Alnylam's release of long-term data on Givlaari's treatment of AHP is expected to dispel safety questions.

In November 2019, Alnylam's Givlaari was approved for sale as the world's second RNAi drug and the first to treat acute hepatic disease (AHP) in adults.
when Givlaari was approved, some observers expressed concern about the short duration of clinical trials and questionable safety concerns.
but eight months after the launch, Alnylam has released long-term, open-label extension data that promises to dispel concerns about the safety of long-term drug use.based on open label extension data from the Phase III ENVISION study, released June 30, Givlaari showed consistent efficacy in reducing the number of seizures in AHP patients over a one-year period of treatment, and there was evidence that the efficacy increased over time.
12-month data also reinforces the six-month double-blind period in the New England Journal of Medicine (NEJM), published in June, which showed that Givlaari was significantly better than placebo in reducing seizures in patients.
the largest-ever interventional study for ENVISIONAHP, involving 94 patients at 36 research centers in 18 countries, to assess the efficacy and safety of Givlaari and placebo treatment for AHP.
study, patients were randomly assigned to Givlaari (2.5 mg/kg per month) or a placebo at a 1:1 ratio.
six-month double-blind period data showed that Givlaari reached the main endpoint: compared to placebo, Givlaari reduced the annualization rate (AAR) of compound radon (a seizure requiring hospitalization, emergency consultation, or intravenous administration at home) by 74% and the median AAR by 1.0 times.
study period, Givlaari showed acceptable safety and tolerance.
after completing 6 months of double-blind treatment, all eligible patients (93 out of 94 cases, 99%) entered the group for an open label extension period.
in this study, some patients were initially studied at a dose of 1.25 mg/kg to produce additional data at lower dose levels, and because there is evidence that efficacy may be improved at higher doses, all patients entering the open label extension phase are now transitioning to a dose level of 2.5 mg/kg.
12-month results showed that the AAR continued to decrease and the median AAR was 0.0 for patients who continued to receive Givlaari during the open label extension period.
the proportion of patients treated with Givlaari for seizure-free cases, with a double blindness period of 50.0 per cent and an increase of 61.7 per cent in the first 6 months of the open label expansion period. in addition,
patients who continued to receive Givlaari treatment during the open label expansion period, continued reduction of amino acetylacid and bile pigment, continued reduction in hemoglobin use, decreased daily levels of severe pain reported by patients, and continued improvement in patient quality of life and functional capacity reported.
patients who received Givlaari during the transition from a placebo in double-blind to an open label extension, a 76 percent reduction in AAR, similar to the aAR reduction experienced by patients treated with Givlaari in double-blind period.
in addition, patients who transitioned from placebo to Givlaari had reduced hererin use during the open label extension period and a decrease in reported daily worst pain levels, consistent with the decrease in Givlasa treatment patients observed during the double-blind period.

the security during the open label expansion period is consistent with the double blind period, and no new security discoveries are found.
as of July 23, 2019, the most common adverse events (AE) associated with Givlaari include injection site reactions, nausea and fatigue.
severe adverse events included 2 cases of chronic kidney disease during double blindness and urinary tract infections in 2 patients during the open label extension period.
combined double-blind period and open label expansion period, liver and kidney AE were 16 cases (17%) and 10 (11%) respectively.
the severity of most adverse events was mild or moderate, no new adverse events were caused by drug suspension and no deaths occurred during the open label extension period.
AHP is an extremely rare genetic disorder caused by a genetic defect that causes the liver to lack certain enzymes needed to produce hemoglobin, which causes radon to accumulate in the body to the amount of poisoning.
the disease is characterized by unexplained abdominal pain, frequently disabling episodes, and chronic symptoms that can greatly affect the patient's daily function.
AHP can be life-threatening due to the possibility of paralysis and respiratory arrest during the attack.

. Givlaari is a drug that targets the root causes of AHP disease by reducing the mRNA of aminoacetic acid synthase 1 (ALAS1) through RNAi, thereby reducing toxins associated with AHP attacks and other disease manifestations.
data from the ENVISION open label extension period are very encouraging, showing that Givlaari treatment continues to reduce AAR and continuously improve patient health, daily function and quality of life in secondary and exploratory terms.
currently, four late-stage RNAi compounds in the Alnylam pipeline, including two co-operative drugs, will face FDA review decisions over the next 6-18 months, which will significantly expand the company's ipo portfolio from two to six.
, cholesterol-lowering PCSK9 target drug inclisiran uses Alnylam's proprietary ESC-GalNAc conjugate technology, and The Medicines Company (TMC) has acquired global development rights through a licensing agreement.

Novartis's $9.4 billion acquisition of TMC in November 2019 will bring in the drug, which is under review in the United States and the European Union and has the potential to become the first cholesterol-lowering RNAi drug.
based on the strong cholesterol-lowering efficacy in clinical programs and the huge advantage of only 2 subcutaneous injections per year, the drug has a very good market penetration opportunity.
Source: 1, Alnylam's RNAi the Girapy ari show lasting effect one life into treatment, new data show 2, Alnylam Reports New 12-Interim Interim Data From the Phase 3 Gevosiran in Siomh Porphyria.