Is self-injectable Benlysta a game-changer?

According to our poll about 5% of our community has tried the IV form of Benlysta. These patients now have a new option, and other patients considering the drug before, might be more open to a medication they can take at home. But does that make it a game changer?

How will self-injectable Benlysta work?

After training from their health care provider, patients will be able to administer the medicine as a once weekly injection of 200mg, from either a single-dose pre-filled syringe or from a single-dose autoinjector.

When will self-injectable Benlysta be available?

GSK hopes it will be available in specialty pharmacies in the US in late August 2017.

Is self-injectable Benlysta effective and safe?

The approval was based on an 836-person clinical trial. 556 patients were given weekly subcutaneous (SC) belimumab 200mg for 52 weeks and compared 280 patients that were given a placebo for the same time frame.

At week 52, the two groups were measured on 3 metrics. The main metric, called the primary endpoint, was the SLE Responder Index (SRI4), which is a complex measure of disease activity. The other two metrics, called secondary endpoints, were reduction in corticosteroid dosage and time to severe flare.

The study concluded: “In patients with moderate-to-severe SLE, weekly SC doses of belimumab 200 mg plus standard SLE therapy significantly improved their SRI4 response, decreased severe disease flares as compared with placebo, and had a safety profile similar to placebo plus standard SLE therapy.”  

You can see all the details and data from the study here.

 Benlysta…

• is given to adults with SLE who are receiving other Lupus medicines.
• works by reducing certain cells in your immune system that can make Lupus active.
• targets specific immune cells in your body, rather than the blanket approach of other therapies that suppress your entire immune system.
• is a biological therapy. Biological therapy involves the use of living organisms or substances derived from living organisms to treat disease.
• is a monoclonal antibody. A monoclonal antibody is a type of protein made in a laboratory that finds and attaches to only one type of substance in the body. It is made to target and destroy only certain cells in the body, which may help protect healthy cells from damage.

Before the development of Benlysta, most treatments (such as steroids, antimalarial medications, immunosupressive drugs, and organ-rejection drugs) were borrowed from treatment for other diseases or conditions.

Type: Biologic infusion

Benlysta is given through IV infusion, meaning it is delivered through a needle placed in a vein by a nurse or health provider. The medicine must be given slowly, so the needle will remain in place for at least 1 hour. Preparation time before the infusion and monitoring time afterwards will vary, depending on what your healthcare professional thinks is best for you.

Your doctor will prescribe a dose and schedule that is appropriate for your Lupus symptoms and your body. The most common schedule is to receive the first three infusions at two week increments, and after that to receive one infusion every four weeks.

Benlysta is a biologic, also known as a biopharmaceutical. These types of medications are synthesized from biological sources and can contain sugars, proteins, nucleic acids, or other living cells.

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Need-to-know Benlysta Info

Before you begin taking Benlysta, you should have an open and honest conversation with your doctor about all aspects of your lupus (if you haven’t already!).

It is not known if Benlysta is safe and effective in people with severe active lupus nephritis or severe active central nervous system lupus, and it has not been studied in combination with other biologics or intravenous cyclophosphamide. Use of Benlysta is not recommended in these situations.

Do not receive Benlysta if you are allergic to belimumab or to any of the ingredients in Benlysta.

Women who are pregnant, may become pregnant, or are breastfeeding should not take Benlysta as it’s not known what effect it may have on an unborn baby or on breastmilk.

The Benlysta label information from the FDA is available here.

Side Effects of Benlysta

Call your doctor right away if you notice any of these side effects:

• Allergic reaction: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness, trouble breathing
• Anxiety, depression, thoughts of hurting yourself
• Change in how much or how often you urinate, bloody or cloudy urine, pain or burning when you urinate
• Chest pain or trouble breathing
• Confusion, memory loss, problems with vision, speech, or walking
• Fever, chills, cough, runny or stuffy nose, sore throat, and body aches
• Lightheadedness, dizziness, or fainting, severe headache
• Pain, itching, burning, swelling, bleeding, or a lump under your skin where the needle is placed

If you notice these less serious side effects, talk with your doctor:

• Diarrhea, nausea
• Trouble sleeping

If you notice other side effects that you think are caused by this medicine, tell your doctor.

The most commonly reported negative reactions with Benlysta are nausea, diarrhea, fever, inflammation of the nose and throat, bronchitis, insomnia, pain in extremity, depression, and migraine.

The FDA label also notes that there were more deaths reported during the clinical trial of those on Benlysta as compared to the placebo groups. In 3 clinical trials, 14 deaths occurred out of 2,133 people enrolled in the trials. 3 deaths occurred in the placebo groups while 11 occurred in the Benlysta groups (which were subdivided based on amount of medication received).

A full list of known side effects can be found here.

Starting Benlysta

Benlysta is administered via intravenous infusion only. Additionally, it must be reconstituted and diluted prior to administration. It should not be administered as an IV push or as a bolus.

Benlysta is delivered as a lyophilized powder and needs to be reconstituted, diluted, and administered by a healthcare professional. For those interested, the directions for that process are available on the FDA label.

The dosage schedule for Benlysta traditionally is:

First 3 doses: 10 mg/kg given every 2 weeks

Subsequent doses: 10 mg/kg given ever 4 weeks

All doses should be administered over the course of roughly an hour, though the infusion rate may be slowed or stopped if there are any reactions.

Drug interactions with Benlysta

A total of 109 drugs are known to interact with methotrexate, including 29 major drug interactions. For a full list that can be easily searched, visit drugs.com

Due to the nature of the medication, the weakened immune system may lead to increased incidence of infection. This also means that many live vaccines have an opportunity to interact with the medication and should be discussed with a doctor. This includes:

• the flu vaccine (administered via mist or shot)
• measles vaccine
• mumps vaccine
• polio virus vaccine
• rotavirus vaccine
• rubella vaccine
• smallpox vaccine
• typhoid vaccine

With regard to medications, there are a number of relatively common medications that people with lupus and other autoimmune diseases should be aware of. The following medications are known to interact strongly with Benlysta (tell you doctor if you are taking, or have taken, any of the following):

• Cimzia (certolizumab)
• Enbrel (etanercept)
• Humira (adalimumab)
• Remicade (infliximab)
• Renflexis (infliximab)

Cost

Benlysta is an expensive medication and is not always covered by insurance.

GoodRx makes the following price estimate for 400 mg of Benlysta:

1 400mg vial costs $1,707.

Lupus and Benlysta research

Benlysta was developed and researched specifically for people with lupus.

The initial clinical trials were able to pool the data for the trial groups because there were no differences in safety at various dosing strengths. Participants received either Benlysta or a placebo as an addition to their standard care.

The population in the initial trial was:

• Average age: 39 years old
• 94% Female
• 52% Caucasian

93% of people in the Benlysta groups experienced an adverse reaction compared to 92% of people in the placebo group. The most common adverse reaction was a serious infection (6% in the Benlysta group compared to 5.2% in the placebo group).

3 clinical trials were used to test for the efficacy of the medication. The first helped researchers define a subpopulation, with a positive autoantibody result for whom the medication could be effective. Future studies limited enrollment to those with positive autoantibody scores and SELENA-SLEDAI scored greater than or equal to 6.

The primary endpoint (necessary measure to equal a successful trial) was a decrease of the SELENA-SLEDAI score of greater than or equal to 4 points. A significantly greater number of people in the Benlysta cohort saw this decrease in disease activity as compared to the placebo group for people taking the 10 mg/kg dose of Benlysta.

There was not a significant difference between the placebo group and the Benlysta cohort at the 76 week mark.

Due to lack of diversity and some variable scores, there are still outstanding questions about the efficacy of Benlysta for black or African-American people with lupus. Additional studies are underway to explore any variability in dosing or effectiveness. The FDA label notes that caution should be used when considering Benlysta as a treatment.

Additionally, the researchers noted that taking Benlysta did not significantly reduce a person’s chance of having a severe flare OR enable a person to take significantly less steroids.

Study Methodology

The OBSErve study was a retrospective, observational cohort study. That means that researchers analyzed health records to see how patients in the real world were responding to Benlysta based on common health indicators like SELENA/SLEDAI scores. Patient records were collected from 6 months prior to the start of Benlysta to 6 months after the start of Benlysta.

Results

78% of patients experienced a 20% or greater increase in overall clinical response as assessed by their physicians

Additionally, objective measures of patient disease status, such as the SELENA/SLEDAI were used to measure common clinical and serological symptoms of lupus.

In total, SELENA/SLEDAI scores decreased from 10.6 to 5.6 in the first 6 months of treatment. The reduction means that the disease was less symptomatic following the start of Benlysta.

Researchers also looked into 6 specific symptoms of lupus: arthritis, fatigue, rash, alopecia, low complement, and increased anti-dsDNA antibody levels. The great majority of patients experienced an improvement to some or all of these symptoms. There was notable improvement of arthritis and rashes. The full report of improvement or worse outcomes by symptom is available here.

Patients receiving belimumab therapy for six months were also able to switch to low dose corticosteroid doses. Low dose treatment is understood to be under 7.5 mg/day of corticosteroid. Typical patient corticosteroid use decreased from 13.7 mg to 7.6 mg; those on high doses of corticosteroids dropped from 17.5 to 8.6 mg after Benlysta treatment.

Other findings of note

6 patients of 102 in the study discontinued treatment of Benlysta during the six months. For 3 of them, the physician-documented discontinue reason was “disease progression” and “ineffective medication.” 1 patient had an allergic reaction – which is consistent with previous findings that approximately 1% of people are allergic to belimumab. Also, one patient passed away, but “no causal relationship to belimumab was suspected.”

There were interesting finding regarding the number of visits per patient to the clinic, hospital, and emergency room as well. While the number of scheduled visits increased per patient so that people could receive their infusions, the number of unscheduled visits decreased overall. That means that there were fewer hospitalizations and ER visits following the start of Benlysta therapy. The full chart if available here.

Participant Profiles

For a full view of baseline patient profiles, click here

102 patient records were collected from 21 sites in Germany in 2013

91% of the participants were female

101 of the participants were Caucasian

Average age of participants was 42.5 years old (with a standard deviation of plus/minus 13.83 years

Average body mass index (BMI) was 25.3 kg/m^2 (standard deviation 6.19 kg/m^2)

85% of participants had Moderate or Severe SLE as determined by disease indices like the SELENA/SLEDAI.

58% of participants had been diagnosed with SLE for over 10 years

Why start Benlysta?

88% of participants started Benlysta because the previous treatments were not effective. And, 61% of people had lupus that was getting worse.

In only 26% of people was Benlysta added because the prior treatment regimen was not tolerated well by participants.