The US Food and Drug Administration (FDA) has designated NTLA-2002 for the treatment of hereditary angioedema as a Regenerative Medicine Advanced Treatment (RMAT), according to Intellia Therapeutics, Inc., a leading clinical-stage genome editing business (HAE). NTLA-2002 is a CRISPR-based in vivo experimental therapy intended to inactivate the target gene, kallikrein B1 (KLKB1), in order to perhaps stop HAE patients from experiencing potentially fatal swelling attacks.
“The RMAT classification is significant validation of our preliminary clinical findings. According to John Leonard, M.D., president and chief executive officer of Intellia, “It suggests that a single dose of NTLA-2002 has the potential to address severe unmet medical needs for persons with hereditary angioedema. In order to expedite the development of NTLA-2002, an experimental in vivo CRISPR-based therapeutic, and to provide patients with a potentially game-changing treatment more swiftly, we look forward to continue our fruitful engagement with the FDA.
In order to speed up the development and review of potential therapeutic candidates, including genetic therapies, intended to treat, alter, reverse, or cure a serious or life-threatening condition, the 21st Century Cures Act created the RMAT designation. Benefits of RMAT classification include possible priority evaluation of a product’s biologics licence application, early interactions with the FDA, including talks on surrogate or intermediate endpoints that may support rapid approval and satisfy post-approval criteria (BLA). The RMAT is Intellia’s third special regulatory designation for the NTLA-2002. Also, the FDA designated NTLA-2002 as an orphan drug, and the U.K. Medicines and Healthcare products Regulatory Agency awarded it the Innovation Passport designation.
Adults with Type I or Type II hereditary angioedema are participating in Intellia’s multi-national phase 1/2 trial to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of NTLA-2002 (HAE). This includes calculating the plasma levels of kallikrein protein and activity as well as the frequency of HAE attacks. In the open-label, single-ascending dosage phase 1 of the trial, two dose levels of NTLA-2002 were identified for further examination in the phase 2 randomised, placebo-controlled phase. This phase 1/2 trial will determine the NTLA-2002 dose to be used in further investigations. In 2022, Intellia released encouraging preliminary findings from the Phase 1 study showing significant, dose-dependent decreases in plasma kallikrein and substantial decreases in patient HAE attacks. Patient screening for the study’s phase 2 is still going on.
NTLA-2002 is the first single-dose investigational drug being tested in clinical trials with the potential to continually lower kallikrein activity and prevent attacks in persons with hereditary angioedema. It is based on the Nobel Prize-winning CRISPR/Cas9 technology (HAE). The kallikrein B1 (KLKB1) gene, which codes for prekallikrein, the kallikrein precursor protein, is intended to be inactivated by NTLA-2002, an investigational CRISPR treatment candidate owned entirely by the company. NTLA-2002 is Intellia’s second CRISPR therapeutic candidate under research and will be infused intravenously to modify disease-causing genes within the human body in a single dose. A two-part genome editing system, including messenger RNA that encodes the Cas9 enzyme and guide RNA specific to the disease-causing gene, is delivered to the liver using lipid nanoparticles via Intellia’s patented non-viral platform. Both components work together to perform precision editing.
A rare genetic illness known as hereditary angioedema (HAE) causes severe, sporadic, inflammatory assaults in a variety of body organs and tissues. These attacks can be excruciatingly painful, incapacitating, and even fatal. One in 50,000 persons are thought to be afflicted by HAE, and current medications frequently involve lifelong regimens that may require chronic intravenous (IV), subcutaneous (SC), or daily oral dosing to maintain ongoing pathway suppression for disease control. Despite persistent management, breakthrough attacks still happen. The prevention of HAE attacks can be managed with the help of the clinically proven method of kallikrein inhibition. Using CRISPR/Cas9 technology, Intellia Therapeutics, a top clinical-stage genome editing business, is creating innovative treatments with the potential to be curative.