New Biologics for Asthma Treatment

Monoclonal antibodies are typically hyper-specialized white blood cells. They are virtually identical to one another. 

This enables hyper-specificity. Some monoclonal antibody cells only bind to one end of one specific antigen molecule. An antigen part of a particle (like dust) triggers an immune system response.  

Asthma is largely a disorder of an over-reactive immune system. Certain cells overreact when processing an antigen. Instead of producing a cough, an asthma patient's immune system severely constricts airways.  

The antibody binds to certain cells in the system. There are multiple ways this can circumvent the extreme reaction.  

Monoclonal antibodies treat overactive immune systems. Yet, they avoid many of the side effects common to small-molecule drug treatments.

This is because cells can act with precision, while chemical reactions are inevitably generalized. Monoclonal antibodies generally have no impact on molecules (or cells) they don't bind with. 

Moreover, monoclonal antibodies live inside the human body for some time. They can prevent or subdue an asthma attack before it reaches critical levels.

In contrast, acute inhalants only stay in the body briefly. Patients must use these immediately during an attack. 

Genetech collaborated with Novartis Pharmaceuticals Corporation to make Xolair®. The drug earned FDA approval in 2020.

Scientists derived this monoclonal antibody from an ovarian cell line. The original line belonged to a Chinese hamster. These cells have the unique tendency to subvert IgE reaction. 

The chief symptom of IgE-mediated asthma is recurring asthma attacks. These attacks are triggered by particles in the patient's environment.  

During an asthma attack, the immune system releases an extreme amount of histamine. This hormone causes swelling. Swelling can cut off the windpipe. 

This airway restriction can be lethal. The World Health Organization (WHO) notes that roughly 461,000 people die of asthma attacks every year. 

Omalizumab prevents the histamine release and subsequent swelling. In patients with IgE-mediated asthma, IgE cells kickstart a dangerous chain reaction.

When triggered, these cells command mast cells and basophils. These cells then release a dangerous amount of hormones. In turn, these hormones cause extreme swelling.

Omalizumab cells bind to receptors in the immune system cells' chain. This disrupts the chain reaction that causes the attack.

It also binds to receptors on the triggering molecule. This prevents the IgE cells from "noticing" the trigger.  

Omalizumab is injected. It's an asthma biologic shot. In most cases, physicians dispense Xolair® at a doctor's office or clinic. 

Dosage varies. A patient may only need one shot every four weeks. But, a doctor can prescribe up to two shots every week. 

Xolair® at Home

In 2020, Xolair® developers applied for a new FDA approval. They designed syringes pre-filled with one Xolair® dose. 

Patients can take these pre-measured shots at home. In 2021, the U.S. FDA approved the pre-filled shots. The regulatory group signed-off on at-home Xolair® use.

Doctors may only prescribe at-home Xolair® to appropriate patients. Appropriate patients have no history of anaphylaxis or allergic reactions.

They must also administer the shot correctly three times. The doctor must observe the patient administering the dose before he prescribes the at-home shot. 

Omalizumab rarely causes side effects. The most common side effects include:

• Muscle aches
• Fatigue
• Joint pain
• Injection site irritation or reaction

It's important to talk to your doctor about a drug's potential side effects. They can run down the most likely issues. They can also suggest how to deal with them. 

Eosinophilic asthma is a severe form of asthma. It often resists steroid treatments. 

Immune responses follow different "chains of command" in different bodies. Some patients have a Th-2 dominant inflammatory response.

The Th-2 cell is usually adaptive. It targets immune system responses and helps repair tissue.

But, the response depends on cytokines to deliver messages correctly. Cytokines are proteins and amino acids. One cytokine in this system is Il-5.

Il-5 Dysfunction

When Il-5 is dysfunctional, it doesn't properly relay messages from Th-2. This error causes bone marrow to produce too many eosinophils. Then, too many eosinophil cells are "recruited" to swarm the antigen.

Other command dysfunctions in this chain exacerbate the problem. Airways become hyper-responsive and the system produces too much mucous.

Then, down-the-line cells release too many histamines and other fluids. This causes:

• Acute allergic reactions
• Vasodilation (blood vessels widen)
• Edema (tissues swell due to trapped fluids)
• Bronchospasms (airways narrow)

Eosinophilic asthma attacks cause harm even after they end. Eosinophilic cells hover near the tissue surface, ready for action. 

A new antigen can trigger these leftover cells. This is, in part, why eosinophilic asthma resists steroid treatment.  

GlaxoSmithKline developed Nucala® (mepolizumab). Like omalizumab, mepolizumab is derived from hamster cells.

Mepolizumab is a monoclonal antibody. Specifically, it's an IL-5 antagonist. GSK engineered Nucala® to mend dysfunctional inflammatory response chains.

Mepolizumab binds to IL-5 proteins. Then, it alters the proteins' signals. This prevents the downstream effects of the faulty signal.

As a result, bone marrow does not overproduce eosinophils. There's no eosinophil swarm. 

GSK notes that doctors should prescribe Nucala® alongside corticosteroids. The antibody makes these steroids more effective.  

Nucala® earned FDA approval in 2015. The FDA approved later formulations in 2020 and 2021. Nucala® can treat some blood vessel disorders as well as asthma. 

Nucala® is a shot. Someone must inject the medicine under the patient's skin. 

Initially, only medical professionals could dispense mepolizumab. Also, they had to give the shot in a clinical setting. 

Now, patients can inject themselves at home. Patients take one dose every four weeks. 

Mepolizumab has no known drug interactions. But, there are a few potential side effects to be aware of. These include:

• Fatigue
• Headache
• Back-pain
• Injection site reaction

Studies note other side effects that are incredibly rare. Talk to your doctor about what to do in the case of an extreme effect. 

Teva Pharmaceuticals makes Cinqair®. Scientists used recombinant DNA technology to create the cell line.

They developed Cinqair® from murine myeloma NS0 cells. These cells are used often in biomedicine.  

Doctors dispense Cinqair® through an intravenous (IV) infusion. You cannot administer Cinqair® through an IV push or bolus. 

Dosages vary. Patients take Cinqair® once every four weeks. Only a medical professional in a healthcare setting can administer this drug. 

Cinquair® has more frequent and significant side effects than Nucala and Xolair. The FDA labels Cinqair with its strongest warning. 3.3% of patients have experienced anaphylaxis on this drug. 

Cinqair® increases patients' risk of developing cancer. Patients also risk throat pain. 

AstraZeneca developed Faserna®. Scientists altered this biologic to be lightweight.

Faserna® is an afucosylated antibody. Engineers created previous afucosylated antibodies as anti-cancer agents. 

Faserna® is a shot. Someone must inject Faserna® under the patient's skin. 

Patients may also self-administer Faserna®. The Faserna® Pen earned FDA approval in 2019. 

Initially, patients must take Faserna every four weeks. Then, patients only need a dose once every eight weeks. 

Patients who take Faserna risk anaphylaxis. However, that is not common. Common side effects include:

• Headache
• Sore-throat
• Fever
• Injection-site reactions

Talk to your doctor about potential side effects. Learn what to do in the case of adverse reactions.

Sanofi and Regeneron Pharmaceuticals developed Dupixent®.

They specifically developed dupilumab to reduce dependency on oral steroids. Some patients can reduce or eliminate oral steroids with this biologic.