Biotech
BioTech in 2023 – Alzheimer’s, Sickle-Cell, and Obesity
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The biotechnology industry has seen significant growth in recent years, with research in the sector providing valuable insight to enhance medical treatments to combat diseases, improve the quality of life, and extend the human lifespan.
Biotech is the branch of applied science that produces healthcare-related products by making use of living organisms. It combines several disciplines, including science, biology, physics, chemistry, mathematics, and technology.
Companies like Eli Lilly, Merck, Pfizer, Amgen, Gilead Sciences, Biogen, Modena, Regeneron Pharmaceuticals, Johnson & Johnson, Roche, Idec, Celgene, and AbbVie have been spending millions of dollars to research and develop solutions in the field of healthcare, medicine, genomics, food production, biofuels, and environmental safety.
With a size of $860 billion, the industry is set to almost double in market value by the end of this decade. This year, continuous research and development have already resulted in many exciting breakthroughs with prominent discoveries and the most progressive advancements made to combat Alzheimer's, sickle cell, and Obesity. So, let's take a look at them!
The New Treatments for Alzheimer's Disease
Alzheimer's disease (AD) is increasing at a fast pace, with an estimated 6.2 million individuals with AD dementia in the US and an estimated 55 million individuals with AD dementia globally.
A progressive disorder, Alzheimer's disease is the most common type of dementia, which starts with mild memory loss. The disease damages and destroys brain nerve cells that control thought, memory, and language. Over time, it leads to a gradual loss of the ability to remember, reason, use language, and respond to the environment. There may even be a range of behavioral changes due to Alzheimer's disease.
However, 2023 has marked a big milestone in AD treatment. Scientists and researchers continue to unravel the complexities of Alzheimer's to not only better understand and treat the disease but also prevent it completely.
Earlier this year, the US Food and Drug Administration (FDA) gave accelerated approval to the groundbreaking treatment called LEQEMBI (lecanemab-irmb). Developed by Biogen and Eisai, the treatment showed great efficacy in slowing down the progression of the disease as well as moderately reducing cognitive decline in early-stage AD patients. This was actually the first treatment proven to affect the course of Alzheimer's disease.
The drug is delivered by an intravenous infusion (directly into a person's vein) every two weeks. The way this drug works is that it removes a sticky protein called amyloid from the brain that is believed to advance Alzheimer's disease.
“It's very exciting because this is the first treatment in our history that shows an unequivocal slowing of decline in Alzheimer's disease.”
– Dr. Christopher van Dyck, director of Yale's Alzheimer's Disease Research Unit, who led the study and is also a paid consultant for the pharmaceutical company Eisai
The trial for the treatment involved 1,795 participants with early-stage, symptomatic Alzheimer's. Published in the New England Journal of Medicine, the Phase III clinical trial results of lecanemab revealed that after a year-and-a-half-long treatment, the drug slowed clinical decline by 27% compared with those who received a placebo. The treatment selectively targets forms of amyloid protein, believed to be “the most toxic to brain cells,” and those who received it showed a significant reduction in the protein in imaging tests.
Study participants also experienced a 37% slowing of decline in a measure of daily living and a 26% slowing of decline in a key secondary measure of cognitive function compared to the placebo group. Concurrently, Lecanemab is being tested in the global AHEAD study, targeting individuals who, although cognitively normal, are at high risk of symptoms due to elevated levels of brain amyloid.
According to Dr. van Dyck, this is just the beginning, with data suggesting:
“The longer the treatment period, the better the effect. We may see a larger benefit if we intervene before significant brain damage has occurred.”
When it comes to side effects, typically flushing, chills, fever, rash, and body aches are seen, with the majority of them being mild to moderate and most occurring right after the first dose. Additionally, there's the potential side effect of imaging abnormalities related to amyloid, which may include brain bleeding, edema, or fluid formation in the brain.
The treatment will be sold under the brand name Leqembi™, with Eisai setting its price at $26,500 per year. However, the price may change given that the federal health insurance program Medicare has said it will cover 80% of the cost without requiring participation in a randomized clinical trial. The Centers for Medicare & Medicaid Services (CMS) confirmed this in the second half of the year.
In July, the FDA also granted full traditional approval to the drug for the first time in two decades. However, there is a “black box” warning, the agency's strongest caution, about brain swelling and bleeding on the medication due to safety concerns.
Besides Leqembi, this year has also brought advancements in Alzheimer's vaccines. The American company Vaxxinity reported successful phase 2 trials of UB-311, targeting toxic amyloid beta forms in the brain, which not only triggered an immune response but also demonstrated safety. Representing a novel approach in Alzheimer's treatment, this synthetic, peptide-based active immunotherapy could pave the way for more enduring and cost-effective alternatives to current treatments by inducing a target-specific antibody response.
These biotech breakthroughs have certainly opened new doors in Alzheimer's research, providing a foundation for future innovations and having more targeted and effective treatments.
New Sickle Cell Disease Gene Therapies are Here
A rare, painful, inherited blood disorder, sickle cell disease (SCD) affects more than 100,000 people in the U.S. and about 20 million people worldwide. This is a lifelong and life-threatening disease that could even lead to early death.
In this condition, the problem is a mutation in the protein found in our red blood cells that carries oxygen, i.e., hemoglobin. Under this mutilation, red blood cells, which are normally disc-shaped, turn into the shape of a “sickle', which tends to stick together. These mutated cells restrict the flow in blood vessels and limit oxygen delivery to your entire body's tissues, leading to severe pain, stroke, infections, and organ failure.
Currently, a bone marrow transplant is the only cure for this life-threatening disease, but that involves the difficult process of finding a matching donor as well as the risk of rejection by the immune system. As a result, gene therapy has emerged here as a possible cure for this potentially fatal disease.
In 2023, gene and cell therapies for treating SCD moved closer to getting into the market than ever. In a landmark decision, the US Department of Health and Human Services approved the first cell-based gene therapies to treat SCD in patients aged 12 years and older. These treatments include Casgevy by Boston-based CRISPR Therapeutics and Vertex Pharmaceuticals and Lyfgenia by drugmaker Bluebird Bio Inc.
Out of the two, Casgevy is the first FDA-approved treatment developed using CRISPR-Cas9 genome editing technology, which, according to Vertex, was chosen due to its ability to deliver permanent and precise edits at a specific location but “without evidence of off-target effects.”
In CRISPR-Cas9, patients' DNA is cut in targeted areas, then accurately edited to add, remove, or alter the DNA, and then modified cells are transplanted back into the patient. Once inside, they link and grow within the bone marrow and increase fetal hemoglobin (HbF) production to prevent the sickling of red blood cells. Vertex said:
“We are very pleased with the strength of our data for exa-cel – efficacy, safety and durability of response – and we believe the data presented at EHA established a differentiated profile in SCD.”
Lyfgenia didn't make use of CRISPR. Instead, it went the traditional route of gene therapy treatment by utilizing a lentiviral vector, a family of viruses, to modify genes. Here, the blood stem cells of SDC patients are genetically modified to produce a special hemoglobin HbAT87Q that functions much like any normal adult hemoglobin but is gene-therapy derived and delivered to the patient.
In the case of the cell-based gene therapy Casgevy, a total of 44 patients were in the trial. Of these,31 of them had sufficient follow-up time to be evaluated, which revealed 29 patients got rid of severe VOC episodes for at least a year, while all of them had no graft rejection or failure. Similarly, in the trial for Lyfgenia, 22 out of the 32 patients achieved complete resolution of VOEs.
When it comes to side effects, mouth sores, nausea, vomiting, headache, fever, and low levels of platelets and white blood cells were the most common ones. In Casgevy's case, there was also musculoskeletal pain and abdominal pain, while in Lyfgenia, hematologic malignancy or blood cancer was also reported, which got it a boxed warning from the FDA after two trial patients died from a form of leukemia.
But this is not all. These novel therapies also show promise for treating other illnesses beyond their current applications. For instance, CRISPR-based treatments are not limited to SCD; they have the potential to address inherited blood disorders like beta-thalassemia. Moreover, they could be effective against familial hypercholesterolemia, an inherited form of high cholesterol, and even amyloidosis, a rare liver condition. The successful application of CRISPR in these areas underlines the broad potential for gene editing to revolutionize medicine by providing solutions for many previously untreatable diseases and significantly improving public health.
While it's a big movement, this is just the beginning, and much work needs to be done in order to make the therapy widely accessible, with the biggest barrier being the cost. These new therapies will cost north of a million dollars, which means not only people in other countries but most Americans will also be priced out. Hence, there is clearly a long way to go for these gene-editing treatments to become more accessible.
Tackling the Problem of Obesity Head-on
2023 has also been a transforming year in the biotech industry to tackle obesity with new weight loss and diabetes drugs like Ozempic and Wegovy from Novo Nordisk, taking the world by storm. These new drugs showed immense effectiveness at causing weight loss, hence their popularity.
Belonging to the GLP-1 analogs class of medications, these new drugs work by activating a critical GLP-1 hormone produced by the gut in response to eating and help in losing weight by reducing appetite, slowing down stomach emptying, and boosting insulin release.
In Ozempic and Wegovy, the active ingredient is semaglutide, while the active ingredient in Eli Lilly's diabetes medication, Mounjaro, is tirzepatide, which also induces weight loss.
As innovative approaches and new treatments make their way into this area, gene therapy is also making its entrance, which can provide long-term solutions for weight management by targeting specific genes responsible for obesity.
With obesity affecting nearly 42% of US adults, which increases the risk of diabetes, hypertension, cancer, and heart disease, research and investment to address this is increasing substantially. A new study, supported by grants from the NIH, Novo Nordisk, the National Science Foundation, the Department of Mechanical Engineering at MIT, and a Schmidt Science Fellowship, notes the need for alternative methods due to difficulty in modifying behaviors and limitations of pharmacologic therapies.
The research titled “A vibrating ingestible bioelectronic stimulator modulates gastric stretch receptors for illusory satiety,” which was published in Science Advances, noted that effective therapies to manage this disease require high patient adherence or invasive surgical interventions. Hence, a device called a vibrating, ingestible bioelectronic stimulator or VIBE was suggested.
With its new device, MIT engineers are taking advantage of the normal functions of our body — when we eat a large meal, our stomach becomes distended, and mechanoreceptors sense it and then send signals to the brain via the vagus nerve, resulting in the production of hormones and insulin, all of which help people digest food, feel full, and stop eating while levels of hunger-promoting hormone called ghrelin go down.
In the case of VIBE, an illusion of expansion is created to adjust eating habits. Instead of drinking a glass of water before eating, here you take a pill.
The device is designed to be orally ingested so as to sustain contact with the gastric lining, activate when submersed in gastric fluid, vibrate with amplitudes sufficient to stimulate gastric intraganglionic laminar endings (IGLEs) for a set time period and pass safely through the GI tract.
This new device, in the form of a pill, is powered by a small silver oxide battery. When swallowed, it travels through the gut, making contact with gastric fluid. This interaction causes the gut to vibrate for about 30 minutes, stimulating the vagal nerve — akin to the effects of gastric bypass surgery — and, consequently, creates the sensation of being full.
The new invention is likened to Ozempic and Wegovy in that it helps people manage their calorie intake and prevent weight gain.
According to former MIT graduate student Shriya Srinivasan, Ph.D., who is an assistant professor of bioengineering at Harvard University, people who want to not just lose weight but also control their appetite can take this pill before each meal. Srinivasan, who is the lead author of the new study, added:
“This could be really interesting in that it would provide an option that could minimize the side effects that we see with the other pharmacological treatments out there.”
To study the performance of VIBES, the researchers used Yorkshire pigs (due to their gastric anatomy being similar to that of humans) weighing 50- 80 kg and between the ages of 4 and 6 months. The pill was endoscopically deployed into their gastric cavity. Besides stimulating the release of hormones signaling satiety, when the animals were given the pill 20 minutes before eating, they had a significant reduction in their intake of food. As per the study, it “consistently led to diminished food intake” by about 40% and lessened the rate of weight gain.
The study, according to its senior author, Giovanni Traverso, a gastroenterologist at the Brigham and Women's Hospital:
“Demonstrates the effectiveness of a low-cost, non-invasive intervention to reduce food intake and calorie consumption.”
But while the device functions effectively to induce satiety and, as Traverso believes, “has the potential to revolutionize therapeutic options for patients with obesity,” there's still a need for more studies to “explore the physiological effects of the device before it's available for patients.”
Overall, an increased understanding of obesity has led its drug market to expand rapidly. Moreover, as more people recognize it as a serious medical condition, we are seeing the demand for these drugs rising exponentially, as well as for more effective treatments.
Click here for the list of top companies in the obesity treatment space.
Concluding Thought
As we saw, biotechnology has made a lot of breakthroughs in treating Alzheimer's, sickle cell, and Obesity. Besides these, we have seen many developments in precision genome editing, synthetic biology, oncology, organs-on-chips, next-gen sequencing, and artificial intelligence.
As the industry continues to tackle some of the most challenging health issues, we will see even more advancements and trends next year that will create big waves for years or decades to come and enhance our lives.
