The US FDA has recently unanimously recommended Nucala (Mepolizumab) for add on maintenance treatment in patients 18 years older with severe eosinophilic asthma. The panel recommended against Nucala (mepolizumab) for children aged 12 to 17 years old. Severe eosinophilic asthma is defined as a blood eosinophil count greater than 150 cells/microliters at the start of treatment or greater than 300 anytime the past 12 months.
There are currently no approved treatments for patients with severe asthma with predefined eosinophil levels.
Nucala or Mepolizumab is a humanized monoclonal antibody to human interleukin 5 (IL-5). IL-5 is primarily involved in the regulation of blood and tissue eosinophils. Eosinophils are responsible for airway inflammation in asthma. Thereby by using Nucala (Mepolizumab) which blocks IL-5, this would reduce expression of eosinophils in the blood and tissue.
Nucala (Mepolizumab) is proposed to be administered subcutaneously every 4 weeks. Clinical studies showed a significant reduction in asthma exacerbations in treatment groups receiving Nucala (mepolizumab). The rate of hospitalizations or ER visits was lower in the treatment groups of Nucala (mepolizumab) than the placebo groups.
Side effects seen were local injection site reactions and possibly hypersensitivity reactions with Nucala (mepolizumab). Long term side effects remain to be seen as this drug still hasn’t come out on the market yet.
This would be the second monoclonal antibody drug to come out in the market for severe asthma. Xolair (omalizumab) has been on the market for years and it is used to treat severe persistent asthma. It blocks IgE receptors in the blood and it also has an indication for chronic idiopathic urticaria. It works well in patients who have allergic asthma, but it is very cost prohibitive, in some cases it can be thousands of dollars a month. There is currently no price yet on Nucala (mepolizumab), but most likely it won’t be inexpensive, possibly in the same neighborhood as over a thousand a month. GSK has not given any indication of its cost before launch.
In the pipelines, there is another anti IL-5 monoclonal antibody, it is called Cinquil (Reslizumab) Cinquil This medication likely will be on the market after Nucala (mepolizumab), they both may have the same indication for eosinophilic asthma, or there could be other eosinophilic indications as well.
But for the patients who have severe persistent eosionophilic asthma, who do not respond to conventional asthma medications, Nucala (mepolizumab) may be a good treatment option in the future. You should speak with your allergist or allergy doctor to see if Nucala (mepolizumab) is right for you.
Update: The US and Food and Drug Administration is expected to give its final decision/approval on November 4th. Once it is approved, Nucala (mepolizumab) should be available after November 12th, please check our website for updates on Nucala and what the eosinophil count criteria will need to be to qualify for this medication.
Update, 11/04/2015: As expected, Nucala (mepolizumab) won U.S. regulatory approval to treat severe asthma. It will be a once a month injection for add on therapy for severe asthma. It will be available for patients 12 years and older, as the agency went against its own advisory committee. It should be available shortly and we will publish more information as it becomes available.
11/5/2015: The dosage of Nucala (mepolizumab) will be a 100 mg fixed dose subcutaneous injection every 4 weeks. This is in contrast to Xolair that is also given for asthma, where the dosage depends on a patients IgE level and weight. A patient would qualify for Nucala (mepolizumab) if they have severe asthma, their eosinophil level is 150 cells/mcl or greater (within the past 6 weeks) and 2 asthma exacerbations within the last 12 months.
11/12/15: Glaxo Smith Kline will have a copay assistance program for Nucala (mepolizumab), for eligible patients, they will support up to $9,000 annually. (For those without insurance who would pay out of pocket for Nucala, the minimum yearly cost would be $9,000). Patients must have a private insurance plan, not a state, federal or government plan. It is only eligible for patients who live in the United States, not the District of Columbia, Puerto Rico and the U.S. Virgin Islands. If your commercial insurance payer has opted out of the copay assistance program, you will not be eligible to receive the $9,000 copay assistance.
Nucala (mepolizumab) is now available and your allergy doctor or allergy specialist would be the best physician to speak with whether or not this medicine is best for you. Generally you would have to have severe asthma not controlled with your present medications and your CBC would show your eosinophil count greater than 150 cells/mcl. Being a new medication, insurance coverage will likely be very difficult, but your allergist can help navigate you through the approval process if you have a commercial insurance plan. The cost of Nucala (mepolizumab) without insurance is approximately $2500/month, some reports have said it is $32,500/year ($2708/month). For comparison though, Xolair (omalizumab) which is also given for asthma, a patient can use 1-6 vials a month, and each vial costs approximately $850. Once we have a definitive price for Nucala, we will post the information.
Some insurance companies will allow you to be qualified for Nucala (mepolizumab) if you have an eosinophil count of greater than 300 cells/mcl during the past year, it won’t be necessary to repeat it again prior to starting treatment if it is above that. If it is not above that and you are planning to start treatment, an eosinophil count of greater than 150 cells/mcl would be needed for your insurance company to qualify you to receive Nucala (mepolizumab).
Clearance for Nucala in Europe should happen sometime later this month.
With two different monoclonal antibodies on the market now for asthma, Nucala (mepolizumab) and Xolair (omalizumab), patients have been asking if both medications can be taken together. To date, there has been no studies with both medications, Nucala and Xolair. My opinion on this is, if a patient is already taking Xolair and is seeing good results, they should continue taking the medication. If the patient is on the Xolair and they are not improving after several months of injections, then it may be time to switch to Nucala (mepolizumab). There should be no reason why a patient needs to take both medications to control their asthma, either one should be sufficient and if its not, then they should switch, not add on. But your allergy doctor would be the best person to speak to regarding this, as every patient is unique and different. It is though possible that a patient could have both very high eosinophils and an elevated IgE count and both are triggers for asthma. Some patients have been wondering if they could take both Xolair and Nucala at the same time. The problem with that though is both medications cost thousands of dollars a month and insurance companies are very unlikely to cover both medications. But since each medication has a different mechanism of action, there is no current contraindication to use them at the same time. But I feel it is unnecessary and that the patient and the allergy doctor should decide which one is best for them and not use them together.
Another question that will have to be answered amongst allergists, is if a patient has moderate or severe persistent asthma that is not controlled with medications and you want to give a monoclonal antibody such as Xolair or Nucala, which one do you pick if they qualify for both? That question has yet to be answered, but it will likely depend on what you feel is the most stronger trigger of asthma in the patient, IgE or Eosinophils. Most severe allergic asthma patients will likely have elevated IgE levels and elevated eosinophil counts. There will likely be no studies in the future comparing Nucala vs. Xolair, to see which is the most efficacious between the two. Most likely there will be anecdotal evidence from allergists reporting which medication has worked better on a patient. The Nucala (mepolizumab) studies have shown that the higher the eosinophil count, the more efficacious it is. So if you are deciding between Nucala vs Xolair, if the eosinophil count is very high, Nucala may be a better option. For Xolair, if the IgE count is very high along with very elevated perennial allergens (i.e. dust mites, cats, dogs, mold) and those are the major triggers of your asthma, Xolair (omalizumab) may work better. Although for Xolair (omalizumab) the upper limit of the IgE level is 700 IU/ml, if your IgE level is above that, you would not qualify for Xolair. For Nucala (mepolizumab) there is no upper limit of the eosinophil count to qualify for the medication.
Update 2/14/17: A recent study looked at giving anti IL-5 therapy (in this case Cinqair) to all patients with uncontrolled asthma. Not surprisingly the asthmatic patients who did not have eosinophilia (in this study above 400 eosinophil count), did not improve. This underlies the importance of picking the right patients for anti IL-5 therapy (either Nucala or Cinqair). If the patient does not have eosinophilia, neither of these therapies would work, and most likely the higher the eosinophil count, the better response to one of these medications. So Anti-IL-5 therapy only works at high eosinophil counts.
As with Xolair (omalizumab), Nucala (mepolizumab) may not necessarily work right away. The data from GSK shows a significant improvement around 4 months, meaning 4 injections. Other studies showed improvement of symptom scores at 6 months. As with all medications and patients, everyone responds differently, some patients can respond earlier or even later. A study was done on Xolair for hives and sometimes it can take over 6 injections to see improvement of hives and others can respond in 1 or 2 days. Xolair
As with any medication, especially injectables, there can be side effects. The most common adverse events of Nucala (mepolizumab) are nasopharyngitis, headache, upper respiratory infection, sinusitis, bronchitis, oropharyngeal pain and injection site reactions. Nucala’s side effects are similar to Xolair’s (omalizumab). After market, Xolair was linked to delayed onset anaphylaxis (0.09-0.2%). There is no data that shows Nucala (mepolizumab) causing anayphlaxis reactions currently.
Update February 22, 2017
Assessing the Cost-Effectiveness of Mepolizumab (Nucala)
A recent study published in the Annals of Allergy Asthma Immunology, looked into adding Nucala to standard treatment with inhaled steroids and controller medication in patients with severe asthma disease and increased eosinophils. They looked into the cost effectiveness of adding mepolizumab. Given the whole sale cost of mepolizumab of $2500/month, annual cost of $32,500/year, the authors also estimated that 24 exacerbations over a lifetime were averted per patient receiving the treatment. Avoidance of exacerbations and decrease in long-term oral steroid use resulted in more than $18,000 in cost offsets among those receiving Nucala.
The authors stated that for Nucala to achieve cost effectiveness, significant discounts would be needed from the current list price. Although adding Nucala to treatment for adult asthma patients with severe eosinophilic asthma appears to confer clinical benefits in lower rates of exacerbation and improved quality of life, the costs are very high. These factors will all be important for physicians and large national insurers to take into account when deciding to treat a patient with Nucala.
A limitation of this study is that the overall improved quality of life was not taken into affect from having decreased asthma exacerbations, this study just looked at the financial components of using Mepolizumab versus not using it. Also it assumed the whole sale price of Nucala was using being used ($2500), prescription drug plans may negotiate a lower rate for their members.
Link to Cinquil Now known as Cinaqair. Click on link for comparisons of Cinqair vs. Nucala
Link to Dupilumab
Link to Lebrikizumab
Nucala has 4 official therapeutic indications to date:
- Severe Eosinophilic asthma
- Eosinophilic granulomatosis with polyangiitis
- Hyperesosinophilic syndrome
- Chronic rhinosinusitis with nasal polyps
Other studies are currently underway for other indications.