YEARS OF
REAL-WORLD
USE1
SHRINK NF1 PN by ≥20%* and grow their world2
KOSELUGO®(selumetinib) is the FIRST FDA-approved
treatment
for pediatric patients 2 years of age and older
who have neurofibromatosis
type 1 (NF1) and symptomatic,
inoperable plexiform neurofibromas (PN).1,2
Proven to shrink NF1 PN with evidence from long-term data2-4
Review the evidence*
Individual results may vary. 66% (33/50) of patients achieved
the primary endpoint of overall response rate (ORR), defined
as the percentage of patients with complete response (defined
as disappearance of the target PN) or confirmed partial
response (defined as a decrease in target PN volume ≥20% from
baseline and confirmed at a subsequent tumor assessment within
3 to 6 months) at DCO June 2018.2
A subsequent long-term follow-up study was included (DCO
February 2021).4
DCO=data cutoff.
Sam, age 10, living with NF1 PN.
Shown here with his dad. Sam is a Koselugo patient.
Established safety4
In the long-term follow-up, the median duration of exposure with Koselugo was 4.4 years. During this time, no new safety signals were identified.‡
Koselugo treatment timeline
View a timeline of what a patient's first year of response and adverse reactions could look like while on Koselugo.
‡This statement reflects exposure to Koselugo in 74 pediatric patients who received a dosage ranging from 20 mg/m2 to 30 mg/m2 orally twice daily in SPRINT Phase 1 and Phase 2 Stratum 1. At the DCO of February 2021, the median duration of exposure was 4.4 years (range 28 days to 7.7 years). No new safety signals were identified compared to the earlier publications.2,4
Hear from a real Koselugo caregiver and patient
Meet Kim and her son Quentin, a Koselugo patient for over 10 years. Watch Kim reflect on Quentin’s journey with NF1 PN, beginning with his diagnosis at just 22 months old.
Kim:
This is my son, Quentin.
He’s a cool kid. He’s just really cool.
Quentin and his brother are a little bit competitive. But they get along really well. They’ve got each other’s backs.
Quentin is a fighter, for sure. At a very young age, he was diagnosed with Neurofibromatosis type 1 (NF1) related plexiform neurofibromas or PN, benign tumors that can grow along nerves anywhere in the body.
NF1 is his diagnosis. But that does not define who he is as a person.
At about 17 months, he developed a cluster of, at the time, I didn’t know neurofibromas on his cheek.
So, I brought it up to his physician and eventually she recommended an MRI, and it came back that he has Neurofibromatosis (NF1).
He was diagnosed with PN at 22 months. With PN, even with debulking, the tumor can grow back. It would grow in 23% to 33% in volume every three to six months.
Quentin’s tumor got so large that I could put it in the palm of my hand.
He’s had 10 surgeries and countless complications.
Sometimes we cry together. And we have really hard conversations about where NF takes you, you know, and things that he has to deal with. That is really hard, and you compartmentalize it. You become, at that point you’re a caregiver and not a parent.
I mean even now he gets stares. You know one time somebody asked my older son if he punched him in the face.
His brother is definitely his protector, probably one of the best educators and advocates he could ever have.
When Quentin was 5, our doctor told us about a new trial for a drug called selumetinib which would later be called KOSELUGO®.
The doctors told us about possible side effects, including the most common ones such as vomiting and stomach pain.
They felt that KOSELUGO could potentially decrease the size of his tumors. He had to do the preliminary testing and all of that first, but we signed on.
Quentin was 1 of 50 patients that were on the original trial. After FDA approval, whenever there were any questions along the way, we could utilize OneSource.
Which is a free, personalized patient support program offered by Alexion. OneSource was amazing. Because as a parent you’re juggling so many things and then you add that on top of it to know that there is an advocate for you and a resource that you can go to, it’s, it’s very nice to have.
KOSELUGO’s definitely been a good fit for Quentin. He just had an MRI a month ago, and he is stable. Stable is beautiful.
He takes KOSELUGO every 12 hours, so twice a day and it’s part of life.
Quentin’s side effects with KOSELUGO have, they’ve been pretty minimal. He did have some diarrhea. He did have some issues with acne.
Of course, this has been Quentin’s experience, and others may have a different experience with KOSELUGO.
Quentin:
Since taking KOSELUGO, I’ve noticed a big difference in my tumor growth.
I feel like I can do everything almost anybody else can.
Kim:
Quentin is in a good place now, emotionally, and mentally. I feel like he is living his best life.
We still have doctor appointments, but it’s very secondary. It is a sense of relief that he’s on KOSELUGO, that we could breathe a little.
I love being a mom, it’s one of the most rewarding things I think a person could ask for. I can’t imagine not having them.
And I’m so thankful for all KOSELUGO has done for him.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Cardiomyopathy. A decrease in left
ventricular ejection fraction (LVEF) ≥10% below baseline occurred
in pediatric
patients who received Koselugo in SPRINT with some
experiencing decreased LVEF below the institutional lower limit of normal
(LLN), including one patient with Grade 3. All patients with decreased
LVEF were asymptomatic and identified during routine echocardiography.
The safety of Koselugo has not been established in patients with a history
of impaired LVEF or a baseline ejection fraction that is below the institutional
LLN. Assess ejection fraction by echocardiogram prior to initiating treatment,
every 3 months during the first year of treatment, every 6 months thereafter,
and as clinically indicated. Withhold, reduce dose, or permanently discontinue
Koselugo based on severity of adverse reaction. In patients who interrupt
Koselugo for decreased LVEF, obtain an echocardiogram or a cardiac MRI
every 3 to 6 weeks. Upon resolution of decreased LVEF, obtain an echocardiogram
or a cardiac MRI every 2 to 3 months.
Ocular Toxicity. Blurred vision,
photophobia, cataracts, and ocular hypertension
occurred. Retinal
pigment epithelial detachment (RPED) occurred in the pediatric population
during treatment with single agent Koselugo and resulted in permanent discontinuation.
Conduct ophthalmic assessments prior to initiating Koselugo, at regular
intervals during treatment, and for new or worsening visual changes. Permanently
discontinue Koselugo in patients with retinal vein occlusion (RVO). Withhold
Koselugo in patients with RPED, conduct ophthalmic assessments every 3
weeks until resolution, and resume Koselugo at a reduced dose.
Gastrointestinal Toxicity. Diarrhea
occurred, including Grade 3. Diarrhea resulting in permanent discontinuation,
dose interruption or dose reduction occurred. Advise patients to start
an anti-diarrheal agent (eg, loperamide) and to increase fluid intake immediately
after the first episode of diarrhea. Withhold, reduce dose, or permanently
discontinue Koselugo based on severity of adverse reaction.
Skin Toxicity. Rash occurred in 91% of 74 pediatric patients. The most frequent rashes included dermatitis acneiform (54%), maculopapular rash (39%), and eczema (28%). Grade 3 rash occurred, in addition to rash resulting in dose interruption or dose reduction. Monitor for severe skin rashes. Withhold, reduce dose, or permanently discontinue Koselugo based on severity of adverse reaction.
Increased Creatine Phosphokinase (CPK). Increased CPK occurred, including Grade 3 or 4 resulting in dose reduction. Increased CPK concurrent with myalgia occurred, including one patient who permanently discontinued Koselugo for myalgia. Obtain serum CPK prior to initiating Koselugo, periodically during treatment, and as clinically indicated. If increased CPK occurs, evaluate for rhabdomyolysis or other causes. Withhold, reduce dose, or permanently discontinue Koselugo based on severity of adverse reaction.
Increased Levels of Vitamin E and Risk of Bleeding. Koselugo capsules contain
vitamin E which can inhibit platelet
aggregation and antagonize vitamin K-dependent clotting factors. Supplemental
vitamin E is not recommended if daily vitamin E intake (including the amount
of vitamin E in Koselugo and supplement) will exceed the recommended or
safe limits due to increased risk of bleeding. An increased risk of bleeding
may occur in patients who are coadministered vitamin-K antagonists or anti-platelet
antagonists with Koselugo. Monitor for bleeding in these patients and increase
international normalized ratio (INR) in patients taking a vitamin-K antagonist.
Perform anticoagulant assessments more frequently and adjust the dose of
vitamin K antagonists or anti-platelet agents as appropriate.
Embryo-Fetal Toxicity. Based on
findings
from animal studies, Koselugo can cause fetal harm when
administered during pregnancy. In animal studies, administration of selumetinib
to mice during organogenesis caused reduced fetal weight, adverse structural
defects, and effects on embryo-fetal survival at approximate exposures
>5 times the human exposure at the clinical dose of 25 mg/m2 twice daily.
Advise patients of reproductive potential of the potential risk to a fetus
and to use effective contraception during treatment with Koselugo and for
1 week after the last dose.
ADVERSE REACTIONS
Common adverse reactions ≥40% include vomiting, rash (all), abdominal pain, diarrhea, nausea, dry skin, musculoskeletal pain, fatigue, pyrexia, acneiform rash, stomatitis, headache, paronychia, and pruritus.
DRUG INTERACTIONS
Effect of Other Drugs on Koselugo
Concomitant use of Koselugo with a strong or moderate CYP3A4 inducer decreased selumetinib plasma concentrations, which may reduce Koselugo efficacy. Avoid concomitant use with Koselugo.
SPECIAL POPULATIONS
Pregnancy & Lactation. Verify the
pregnancy status of patients of reproductive potential prior to
initiating Koselugo. Due to the potential for adverse reactions in a breastfed
child, advise patients not to breastfeed during treatment with Koselugo
and for 1 week after the last dose.
INDICATION
KOSELUGO is indicated for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN).
To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca
1-800-236-9933
or at
https://us-aereporting.astrazeneca.com
or FDA at
1-800-FDA-1088 or
www.fda.gov/
medwatch.
Please see full Prescribing Information for Koselugo® (selumetinib).
References:
1. Koselugo (selumetinib) approved in US for paediatric patients with neurofibromatosis type 1 plexiform neurofibromas. AstraZeneca. April 13, 2020. Accessed December 4, 2023. https://www.astrazeneca.com/media-centre/press-releases/2020/koselugo-selumetinib-approved-in-us-for-paediatric-patients-with-neurofibromatosis-type-1-plexiform-neurofibromas.html#
2. Koselugo. Package insert. AstraZeneca Pharmaceuticals LP.
3. Data on File, REF-36657, AstraZeneca Pharmaceuticals LP.
4. Gross AM, Dombi E, Wolters PL, et al. Long-term safety
and efficacy of selumetinib in children with neurofibromatosis type 1 on
a phase 1/2 trial for inoperable plexiform neurofibromas. Neuro Oncol. 2023;25(10):1883-1894. doi:10.1093/
neuonc/noad086