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About AHP

Acute hepatic porphyria (AHP) is a rare genetic disease characterized by debilitating, potentially life-threatening attacks1,2

There are 4 types of AHP1,3

Most common
Chart showing the 4 types of AHP ranging from most to least common
Extremely rare
  • Acute Intermittent Porphyria (AIP)~80% of all AHP cases are AIP1
  • Variegate Porphyria (VP)
  • Hereditary Coproporphyria (HCP)
  • ALAD-Deficiency Porphyria (ADP)

ALAD=delta-aminolevulinic acid dehydratase.

AHP attacks can be severe, unpredictable, and progressive1

  • AHP can affect anyone, but is most commonly seen in women of childbearing age3
  • Attacks generally last 3 to 7 days, but recovery can take longer1
  • Severe attacks can progress to respiratory failure or paralysis, leading to temporary or permanent disability2,4
  • In one study, patients with recurrent attacks averaged 5 hospitalizations in a 12-month period5*
  • Some patients with AHP may develop long-term complications, such as chronic kidney disease (CKD), hepatocellular carcinoma (HCC), and hypertension4

*Results from EXPLORE, a 12-month prospective natural history study of 112 patients who experienced recurrent AHP attacks (≥3 attacks/year) or received prophylactic treatment. Attacks were defined as those requiring increased pain medication or carbohydrate intake, hemin administration, and/or hospitalization for signs and symptoms of AHP.5

"The first thing I think when I hear porphyria is, debilitating." —Lina, an Alnylam Patient Ambassador

Explore a Study in Patients With AHP

Common signs and symptoms of an AHP attack2,6,7†

SEVERE, DIFFUSE ABDOMINAL PAIN6,7

Plus icon
1 or more of the following

AUTONOMIC
Nervous System6,7

  • Nausea/Vomiting
  • Constipation
  • Tachycardia
  • Systemic arterial hypertension

CENTRAL
Nervous System2,6,7

  • Seizures
  • Anxiety
  • Mental status changes

CUTANEOUS7

  • Skin lesions on
    sun-exposed areas (Cutaneous symptoms primarily occur in HCP and VP.)

PERIPHERAL
Nervous System6,7

  • Limb weakness
    or pain
  • Peripheral neuropathy

OTHER
Common AHP Symptoms7,8

  • Hyponatremia
  • Dark, reddish urine

Image of a body clutching its highlighted abdomen

Image of a body clutching its highlighted abdomen

†These are not all the possible signs and symptoms of an AHP attack.

AHP=acute hepatic porphyria; HCP=hereditary coproporphyria; VP=variegate porphyria.

>90% of patients report abdominal pain during AHP attacks6

AHP can go undiagnosed for many years3,11

Because of overlapping symptoms, patients with AHP are often misdiagnosed with other diseases such as6,9,10:

Intestines icon

Gastrointestinal disorders

  • Acute gastroenteritis
  • with vomiting
  • Irritable bowel syndrome (IBS)
  • Hepatitis

Gynecological disorder icon

Gynecological disorder

  • Endometriosis

Brain icon

Neurological/​neuropsychiatric disorders

  • Fibromyalgia
  • Guillain-Barré syndrome
  • Psychosis

Scalpel icon

Acute abdomen conditions

  • Appendicitis
  • Cholecystitis
  • Peritonitis
  • Pancreatitis
  • Intestinal occlusion

Explore the journeys of real AHP patients on GIVLAARI

Every patient with AHP has a unique story to tell. Discover the journeys to diagnosis and beyond for 3 real patients with AHP.

See Their Stories
NEXT: How GIVLAARI® (givosiran) Works

References: 1. Simon A, Pompilus F, Querbes W, et al. Patient. 2018;11:527-537. 2. Puy H, Gouya L, Deybach JC. Lancet. 2010;375:924-937. 3. Bissell DM, Anderson KE, Bonkovsky HL. N Engl J Med. 2017;377:862-872. 4. Neeleman RA, Wagenmakers MAEM, Koole-Lesuis RH, et al. J Inherit Metab Dis. 2018;41:809-817. 5. Gouya L, Ventura P, Balwani M, et al. Hepatology. 2020;71(5):1546-1558. 6. Ventura P, Cappellini MD, Biolcati G, Guida CC, Rocchi E; Gruppo Italiano Porfiria (GrIP). Eur J Intern Med. 2014;25:497-505. 7. Anderson KE, Bloomer JR, Bonkovsky HL, et al. Ann Intern Med. 2005;142:439-450. 8. Balwani M, Wang B, Anderson KE, et al; Porphyrias Consortium of the Rare Diseases Clinical Research Network. Hepatology. 2017;66:1314-1322. 9. Ko JJ, Murray S, Merkel M, et al. Poster presented at: American College of Gastroenterology Annual Scientific Meeting; October 5-10, 2018; Philadelphia, PA. 10. Alfadhel M, Saleh N, Alenazi H, Baffoe-Bonnie H. Neuropsychiatr Dis Treat. 2014;10:2135-2137. 11. Anderson KE. Mol Genet Metab. 2019;128:219-227.   
 

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.

Blood Homocysteine Increased

Increases in blood homocysteine levels have occurred in patients receiving GIVLAARI. In the ENVISION study, during the open label extension, adverse reactions of blood homocysteine increased were reported in 15 of 93 (16%) patients treated with GIVLAARI. Measure blood homocysteine levels prior to initiating treatment and monitor for changes during treatment with GIVLAARI. In patients with elevated blood homocysteine levels, assess folate, vitamins B12 and B6. Consider treatment with a supplement containing vitamin B6 (as monotherapy or a multivitamin preparation).

Pancreatitis

Cases of acute pancreatitis, some severe, have been reported in patients receiving GIVLAARI. To ensure appropriate management, consider acute pancreatitis as a potential diagnosis in patients with signs/symptoms of acute pancreatitis. Consider interruption and/or discontinuation of GIVLAARI treatment for severe cases.

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.