GIVLAARI® (givosiran)
SIGNIFICANTLY
REDUCED ATTACKS

IN ADULTS WITH AHP1
See the Clinical Efficacy

During the 6-month treatment period of the ENVISION trial, patients with AHP experienced 70% fewer attacks* on average with GIVLAARI vs placebo1

Average number of porphyria attacks: 1.9 (95% CI: 1.3, 2.8) with GIVLAARI vs 6.5 (95% CI: 4.5, 9.3) with placebo

  • Attack rate ratio: GIVLAARI vs placebo 0.3 (95% CI: 0.2, 0.4); P<0.0001

See More Clinical Data

In the 12-month interim analysis of the open-label extension (OLE) of the ENVISION trial, attack* reduction was sustained in patients with AHP continuing treatment with GIVLAARI2

In the OLE, patients who crossed over from placebo to GIVLAARI had reductions in attacks similar to GIVLAARI patients in the double-blind period.

  • Endpoints in the ENVISION OLE are exploratory2

See More Clinical Data

*Attacks requiring hospitalization, urgent healthcare visit, or IV hemin administration at home.1

GIVLAARI targets and causes degradation of ALAS1 mRNA, reducing the production of neurotoxic intermediates ALA and PBG1,3

ALA and PBG are factors associated with attacks and other disease manifestations of AHP

See How GIVLAARI Works

ALA, delta-aminolevulinic acid; ALAS1, delta-aminolevulinic acid synthase 1; mRNA, messenger RNA; PBG, porphobilinogen.

References: 1. GIVLAARI [package insert]. Cambridge, MA: Alnylam Pharmaceuticals, Inc; 2019. 2. Data on file. Alnylam Pharmaceuticals, Inc. 3. Sardh E, Harper P, Balwani M, et al. N Engl J Med. 2019;380(6):549-558.

 

IMPORTANT SAFETY INFORMATION

Contraindications

GIVLAARI® (givosiran) is contraindicated in patients with known severe hypersensitivity to givosiran. Reactions have included anaphylaxis.

Anaphylactic Reaction

Anaphylaxis has occurred with GIVLAARI treatment (<1% of patients in clinical trials). Ensure that medical support is available to appropriately manage anaphylactic reactions when administering GIVLAARI. Monitor for signs and symptoms of anaphylaxis. If anaphylaxis occurs, immediately discontinue administration of GIVLAARI and institute appropriate medical treatment.

Hepatic Toxicity

Transaminase elevations (ALT) of at least 3 times the upper limit of normal (ULN) were observed in 15% of patients receiving GIVLAARI in the placebo-controlled trial. Transaminase elevations primarily occurred between 3 to 5 months following initiation of treatment.

Measure liver function tests prior to initiating treatment with GIVLAARI, repeat every month during the first 6 months of treatment, and as clinically indicated thereafter. Interrupt or discontinue treatment with GIVLAARI for severe or clinically significant transaminase elevations. In patients who have dose interruption and subsequent improvement, reduce the dose to 1.25 mg/kg once monthly. The dose may be increased to the recommended dose of 2.5 mg/kg once monthly if there is no recurrence of severe or clinically significant transaminase elevations at the 1.25 mg/kg dose.

Renal Toxicity

Increases in serum creatinine levels and decreases in estimated glomerular filtration rate (eGFR) have been reported during treatment with GIVLAARI. In the placebo-controlled study, 15% of patients receiving GIVLAARI experienced a renally-related adverse reaction. The median increase in creatinine at Month 3 was 0.07 mg/dL. Monitor renal function during treatment with GIVLAARI as clinically indicated.

Injection Site Reactions

Injection site reactions were reported in 25% of patients receiving GIVLAARI in the placebo-controlled trial. Symptoms included erythema, pain, pruritus, rash, discoloration, or swelling around the injection site. One (2%) patient experienced a single, transient, recall reaction of erythema at a prior injection site with a subsequent dose administration.

Drug Interactions

Concomitant use of GIVLAARI increases the concentration of CYP1A2 or CYP2D6 substrates, which may increase adverse reactions of these substrates. Avoid concomitant use of GIVLAARI with CYP1A2 or CYP2D6 substrates for which minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, decrease the CYP1A2 or CYP2D6 substrate dosage in accordance with approved product labeling.

Adverse Reactions

The most common adverse reactions that occurred in patients receiving GIVLAARI were nausea (27%) and injection site reactions (25%).

INDICATION

GIVLAARI is indicated for the treatment of adults with acute hepatic porphyria (AHP).

For additional information about GIVLAARI, please see full Prescribing Information.