Here is information on the latest US FDA approvals, the week of November 20 – December 1, 2023
Nirogacestat (Ogsiveo) For Desmoid Tumors
The FDA has approved nirogacestat (Ogsiveo) tablets for adult patients with progressing desmoid tumors who require systemic treatment. Nirogacestat is the first drug to be approved for the treatment of patients with desmoid tumors, a rare subtype of soft tissue sarcomas. Desmoid tumors are non-cancerous but can be locally aggressive and may invade into surrounding structures and organs. Although surgical removal has historically been the treatment of choice, there is a high risk that the tumor will return, or that other health challenges will occur after removal. Nirogacestat works by inhibiting the activity of an enzyme called gamma secretase, which helps activate a signaling protein called Notch. The effectiveness of nirogacestat was evaluated in a randomized trial in 142 adult patients with progressing desmoid tumors not amenable to surgery and showed a significantly improved response rate of 41% in the treatment arm vs 8% in the placebo arm. Nirogacestat was granted Priority Review and also received FDA Fast Track and Breakthrough Therapy designations. Approval was granted to SpringWorks Therapeutics, Inc.
https://springworkstx.com/wp-content/uploads/2023/11/OGSIVEO-US-Prescribing-Information-11.27.23.pdf
Pirtobrutinib (Jaypirca) for CLL/SLL
The FDA has granted accelerated approval of pirtobrutinib (Jaypirca) in adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor. Pirtobrutinib is a third-generation non-covalent, or reversible, BTK inhibitor and is already approved to treat adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor. Pirtobrutinib was approved under the FDA’s Accelerated Approval pathway based on overall response rate (ORR) and duration of response (DOR) from the 1/2 BRUIN trial. According to the written release from the manufacturer Eli Lilly, continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
https://pi.lilly.com/us/jaypirca-uspi.pdf?s=pi
Enfortumab Vedotin (Padcev) With Pembrolizumab (Keytruda) for Urothelial Cancer
The FDA has accepted for priority review a supplemental Biologics License Application (sBLA) for enfortumab vedotin-ejfv (Padcev) in combination with pembrolizumab (Keytruda) for the treatment of adult patients with locally advanced or metastatic urothelial cancer (la/mUC). The FDA is reviewing the application under its Real-Time Oncology Review (RTOR) program, which aims to explore a more efficient review process. If approved, the combination would be the first and only antibody-drug conjugate plus PD-1 inhibitor treatment alternative to chemotherapy in this patient population. The sBLA for first-line use of the combination is based on results from the Phase 3 EV-302 randomized, Phase 3 trial (also known as KEYNOTE-A39) Results of the trial found the combination significantly extended overall survival and progression-free survival compared with standard platinum-containing chemotherapy. The FDA granted the priority review to Astellas Pharma, Inc. and Seagen, Inc. and has set a PDUFA target action date of May 9, 2024.
https://www.prnewswire.com/news-releases/fda-grants-priority-review-for-supplemental-biologics-license-application-sbla-of-padcev-enfortumab-vedotin-ejfv-with-keytruda-pembrolizumab-for-first-line-treatment-of-advanced-bladder-cancer-302002564.html
Lisocabtagene Maraleucel (Breyanzi) for CLL/SLL
The FDA has accepted the supplemental Biologics License Application (sBLA) for lisocabtagene maraleucel (Breyanzi), a CD19-directed CAR T cell therapy. This would expand its current indication to include the treatment of adult patients with relapsed or refractory CLL/SLL who received a prior BTK inhibitor and BCL2 inhibitor. The sBLA of lisocabtagene maraleucel is based on data from the TRANSCEND CLL 004 phase 1/2 study in this patient setting. Lisocabtagene maraleucel is manufactured by Bristol Myers Squib and is under Priority Review.
https://packageinserts.bms.com/pi/pi_breyanzi.pdf
Xanomeline-trospium (KarXT) for Schizophrenia
The FDA has accepted a new drug application for xanomeline-trospium (KarXT) [not to be confused with chimeric antigen receptor (CAR) T-cell therapy]. This is an investigational muscarinic antipsychotic for the treatment of schizophrenia in adults. According to the manufacturer Karuna Therapeutics, the drug acts as a dual M1/M4 muscarinic acetylcholine receptor agonist in the central nervous system and may improve positive, negative and cognitive symptoms of schizophrenia. Unlike current treatments, KarXT does not directly block dopamine receptors. The NDA submission is supported by efficacy and long-term safety results from the EMERGENT program evaluating the drug’s safety and efficacy. KarXT is not associated with common antipsychotic medication side effects like weight gain, somnolence or movement disorders. The application for KarXT has received a PDUFA date of Sept. 26, 2024.
https://investors.karunatx.com/news-releases/news-release-details/karuna-therapeutics-announces-us-food-and-drug-administration
Roflumilast Cream for Atopic Dermatitis
The FDA has accepted a supplemental New Drug Application (sNDA) for roflumilast cream 0.15% for the treatment of atopic dermatitis (AD) in both adults and children as young as 6 years of age. Topical roflumilast cream (also known as ARQ-151) is a small molecule inhibitor of phosphodiesterase-4 (PDE4), which increases the production of proinflammatory mediators and decreases the production of anti-inflammatory mediators. PDE4 has been implicated in a wide range of inflammatory diseases, including psoriasis and chronic obstructive pulmonary disease (COPD). The sNDA is supported by positive safety and efficacy data from several studies, including the phase 3 INTEGUMENT-1 and INTEGUMENT-2 studies. According to Lawrence Eichenfield, MD, with the UC San Diego School of Medicine, “Roflumilast cream if approved, has the potential to simplify the approach to [atopic dermatitis] disease control for children and adults.” The FDA granted the sNDA to Arcutis and has set a PDUFA target action date of July 7, 2024.
https://investors.arcutis.com/news-releases/news-release-details/fda-accepts-arcutis-supplemental-new-drug-application