Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Givosiran · 4 trials · 9 indications
Porphyria attacks were defined as meeting all of the following criteria: an acute episode of neurovisceral pain in the abdomen, back, chest, extremities and/or limbs, no other medically determined cause, and required treatment with intravenous (IV) dextrose or hemin, carbohydrates, or analgesics, or other medications such as antiemetics at a dose or frequency beyond the participant's usual daily porphyria management. The annualized rate of porphyria attacks is a composite endpoint which included porphyria attacks requiring hospitalization, urgent healthcare visit, or IV hemin administration at home.
Area under the concentration-time curve (AUC)
An AE is any untoward medical occurrence in a participant or clinical investigational patient administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
| Arm | Type | Description |
|---|---|---|
| Givosiran/Givosiran | EXPERIMENTAL | Givosiran 2.5 mg/kg administered subcutaneously (SC), monthly (QM), for 6 months during the 6-Month Double-blind (DB) Period, followed by givosiran 2.5 mg/kg or 1.25 mg/kg SC, QM for 29 months during the Open-label Extension (OLE) Period. |
| Placebo/Givosiran | PLACEBO_COMPARATOR | Matching placebo (normal saline \[0.9% NaCl\]) was administered SC, QM, for 6 months during the 6-Month DB Period, followed by givosiran 2.5 mg/kg or 1.25 mg/kg SC, QM for 29 months during the OLE period. |
| Givosiran with 5-probe cocktail | EXPERIMENTAL | - |
| Givosiran | EXPERIMENTAL | At the beginning of this study, participants received either givosiran 2.5 mg/kg subcutaneous (SC) injection once monthly(QM), givosiran 5.0 mg/kg SC injection QM, or givosiran 5.0 mg/kg SC injection once every 3 months (Q3M). Within a year, all participants were transitioned to givosiran 2.5 mg/kg SC injection QM. |
| givosiran (ALN-AS1) | ACTIVE_COMPARATOR | - |
| Sterile Normal Saline (0.9% NaCl) | PLACEBO_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| Givosiran | DRUG | Givosiran by SC |
| Placebo | DRUG | Matching placebo (normal saline \[0.9% NaCl\]) by SC |
| 5-probe cocktail | DRUG | includes midazolam, caffeine, losartan, omeprazole, and dextromethorphan |
| givosiran (ALN-AS1) | DRUG | Single or multiple doses of ALN-AS1 by subcutaneous (sc) injection |
| Sterile Normal Saline (0.9% NaCl) | DRUG | calculated volume to match active comparator |
Inclusion Criteria: * ≥ 12 years of age * Diagnosed with Acute Hepatic Porphyria (Acute Intermittent Porphyria, Hereditary Corproporhyria, Variegate Porphyria, aminolevulinic acid (ALA) dehydratase deficient porphyria) * Elevated urinary or plasma porphobilinogen (PBG) or ALA values within the past...
Givosiran is an investigational small molecule being developed for the treatment of acute hepatic porphyria, including acute intermittent porphyria. It is designed to address the underlying enzyme deficiency that leads to the accumulation of toxic precursors in the liver, which cause the symptoms of these rare genetic disorders.
Givosiran targets aminolevulinate synthase 1 (ALAS1), an enzyme involved in heme biosynthesis. By reducing ALAS1 activity, givosiran aims to lower the levels of porphobilinogen and aminolevulinic acid, which are precursors that accumulate and trigger acute porphyria attacks.
Givosiran is being developed by Alnylam Pharmaceuticals, Inc., a biopharmaceutical company focused on RNA interference therapeutics. Alnylam is publicly traded on the Nasdaq under the ticker symbol ALNY.
Givosiran is in Phase 3 clinical development for acute hepatic porphyria. It has completed Phase 1 and Phase 3 trials, including the ENVISION study, which evaluated its efficacy and safety in patients with acute hepatic porphyrias. It remains investigational and has not yet been approved by regulatory authorities.
Givosiran has been studied in several clinical trials, including NCT02452372, a Phase 1 study in patients with acute intermittent porphyria; NCT02949830, a long-term safety study; NCT03338816, the Phase 3 ENVISION trial in acute hepatic porphyrias; and NCT03505853, a drug interaction study. All trials listed are completed.
Yes, Givosiran is also known as ALN-AS1. In clinical trial records, it is referred to by both names. For example, the Phase 1 study NCT02452372 is titled 'A Phase 1 Study of Givosiran (ALN-AS1) in Patients With Acute Intermittent Porphyria (AIP).'