25 March 2020 - - Swiss RNAi therapeutics company Alnylam Pharmaceuticals, Inc. (NASDAQ: ALNY) and Turkey-based Gen, a GMP-certified pharmaceutical company specialising in rare diseases, have inked an exclusive Distribution Agreement for Onpattro, a first-in-class RNAi therapeutic for the treatment of hATTR amyloidosis in adults with Stage 1 or Stage 2 polyneuropathy.

Patients in Turkey were among those who participated in the randomized, double-blind, placebo-controlled, global Phase 3 APOLLO study, the largest-ever study in hATTR amyloidosis patients with polyneuropathy, which led to the approval of Onpattro in the US and EU in 2018.

Onpattro is an RNAi therapeutic that was approved in the United States and Canada for the treatment of the polyneuropathy of hATTR amyloidosis in adults.

Onpattro is also approved in the European Union, Switzerland and Brazil for the treatment of hATTR amyloidosis in adults with Stage 1 or Stage 2 polyneuropathy, and in Japan for the treatment of hATTR amyloidosis with polyneuropathy.

Based on Nobel Prize-winning science, Onpattro is an intravenously administered RNAi therapeutic targeting transthyretin.

It is designed to target and silence TTR messenger RNA, thereby blocking the production of TTR protein before it is made.

Onpattro blocks the production of TTR in the liver, reducing its accumulation in the body's tissues in order Onpattro halt or slow down the progression of the polyneuropathy associated with the disease.

Infusion-related reactions have been observed in patients treated with patisiran.

In a controlled clinical study, 19% of patisiran-treated patients experienced IRRs, compared to 9% of placebo-treated patients.

The most common symptoms of IRRs with patisiran were flushing, back pain, nausea, abdominal pain, dyspnoea, and headache.

Hypotension, which may include syncope, has also been reported as a symptom of IRRs.

To reduce the risk of IRRs, patients should receive premedication with a corticosteroid, paracetamol, and antihistamines (H1 and H2 blockers) at least 60 minutes prior to patisiran infusion. Monitor patients during the infusion for signs and symptoms of IRRs.

If an IRR occurs, consider slowing or interrupting the infusion and instituting medical management as clinically indicated. If the infusion is interrupted, consider resuming at a slower infusion rate only if symptoms have resolved.

In the case of a serious or life-threatening IRR, the infusion should be discontinued and not resumed.

Patisiran treatment leads to a decrease in serum vitamin A levels. Patients receiving patisiran should take oral supplementation of approximately 2500 IU vitamin A per day to reduce the potential risk of ocular toxicity due to vitamin A deficiency.

Doses higher than 2500 IU vitamin A per day should not be given to try to achieve normal serum vitamin A levels during treatment with patisiran, as serum levels do not reflect the total vitamin A in the body.

Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g. including reduced night vision or night blindness, persistent dry eyes, eye inflammation, corneal inflammation or ulceration, corneal thickening or corneal perforation).

The most common adverse reactions that occurred in patients treated with patisiran were peripheral oedema and infusion-related reactions.

RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development.

Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine.

By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality.

Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of current medicines by potently silencing messenger RNA the genetic precursors that encode for disease-causing proteins, thus preventing them from being made.

This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.