Takeda Drug Wins First FDA Approval in Rare, Inherited Blood Clotting Disorder

A Takeda Pharmaceutical drug is now the first FDA-approved therapy for a rare, inherited enzyme deficiency that leads to blood clotting problems and a cascade of complications, some of them potentially fatal.

The disease, congenital thrombotic thrombocytopenic purpura (cTTP), stems from a mutation in the gene that codes for ADAMTS13, an enzyme that regulates blood clotting. Without enough of this enzyme, blood clots form in small blood vessels throughout the body. Those clots lead to severe bleeding episodes, strokes, and organ damage. This rare disease is estimated to affect fewer than 1,000 people in the U.S., according to the FDA.

Current cTTP treatment involves prophylactic plasma-based therapy, which replenishes deficient ADAMTS13 with the goal of reducing the risk of clotting and bleeding problems. New Takeda drug Adzynma is an engineered version of the key enzyme. The intravenously infused therapy is administered every other week. In addition to use as prophylactic therapy, Adzynma is also approved as an on-demand treatment in instances of an acute event.

Adzynma was studied in an open-label crossover Phase 3 study. Patients were randomly assigned to a group treated with either the study drug or plasma-based therapy. After six months, each group crossed over to receive the other treatment. After that second six-month period, all study participants received Adzynma in a six-month continuation period.

Study results showed that no patient experienced an acute clotting event while receiving the Takeda drug. There was one event reported in a patient while receiving plasma-based therapy. No subacute events were reported in patients receiving the study drug during the first two period of the trial, compared to five subacute events in four patients treated with plasma-based therapies. In the continuation period, two patients receiving Adzynma for prophylaxis experienced two subacute events.

The average annualized event rate of thrombocytopenia, or low platelet counts, was 2.0 for those receiving Adzynma and 4.44 in those receiving plasma-based therapies. The FDA said that while the clinical significance of this comparison is unknown, thrombocytopenia is a manifestation of TTP and is an important biological indicator of disease activity. In further tests of the drug’s distribution throughout the body, results showed patients treated with the Takeda drug achieved a four- to-five-fold increase in ADAMTS13 activity after a single infusion compared to those treated with plasma-based therapies.

On measures of safety, Adzynma was comparable to plasma-based therapies. The most common adverse reactions in the trial included headache, diarrhea, migraine, abdominal pain, and nausea. No patients treated with the Takeda drug developed neutralizing antibodies that could render the therapy ineffective.

Takeda won another FDA approval this past week. The agency greenlit fruquintinib, brand name Fruzaqla, a targeted therapy for metastatic colorectal cancer. Fruzaqla is a small molecule designed to block three vascular endothelial growth factors (VEGF), proteins that play a role in the formation of blood vessels that support tumor growth. The FDA nod covers the treatment of colorectal cancer in adults who previously received chemotherapy, an anti-VEGF therapy, and if medically appropriate, a therapy that blocks a different target called epidermal growth factor receptors.

Takeda acquired Fruzaqla early this year, paying Hutchmed $400 million up front. Tokyo-based Takeda gained global rights to the small molecule, excluding certain regions in Asia where Hong Kong-based Hutchmed retains rights. The drug has been approved for use in China since 2018. Hutchmed is eligible for up to $730 million in milestone payments, plus royalties from sales.

Several other high-profile products won FDA approvals in recent weeks. Here’s a recap of some other notable recent regulatory developments:

—Valneva won accelerated FDA approval for Ixchiq, the first chikungunya vaccine. Chikungunya is a mosquito-borne virus that causes an infection whose symptoms include fever, joint pain, headache, and muscle pain. The Valneva vaccine is made with live, attenuated chikungunya virus and may cause symptoms similar to those of chikungunya infection. The vaccine’s approval comes with a post- marketing requirement for the company to conduct additional tests to assess the risks of severe chikungunya-like adverse reactions.

—Eli Lilly’s diabetes drug Mounjaro won an additional FDA approval for use in chronic weight management. In this new indication, the once-weekly injectable drug will be marketed as Zepbound. Lilly priced the drug at a 20% discount to Wegovy, the Novo Nordisk weight loss drug that addresses the same GLP-1 target and is in hot demand.

—An ACON Laboratories at-home Covid-19 test has received FDA clearance, making it the first over-the-counter antigen test to pass this regulatory bar. The test, called Flowflex, initially received FDA emergency use authorization in 2021. It’s now the second test to complete the traditional FDA premarket review pathway and the first one indicated for use in children younger than 18. In study results reviewed by the FDA, the ACON test correctly identified 89.8% of positive samples and 99.3% of negative samples in individuals who had signs and symptoms of upper respiratory infection.

—The Federal Trade Commission has put 10 biopharma companies on notice for more than 100 patents the antitrust regulator says are improperly listed in the Orange Book, the FDA’s official list of approved products. The FTC says inappropriate Orange Book patent listings enable makers of branded products to delay generic products from reaching the market, which reduces consumer choice and keeps prices high.

—Mirati Therapeutics drug Krazati received approval from United Kingdom regulators for the treatment of adults whose advanced cases of non-small cell lung cancer carries the KRAS G12C mutation. This regulatory decision comes nearly a year after Krazati won accelerated FDA approval for the same indication.

—Amgen won FDA approval for Wezlana, a biosimilar that’s interchangeable with Stelara, a Johnson & Johnson drug with approved uses in multiple inflammatory conditions. In adults, the Wezlana is now approved for treating moderate to severe plaque psoriasis; active psoriatic arthritis; moderately to severely active Crohn’s disease; and moderately to severely active ulcerative colitis. In children age 6 and older, the Amgen biosimilar is approved for treating moderate to severe plaque psoriasis and active psoriatic arthritis.

—Tibsovo, a cancer drug that Servier Pharmaceuticals acquired as part of a $1.8 billion deal, received FDA approval in myelodysplastic syndromes, a group of rare blood cancers. The regulatory nod covers cases of this cancer that have an IDH1 mutation. The drug previously won FDA approvals in acute myeloid leukemia and cholangiocarcinoma.

—Vabysmo, an eye drug from Roche’s Genentech subsidiary, won an additional FDA approval for treating retinal vein occlusion. This condition develops as vein blockage that restricts blood flow in the retina, which leads to vision loss. The regulatory decision marks the third approved indication for the drug, which was previously approved for treating the wet form of age-related macular degeneration and diabetic macular edema.

—Eli Lilly received FDA approval for mirikizumab as a treatment for moderately to severely active ulcerative colitis. The antibody drug, which carries the brand name Omvoh, is engineered to block IL-23, a signaling protein involved in inflammatory pathways. It’s the first approved Lilly treatment for a type of inflammatory bowel disease.

—The FDA approved Santhera Pharmaceuticals’ vamorolone for treating Duchenne muscular dystrophy in children age 2 and older. The drug, which will be marketed as Agamree, is a corticosteroid that provides anti-inflammatory and immunosuppressive effects. The once-daily oral suspension will be marketed in the U.S. by partner Catalyst Pharmaceuticals, which expects a product launch in the first quarter of 2024.

—Enhertu, the HER2-targeting antibody drug conjugate developed by partners Daiichi Sankyo and AstraZeneca, won a new European Union approval as a treatment for advanced cases of non-small cell lung cancer. The EU regulatory decision follows the 2022 FDA approval of Enhertu for this indication. The drug also has EU approvals in breast and gastric cancers.

—Verve Therapeutics received the FDA go-ahead to proceed with a clinical trial testing its gene therapy for heterozygous familial hypercholesterolemia, an inherited form of high cholesterol. The agency had placed a clinical hold on the company’s application last year. The Boston company was able to answer the FDA’s questions by submitting interim clinical data from the dose-escalation portion of the study at sites in the United Kingdom and New Zealand.

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