Givlaari (givosiran)
An approved treatment for Acute Hepatic Porphyria.
The same compound appears under different names depending on the context. Here is how to identify Givosiran wherever you encounter it, plus the key facts at a glance.
- Generic name
- Givosiran
- Brand name
- Givlaari
- Development code
- ALN-AS1
- Drug class
- RNA interference therapy (ALAS1-directed siRNA)
- Manufacturer
- Alnylam Pharmaceuticals
- How it's taken
- Subcutaneous injection once a month, given by a healthcare professional
The only FDA-approved medicine that prevents acute hepatic porphyria attacks rather than treating them once they start. A once-monthly injection under the skin for adults, given by a healthcare professional, that silences the liver gene behind the toxic buildup.
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Where Givosiran fits
Givlaari is the preventive option for adults whose attacks keep coming back despite trigger avoidance; it does not treat an attack that is already under way, which is Panhematin's role, and the 2 are often used together (hemin for breakthrough attacks). People with rare or mild attacks are usually managed with trigger avoidance and the drug safety database alone.
How Givosiran works
In every acute hepatic porphyria the liver's first heme-making enzyme, ALAS1, runs too fast whenever something pushes the liver to make more heme, and the early building blocks aminolevulinic acid (ALA) and porphobilinogen (PBG) pile up and poison nerves[1]. Givosiran is a short double strand of RNA attached to a sugar (GalNAc) that liver cells pull inside.
Once there, it tells the cell's own RNA interference machinery to destroy the messenger RNA for ALAS1, so the cell makes much less of the enzyme and ALA and PBG fall[1]. One dose keeps working for about a month, which is why it is given monthly. The label describes the effect as reducing the elevated liver ALAS1 mRNA and lowering circulating ALA and PBG, the factors associated with attacks and other disease manifestations of AHP[1].
Mechanism: Small interfering RNA (siRNA) linked to N-acetylgalactosamine (GalNAc) that enters liver cells and degrades ALAS1 messenger RNA through RNA interference, lowering the ALA and PBG that drive attacks
Side effects and safety
- Anaphylaxis. Under 1% in trials; injections are given where allergic emergencies can be treated, and the drug is stopped for good if anaphylaxis occurs.
- Liver toxicity. ALT at least 3 times normal in 15%, mostly in months 3 to 5. Liver tests before starting, monthly for 6 months, then as needed; the dose may be cut to 1.25 mg/kg after a rise improves.
- Kidney effects. Creatinine rises and eGFR falls in 15% of the trial group (median creatinine rise 0.07 mg/dL at month 3); kidney function is monitored.
- Injection site reactions. In 25%, almost all mild; rotate sites and avoid skin that is red, swollen or scarred.
- Raised blood homocysteine. In 16% during the extension; baseline level, then folate, B12 and B6 checks and a possible B6 supplement if it is high.
- Pancreatitis. Reported after approval, some cases severe; new upper abdominal pain or raised pancreatic enzymes should be evaluated, with interruption for severe cases.
- Drug interactions. Raises levels of sensitive CYP1A2 and CYP2D6 substrates; avoid the ones where a small change could be dangerous, or lower their dose.
- Liver function tests before starting, every month for the first 6 months, then as clinically indicated
- Kidney function during treatment
- Blood homocysteine before starting and during treatment
- Observation for allergic reactions at each injection
- Actual body weight at each visit, because the dose is weight-based
The label has no boxed warning but 6 warnings. Anaphylaxis occurred in under 1% of trial patients, so it must be given where medical support is available[1]. Liver enzyme (ALT) rises of at least 3 times the upper limit of normal occurred in 15% of patients in the placebo-controlled trial, mostly between months 3 and 5; liver tests are checked before starting, monthly for the first 6 months and then as needed, and the dose can be halved to 1.25 mg/kg after a rise settles[1].
Kidney effects (a rise in creatinine or a fall in eGFR) were reported in 15% of the givosiran group, with a median creatinine rise of 0.07 mg/dL at month 3, and kidney function is monitored during treatment[1]. Injection site reactions, redness, pain, itching, rash, discoloration or swelling, affected 25% and were mild in 11 of 12 people who had them; 1 person had a brief recall reaction at an earlier site[1].
Blood homocysteine rose in 16% of patients during the open-label extension; the label asks for a baseline level and, if it is high, checking folate, B12 and B6 and considering a B6 supplement[1]. Acute pancreatitis, some cases severe, has been reported since approval, so new upper abdominal pain on Givlaari should not be assumed to be a porphyria attack[1].
In the 6-month placebo-controlled part of ENVISION the most common reactions were nausea (27% vs 11% on placebo) and injection site reactions (25% vs 0%), followed by rash (17% vs 4%), creatinine increase (15% vs 4%), transaminase elevations (13% vs 2%) and fatigue (10% vs 4%); 1 patient stopped permanently for raised liver enzymes[1]. Givosiran also raises blood levels of medicines cleared by CYP1A2 and CYP2D6, so some drugs may need a lower dose[1].
This is not a complete list of side effects. Talk to your doctor or pharmacist about what to expect and when to seek medical attention.
Taking Givosiran
Givlaari is injected under the skin once a month by a healthcare professional; it is not approved for self-injection[1]. The dose is 2.5 mg/kg of actual body weight, drawn from a single-dose vial that holds 189 mg in 1 mL, so most adults need less than 1 vial per dose and anyone needing more than 1.5 mL gets the dose split between 2 syringes and 2 sites at least 2 cm apart[1].
Sites are the abdomen (avoiding a 5 cm circle around the navel), the back or side of the upper arms, or the thighs, rotated each month[1]. A missed dose is given as soon as possible and the monthly schedule restarts from that day[1]. If liver enzymes rise sharply and then improve after a pause, the dose is restarted at 1.25 mg/kg and can go back to 2.5 mg/kg if the enzymes stay settled[1].
Vials are stored at 2 to 25 C (36 to 77 F) in the carton and need no mixing or dilution[1]. Alnylam keeps a treatment center directory on Givlaari.com for finding a site that gives the injections[9].
Availability and cost
Only available as the brand-name product.
An orphan RNA interference biologic for a disease with a few thousand treated patients, made by chemical synthesis of modified RNA strands and dosed by weight once a month for as long as attacks remain a risk. No primary source for the US price was reviewed for this page.
Help paying for Givlaari
Pick your insurance to see which help fits. Drugmaker copay cards can't be used with Medicare, Medicaid or TRICARE; charity funds are the usual route there.
- Copay help
Alnylam Assist Copay Program covers certain out-of-pocket costs for eligible patients with commercial insurance. A case manager enrolls you automatically after your doctor submits a Start Form. Not for Medicare, Medicaid or other government-sponsored insurance; administration costs are not covered where the law prohibits it. The page does not state a dollar cap.
For: private insurance · source - Bridge or quick-start supply
Programs that may help if there is a delay or change in insurance coverage; a case manager decides which program fits after the Start Form is submitted.
For: private insurance, Medicare, Medicaid, TRICARE · source - Free medicine program
Alnylam Assist Patient Assistance Program provides access to treatment at no cost for eligible patients, primarily those who are uninsured. A case manager assesses eligibility after the Start Form is submitted.
For: no insurance, underinsured · source - Insurance and case manager help
After the doctor submits a Start Form, an Alnylam Case Manager contacts the patient within 2 business days with a summary of insurance benefits and starts support. Alnylam also points uninsured and underinsured patients to an independent foundation finder (AHP.support.reassist.us); the foundations are not run by Alnylam.
For: private insurance, Medicare, Medicaid, TRICARE, no insurance, underinsured · source
Good to know: Everything runs through the Start Form your doctor submits. Alnylam says patients must meet eligibility criteria and that it can change or end any program. No dollar maximum for the copay program is published on the page. Givlaari is given by a healthcare professional, so check whether the administration fee is covered separately.
Access and eligibility
Approved for adults with any of the 4 acute hepatic porphyrias (AIP, HCP, VP or ADP). ENVISION enrolled people with at least 2 attacks in the previous 6 months, so it is studied and prescribed for recurrent attacks, not for carriers who have never had one. Safety and effectiveness in children have not been established.
Source: Alnylam Assist
Access program details are provided for informational purposes and may vary based on insurance coverage, geographic location, and individual circumstances. Confirm current eligibility directly with the manufacturer or your specialty pharmacy.
How acute hepatic porphyria treatments compare
Acute hepatic porphyria has 2 FDA-approved medicines that do different jobs. Panhematin (hemin) is infused into a vein in the hospital to stop an attack that has already started, and has been used since 1983. Givlaari (givosiran), approved in 2019, is a monthly injection that prevents attacks in adults who keep having them, and people taking it still receive Panhematin for breakthrough attacks. Your porphyria specialist will weigh how often you have attacks, your liver and kidney tests, and how far you live from a hospital that stocks hemin.
Acute Hepatic Porphyria has 2 FDA-approved treatments: Givlaari (givosiran, approved 2019); Panhematin (hemin for injection, approved 1983). Givlaari is typically used as prevention for adults with recurrent attacks (the trial required at least 2 attacks in 6 months); not for treating an attack in progress and not approved for children.
| Drug | How it works | How it's given | How often | Where you get it | Who it is for | FDA approval |
|---|---|---|---|---|---|---|
Givlaari givosiran You are here | Small interfering RNA that silences the liver's ALAS1 gene so far less ALA and PBG are made | Subcutaneous injection given by a healthcare professional (2.5 mg/kg) | Once a month, ongoing | Clinic or infusion center visit each month | Prevention for adults with recurrent attacks (the trial required at least 2 attacks in 6 months); not for treating an attack in progress and not approved for children | 2019 |
Panhematin hemin for injection | Heme from human red blood cells that replenishes the liver's heme supply and switches ALAS1 off during an attack | IV infusion over at least 30 minutes into a large arm vein or central line (3 to 4 mg/kg a day in practice) | Once a day, sometimes every 12 hours, for 3 to 14 days per attack | Hospital, or an infusion center or doctor's office; most hospitals must order it overnight | Treatment of a confirmed attack (raised urine PBG); the label indication is recurrent attacks of AIP tied to the menstrual cycle in women after carbohydrate therapy is inadequate, and specialists use it for confirmed attacks in all 4 acute porphyrias | 1983 |
This chart is for education only and is not medical advice. Dosing, warnings and who each medicine is approved for come from the FDA prescribing information; statements about how specialists use Panhematin beyond its label wording come from NORD and the American Porphyria Foundation. A porphyria attack is a medical emergency: go to the hospital, and talk with a porphyria specialist about your own treatment plan.
Clinical trial results
ENVISION (NCT03338816) was a randomized, double-blind, placebo-controlled trial in 94 people with AHP (89 with AIP, 2 with VP, 1 with HCP and 2 with no identified mutation) who had at least 2 attacks needing hospital care, an urgent visit or home IV hemin in the previous 6 months[1]. The median age was 37.5 years (19 to 65) and 89% were women.
Over 6 months the mean rate of such attacks was 1.9 on Givlaari against 6.5 on placebo, a 70% reduction (95% CI 60% to 80%, p under 0.0001), and days of hemin use fell from 12.8 to 4.7[1]. In the New England Journal of Medicine report the annualized attack rate among the 89 AIP patients was 3.2 versus 12.5, 74% lower, with lower urinary ALA and PBG, fewer hemin days and better daily pain scores, alongside more liver and kidney adverse events and injection site reactions[4].
All but 1 patient (93) entered an open-label extension of up to 30 months. In the 36-month final analysis the median annualized attack rate on givosiran was 0.4, and at the end of the extension 86% of the continuous givosiran group and 92% of the placebo crossover group had no attacks, with hemin use near zero in most patients[5]. The FDA approved Givlaari on November 20, 2019 with Breakthrough Therapy, Priority Review and Orphan Drug designations[2][3].
Development history
Alnylam began the Phase 1 study of ALN-AS1 in patients with AIP in 2015 (NCT02452372) and a Phase 1/2 long-term study in 2016 (NCT02949830), then started ENVISION in November 2017[6]. The FDA approved Givlaari on November 20, 2019 for adults with acute hepatic porphyria, calling it the first treatment for the disease and noting the 70% drop in attacks[2].
It was Alnylam's second approved RNA interference medicine, after Onpattro in 2018. Drugs@FDA lists labeling supplements approved in 2021, 2023 and 2024, and the current label, dated September 2025, carries warnings for raised homocysteine (seen in the extension study) and pancreatitis (reported after approval) that were not part of the original trial findings[3][1].
Alnylam also runs ELEVATE (NCT04883905), a registry of people with AHP that follows patients whether or not they take Givlaari, recruiting through 2030[7].
Explore Acute Hepatic Porphyria trials
Other Acute Hepatic Porphyria treatments
Common questions about Givosiran
▸What is Givosiran (Givlaari)?
The only FDA-approved medicine that prevents acute hepatic porphyria attacks rather than treating them once they start. A once-monthly injection under the skin for adults, given by a healthcare professional, that silences the liver gene behind the toxic buildup.
▸How does Givosiran work?
In every acute hepatic porphyria the liver's first heme-making enzyme, ALAS1, runs too fast whenever something pushes the liver to make more heme, and the early building blocks aminolevulinic acid (ALA) and porphobilinogen (PBG) pile up and poison nerves[1]. Givosiran is a short double strand of RNA attached to a sugar (GalNAc) that liver cells pull inside. Once there, it tells the cell's own RNA interference machinery to destroy the messenger RNA for ALAS1, so the cell makes much less of the enzyme and ALA and PBG fall[1]. One dose keeps working for about a month, which is why it is given monthly. The label describes the effect as reducing the elevated liver ALAS1 mRNA and lowering circulating ALA and PBG, the factors associated with attacks and other disease manifestations of AHP[1].
▸What are the side effects of Givosiran?
The label has no boxed warning but 6 warnings. Anaphylaxis occurred in under 1% of trial patients, so it must be given where medical support is available[1]. Liver enzyme (ALT) rises of at least 3 times the upper limit of normal occurred in 15% of patients in the placebo-controlled trial, mostly between months 3 and 5; liver tests are checked before starting, monthly for the first 6 months and then as needed, and the dose can be halved to 1.25 mg/kg after a rise settles[1]. Kidney effects (a rise in creatinine or a fall in eGFR) were reported in 15% of the givosiran group, with a median creatinine rise of 0.07 mg/dL at month 3, and kidney function is monitored during treatment[1]. Injection site reactions, redness, pain, itching, rash, discoloration or swelling, affected 25% and were mild in 11 of 12 people who had them; 1 person had a brief recall reaction at an earlier site[1]. Blood homocysteine rose in 16% of patients during the open-label extension; the label asks for a baseline level and, if it is high, checking folate, B12 and B6 and considering a B6 supplement[1]. Acute pancreatitis, some cases severe, has been reported since approval, so new upper abdominal pain on Givlaari should not be assumed to be a porphyria attack[1]. In the 6-month placebo-controlled part of ENVISION the most common reactions were nausea (27% vs 11% on placebo) and injection site reactions (25% vs 0%), followed by rash (17% vs 4%), creatinine increase (15% vs 4%), transaminase elevations (13% vs 2%) and fatigue (10% vs 4%); 1 patient stopped permanently for raised liver enzymes[1]. Givosiran also raises blood levels of medicines cleared by CYP1A2 and CYP2D6, so some drugs may need a lower dose[1].
▸How is Givosiran taken?
Givlaari is injected under the skin once a month by a healthcare professional; it is not approved for self-injection[1]. The dose is 2.5 mg/kg of actual body weight, drawn from a single-dose vial that holds 189 mg in 1 mL, so most adults need less than 1 vial per dose and anyone needing more than 1.5 mL gets the dose split between 2 syringes and 2 sites at least 2 cm apart[1]. Sites are the abdomen (avoiding a 5 cm circle around the navel), the back or side of the upper arms, or the thighs, rotated each month[1]. A missed dose is given as soon as possible and the monthly schedule restarts from that day[1]. If liver enzymes rise sharply and then improve after a pause, the dose is restarted at 1.25 mg/kg and can go back to 2.5 mg/kg if the enzymes stay settled[1]. Vials are stored at 2 to 25 C (36 to 77 F) in the carton and need no mixing or dilution[1]. Alnylam keeps a treatment center directory on Givlaari.com for finding a site that gives the injections[9].
▸Is Givosiran FDA approved?
Yes, Givosiran (Givlaari) is FDA approved (2019) for the treatment of Acute Hepatic Porphyria.
▸Does Givlaari treat a porphyria attack or prevent one?
It prevents attacks. Givlaari is a monthly injection that lowers the liver's output of ALA and PBG over time; in its trial it cut the rate of attacks by 70%. An attack that has already started is still treated in the hospital with IV hemin (Panhematin), glucose, fluids and pain control. Trial patients kept using hemin for breakthrough attacks, and they needed it far less often.
▸Who can take Givlaari?
Adults with acute hepatic porphyria, which includes AIP, HCP, VP and ADP. The pivotal trial enrolled people who had at least 2 attacks in the previous 6 months, so it is intended for people with recurrent attacks. It is not approved for children, and people who have never had an attack are not candidates.
▸What blood tests are needed on Givlaari?
Liver enzymes before the first dose, every month for the first 6 months and then as your doctor decides, because 15% of trial patients had ALT rise to 3 times normal, mostly in months 3 to 5. Kidney function is checked during treatment, and blood homocysteine is measured before starting and watched afterward; a high level may call for a vitamin B6 supplement.
▸How is Givlaari given and can I inject it myself?
A healthcare professional injects it under the skin once a month at a dose of 2.5 mg/kg of body weight. The label limits it to professional use because anaphylaxis, though rare, has occurred. Alnylam's treatment center directory on Givlaari.com lists sites.
▸What are the most common side effects of Givlaari?
In the 6-month placebo-controlled trial: nausea (27%), injection site reactions (25%), rash (17%), a rise in creatinine (15%), raised liver enzymes (13%) and fatigue (10%). Since approval, acute pancreatitis has been reported, some cases severe, so new upper abdominal pain should be checked rather than assumed to be porphyria.
▸What help is there with the cost of Givlaari?
Alnylam Assist (1-833-256-2748) enrolls patients once a doctor submits a Start Form. It offers a copay program for eligible people with commercial insurance (not government plans), help during coverage delays, referrals to independent foundations, and a Patient Assistance Program that provides the drug at no cost to eligible patients, primarily those who are uninsured.
Sources and references
Every factual claim on this page is drawn from the public sources listed below. Click any reference to open the original document.
- Alnylam Pharmaceuticals via openFDA · 2025-09-10. GIVLAARI (givosiran) injection, prescribing information (openFDA, set_id 167e663c-11e1-497b-a3fc-951d65d58eaa, version 14). https://api.fda.gov/drug/label.json?search=set_id:%22167e663c-11e1-497b-a3fc-951d65d58eaa%22
- U.S. Food and Drug Administration · 2019-11-20. FDA approves first treatment for inherited rare disease. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-inherited-rare-disease
- U.S. Food and Drug Administration (openFDA) · 2026-10-18. Drugs@FDA record for NDA212194 (original approval November 20, 2019; labeling supplements 2021, 2023, 2024). https://api.fda.gov/drug/drugsfda.json?search=application_number:%22NDA212194%22
- New England Journal of Medicine · 2020-06-11. Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria. https://pubmed.ncbi.nlm.nih.gov/32521132/
- Journal of Hepatology · 2023-11. Efficacy and safety of givosiran for acute hepatic porphyria: Final results of the randomized phase III ENVISION trial. https://pubmed.ncbi.nlm.nih.gov/37479139/
- ClinicalTrials.gov. ENVISION: A Study to Evaluate the Efficacy and Safety of Givosiran (ALN-AS1) in Patients With Acute Hepatic Porphyrias. https://clinicaltrials.gov/study/NCT03338816
- ClinicalTrials.gov. ELEVATE, a Registry of Patients With Acute Hepatic Porphyria (AHP). https://clinicaltrials.gov/study/NCT04883905
- Alnylam Pharmaceuticals · 2026-10-18. Financial Assistance, GIVLAARI (givosiran), Alnylam Assist. https://www.alnylamassist.com/givlaari/financial-assistance
- Alnylam Pharmaceuticals · 2026-10-18. GIVLAARI (givosiran) patient site: resources and treatment center directory. https://www.givlaari.com/resources