Onpattro vs Tegsedi - how do they compare?

Both Onpattro and Tegsedi are used to slow or prevent the progression of hATTR by reducing levels of TTR, a protein in the body. Even though they work in different ways, they are both effective at reducing TTR and improving nerve-related symptoms and function.

Onpattro is given once every three weeks by a health professional and Tegsedi can be self-administered, once weekly. Both are expensive, around $30,000 every three weeks, and both may cause allergic-type reactions and vitamin A deficiency.

Because Tegsedi carries a black box warning for thrombocytopenia (low platelet counts) and kidney damage, it requires ongoing monitoring and is only available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS). Onpattro does not require ongoing monitoring but needs to be administered by a health care professional.

How are Onpattro and Tegsedi similar?

Both Onpattro and Tegsedi are approved for use in people with hereditary transthyretin (TTR)-mediated amyloidosis (hATTR) which is a rare condition caused by abnormal deposits of TTR, a protein that is present in all human serum. A build-up of TTR interferes with nerve and organ function and can cause death if left untreated.

• Both Onpattro and Tegsedi decrease levels of TTR, delaying, or preventing disease progression.
• Both Onpattro and Tegsedi have been shown in clinical trials to improve symptoms of nerve damage and improve nerve function.
• There have been no trials comparing Onpattro to Tegsedi directly.

What are the differences between Onpattro and Tegsedi?

Although both Onpattro and Tegsedi can be used to treat hATTR, there are some differences between them.

Firstly, Onpattro is the brand name for the generic drug, patisiran, and Tegsedi is the brand name for the generic drug, inotersen.

Onpattro has a different way of working than Tegsedi, although both are effective at reducing levels of TTR in the body.

• Onpattro contains small lipid nanoparticles that contain small interfering RNAs that decrease TTR by breaking down mutated or wild-type genetic material that codes for TTR.
• Tegsedi is a chemically modified RNA molecule that binds to the messenger RNA that codes for TTR. This leads to a breakdown of TTR by RNAase.

There are differences in the way they are administered.

• Onpattro is given by a slow intravenous infusion once every three weeks. All patients need to receive premedication consisting of an intravenous corticosteroid, oral acetaminophen, and intravenous H1 and H2 blockers at least 60 minutes before the start of the infusion. Onpattro needs to be given by a health professional.
• Tegsedi is given by subcutaneous injection (an injection under the skin), once a week. People can be taught how to self-administer Tegsedi.

Which has more side effects? Onpattro or Tegsedi?

Side effects of Onpattro and Tegsedi also differ.

• Common side effects of Onpattro include upper respiratory tract infections, dyspepsia, shortness of breath, muscle spasms, joint pain, a rash, vertigo, and rarely, heart block.
• Common side effects of Tegsedi include nausea, headache, tiredness, low platelet counts (thrombocytopenia), and fever. Tegsedi may also cause inflammatory and immune system problems (such as walking, weakness, and spasms in legs, back pain, weight loss, headache, vomiting, and problems with speech), liver effects, and rarely, stroke.
• Side effects that are common to both Onpattro and Tegsedi include injection site reactions (such as redness or pain at the injection site), allergic reactions, and eye problems, because both lead to a decrease in vitamin A.

Supplements of vitamin A should be considered and people who develop vision problems (such as night blindness) suggestive of vitamin A deficiency after taking either Onpattro or Tegsedi should be referred to an ophthalmologist.

Because Tegsedi carries a black box warning for thrombocytopenia (low platelet counts) and kidney damage, and requires frequent monitoring it is only available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS) called the Tegsedi REMS Program.

Onpattro is available through a health professional and ongoing laboratory monitoring is not required.

How does the dosage of Onpattro and Tegsedi differ?

Onpattro and Tegsedi differ in their recommended dose.

• The recommended dose of Onpattro is 0.3mg/kg once every 3 weeks for patients weighing less than 100kg. For patients weighing over 100kg, the recommended dosage is 30mg once every three weeks.
• The recommended dose of Tegsedi is 284mg injected subcutaneously, once a week.

Which is more expensive? Onpattro or Tegsedi?

Both Onpattro and Tegsedi are expensive.

• Onpattro costs approximately $9,927 for a 5ml intravenous solution that contains Onpattro 2mg/ml. A 30mg dose of Onpattro costs $29,781.
• Tegsedi costs $9032 for one 1.5mL subcutaneous injection that contains 284mg of Tegsedi.

Because Onpattro is given once every three weeks and Tegsedi is given once weekly, costs end up similar.