Important Safety Information:

VIJOICE® (alpelisib) tablets is contraindicated in patients with severe hypersensitivity to alpelisib or any of its ingredients...

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Indication: VIJOICE® (alpelisib) tablets is indicated for the treatment of adult and pediatric patients 2 years of age and older with severe manifestations of PIK3CA-Related Overgrowth Spectrum (PROS) who require systemic therapy.

This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Efficacy

Lesion Response

FDA approval for VIJOICE® (alpelisib) tablets was based on a real-world study of PIK3CA-Related Overgrowth Spectrum (PROS)1

Takeaways from a real-world study of PIK3CA-Related Overgrowth Spectrum

CLOVES, congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal and spinal; MCAP or M-CM, megalencephaly-capillary malformation; KTS, Klippel-Trenaunay syndrome; FIL, facial infiltrating lipomatosis.

More information about this real-world study of PROS1:

The single-arm clinical study followed a structured protocol to allow for proper data analysis

  • 57 patients 2 years of age and older with PROS received VIJOICE as part of a compassionate use program. A total of 58 patients were eligible for inclusion, but 1 patient withdrew consent; therefore, 57 patients were included in the full study population3
    • The study included 39 pediatric patients and 18 adult patients
    • Response was confirmed by BICR
    • Eligible patients had clinical manifestations of PROS that were assessed by the treating HCP as severe or life-threatening and necessitating systemic treatment
  • The efficacy population (n=37), which was a subset of the full study population, included patients who had at least 1 target lesion on imaging performed within 24 weeks prior to receipt of the first dose of VIJOICE
    • 32 patients from the efficacy population without a missing response* at Week 24 or 6 months (+/- 4 weeks) were used for the analysis of the primary end point (complete case analysis). One patient with a scan at index discontinued prior to Week 24 and was not included in the analysis3

Primary end point

  • Response at Week 24, defined as the proportion of patients achieving a ≥20% reduction from baseline in the sum of measurable target lesion volume (1 to 3 lesions) confirmed by at least 1 subsequent imaging assessment, provided that:
    • None of the individual target lesions had a ≥20% increase from baseline
    • Nontarget lesions had not progressed, and
    • There were no new lesions

Select secondary end points3

  • Changes in the sum of measurable target lesion volume (1 to 3 lesions) over time, as determined by BICR
  • Changes in PROS signs and symptoms, and complications over time
  • Changes in performance status over time
  • Assessment of PROS-related surgeries over time
  • Duration of response, defined as the time from the first documented response to the date of the first documented disease progression or death due to any cause

*Patients were considered as having a missing response if lesion volume(s) assessment at Week 24 or 6 months (+/- 4 weeks) was not available and they did not permanently discontinue VIJOICE prior to 24 weeks of treatment and did not require surgery as rescue therapy between the index date and 24 weeks of treatment with VIJOICE due to disease deterioration.
BICR, blinded independent central review; HCP, health care professional.

 

VIJOICE shrunk overgrowth1

27% of patients experienced a response at Week 24. Patients maintained response

Response was defined as the proportion of patients achieving a ≥20% reduction from baseline in the sum of measurable target lesion volume (1 to 3 lesions) confirmed by at least 1 subsequent imaging assessment, provided that none of the individual target lesions had a ≥20% increase from baseline, nontarget lesions had not progressed, and there were no new lesions.

*Confirmed response as determined by BICR.
Patients without any response assessment at Week 24 were considered nonresponders.

 

In an exploratory analysis of the EPIK-P1 study,
More than 70% of patients experienced any overgrowth reduction3

74.2% of patients experienced any reduction in the sum of target lesion volume

The analysis included patients who had a radiological investigation at Week 24 (n=31). Not all patients with lesion volume reduction were confirmed with a subsequent imaging assessment.

No progression icon

No progression or progression-related surgery at Week 24

  • No patients treated with VIJOICE experienced disease progression
No new lesions icon

No new lesions

  • No patient developed a new lesion while receiving VIJOICE during the study

 

Sign and Symptom Improvement

In an exploratory analysis of the EPIK-P1 study,
Improvements in the most common PROS signs and symptoms were observed3

Percentage of patients with improvements at Week 24 in the most commonly reported signs and symptoms

Graphs showing how VIJOICE improved pain, vascular malformations, fatigue, limb asymmetry, and disseminated intravascular coagulation in PROS patients

Improvement was defined based on CTCAE version 4.03 grade reduction or resolution of the event. Percentages were calculated based on the number of patients who reported the event at baseline.

CTCAE, Common Terminology Criteria for Adverse Events.

Pediatric patients experienced substantial sign and symptom improvement3

Sign and symptom improvement in pediatric patients

CTCAE, Common Terminology Criteria for Adverse Events.

Adult patients experienced substantial sign and symptom improvement3

Sign and symptom improvement in adult patients

CTCAE, Common Terminology Criteria for Adverse Events.

 

Functional Improvements

In an exploratory analysis of the EPIK-P1 study,
Improvements in functionality were
observed3

 

 ~30% (14/47) of patients experienced functional improvements at Week 24

Performance status was recorded at baseline for 47 patients (33 pediatric patients; 14 adult patients) using ECOG, Karnofsky, and Lansky assessments.

For the ECOG scale, improvement is defined as a decrease by at least 1 point and worsening is defined as an increase by at least 1 point. For the Karnofsky and Lansky scales, improvement is defined as an increase by at least 20 points and worsening is defined as a decrease by at least 20 points. 

The performance status score was stable in 10 patients (21%), and it was not reported for 23 of the 47 patients at Week 24.

Level of functioning icon

ECOG scales assess level of functioning by measuring a patient’s4:

  • Daily activity
  • Physical ability
  • Ability to care for oneself
Patient assessment scales icon

Lansky and Karnofsky scales assess a patient’s4,5:

  • Ability to perform normal activities of daily living
  • Functional status

ECOG, Eastern Cooperative Oncology Group.

 

References:

  1. Vijoice [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2022.
  2. Study assessing the efficacy, safety and PK of alpelisib (BYL719) in pediatric and adult patients with PIK3CA-related Overgrowth Spectrum. ClinicalTrials.gov identifier: NCT04589650. https://clinicaltrials.gov/ct2/show/NCT04589650. Updated March 2, 2022. Accessed March 15, 2022.
  3. Data on file. CBYL719F12002 clinical study report. Novartis Pharmaceuticals Corp; 2021.
  4. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-655.
  5. Lansky SB, List MA, Lansky LL, Ritter-Sterr C, Miller DR. The measurement of performance in childhood cancer patients. Cancer. 1987;60(7):1651-1656.

INDICATION

VIJOICE® (alpelisib) tablets is indicated for the treatment of adult and pediatric patients 2 years of age and older with severe manifestations of PIK3CA-Related Overgrowth Spectrum (PROS) who require systemic therapy.

This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

IMPORTANT SAFETY INFORMATION

VIJOICE is contraindicated in patients with severe hypersensitivity to alpelisib or any of its ingredients.

Severe Hypersensitivity. Severe hypersensitivity reactions, including anaphylaxis and anaphylactic shock, have occurred in adult patients treated with alpelisib in the oncology setting and may occur in patients treated with VIJOICE. VIJOICE is not approved for use in the oncology setting. Permanently discontinue VIJOICE in the event of severe hypersensitivity.

Severe Cutaneous Adverse Reactions (SCARs). SCARs, including Stevens-Johnson syndrome (SJS), erythema multiforme (EM), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), have occurred in adult patients treated with alpelisib in the oncology setting and may occur in patients treated with VIJOICE. If signs or symptoms of SCARs occur, interrupt VIJOICE until the etiology of the reaction has been determined. Consultation with a dermatologist is recommended. If a SCAR is confirmed, permanently discontinue VIJOICE. If a SCAR is not confirmed, VIJOICE may require dose modifications, topical corticosteroids, or oral antihistamine treatment.

Hyperglycemia. Severe hyperglycemia, in some cases associated with hyperglycemic hyperosmolar nonketotic syndrome (HHNKS) or fatal cases of ketoacidosis, has occurred in adult patients treated with alpelisib in the oncology setting and may occur in patients treated with VIJOICE.

In the EPIK-P1 study, grade 1 or 2 hyperglycemia was reported in 12% of patients treated with VIJOICE.

Before initiating treatment with VIJOICE, test fasting plasma glucose (FPG), HbA1c, and optimize blood glucose. After initiating treatment with VIJOICE, monitor fasting glucose (FPG or fasting blood glucose) at least once every week for the first 2 weeks, then at least once every 4 weeks, and as clinically indicated. Monitor HbA1c every 3 months and as clinically indicated. Monitor fasting glucose more frequently for the first few weeks during treatment with VIJOICE in patients with risk factors for hyperglycemia, such as obesity (body mass index ≥30), elevated FPG, HbA1c at the upper limit of normal or above, use of concomitant systemic corticosteroids, or age ≥75.

If a patient experiences hyperglycemia after initiating treatment with VIJOICE, monitor fasting glucose as clinically indicated and at least twice weekly until fasting glucose decreases to normal levels. During treatment with antihyperglycemic medication, continue monitoring fasting glucose at least once a week for 8 weeks, followed by once every 2 weeks, and as clinically indicated. Consider consultation with a health care provider with expertise in the treatment of hyperglycemia, and counsel patients on lifestyle changes.

The safety of VIJOICE in patients with type 1 and uncontrolled type 2 diabetes has not been established. Patients with a history of diabetes mellitus may require intensified hyperglycemic treatment. Closely monitor patients with diabetes.

Interrupt, reduce the dose of, or permanently discontinue VIJOICE based on severity.

Pneumonitis. Severe pneumonitis, including acute interstitial pneumonitis and interstitial lung disease, has occurred in adult patients treated with alpelisib in the oncology setting and may occur in patients treated with VIJOICE.

In patients who have new or worsening respiratory symptoms or are suspected to have developed pneumonitis, interrupt VIJOICE immediately and evaluate the patient for pneumonitis. Consider a diagnosis of noninfectious pneumonitis in patients presenting with nonspecific respiratory signs and symptoms, such as hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic examinations and in whom infectious, neoplastic, and other causes have been excluded by means of appropriate investigations.

Permanently discontinue VIJOICE in all patients with confirmed pneumonitis.

Diarrhea. Severe diarrhea, including cases resulting in dehydration and acute kidney injury, has occurred in adult patients treated with alpelisib in the oncology setting and may occur in patients treated with VIJOICE. In the EPIK-P1 study, 16% of patients experienced grade 1 diarrhea during treatment with VIJOICE. Interrupt, reduce the dose of, or permanently discontinue VIJOICE based on severity.

Embryo-Fetal Toxicity. Based on findings in animals and its mechanism of action, VIJOICE can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with VIJOICE and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use condoms and effective contraception during treatment with VIJOICE and for 1 week after the last dose.

The most common adverse reactions (all grades, incidence ≥10%) were diarrhea (16%), stomatitis (16%), and hyperglycemia (12%).

The most common laboratory abnormalities (all grades, incidence ≥20%) were decreased calcium (corrected) (60%), decreased phosphate (59%), increased glucose (56%), increased HbA1c (38%), increased creatinine (31%), increased bilirubin (29%), decreased magnesium (26%), increased potassium (24%), decreased leukocyte (22%), decreased lymphocyte (20%), and decreased hemoglobin (20%).

Please see full Prescribing Information for VIJOICE® (alpelisib) tablets.