that nearly a fifth of lung cancer patients treated with Keytruda were alive five years later, compared to just five per cent before the development of immuno-oncology-based therapies.
A cell-based gene therapy, Kymriah was the first chimeric antigen receptor T-cell therapy to receive regulatory approval for the treatment of acute lymphoblastic leukaemia – a type of cancer that affects the white blood cells. The patient’s T-cells are collected and sent to a centre where they are genetically modified to include a new gene containing a protein that directs them to kill leukaemia cells. The modified T-cells are then reintroduced into the patient. Clinical trials have demonstrated that Kymriah offers strong efficacy and durable responses in certain groups of blood cancer patients.
Designed to treat patients with a specific type of retinal dystrophy, Luxturna (voretigene neparvovec-rzyl) is the first gene therapy to be approved by the FDA for the treatment of an inherited disease. It is used in patients who have a mutation-associated retinal dystrophy and it works by delivering a normal copy of the affected gene directly into the retinal cells. Luxturna was recommended for NHS funding last year, and around 100 patients may be eligible for the treatment in England alone.
As this timeline shows, new drugs are constantly being developed – and breakthroughs in medical treatments have accelerated over recent years. One area that is currently of particular interest to many of those working in healthcare is personalised medicine (PM). For drug and device manufacturers, PM offers the chance to develop agents that are targeted to patient groups that do not respond to treatments as intended.
Which breakthrough drugs would you include in your list? You can join the conversation using the hashtag #GreatestDrugInnovations
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