Your monthly synopsis of new drugs expected to hit the market

At Prime Therapeutics (Prime), we’ve positioned ourselves to best prepare our clients to manage new drugs. Our clinical and trade relations teams keep a keen eye on drugs likely to be approved by the United States (U.S.) Food and Drug Administration (FDA).

Drug pipeline for August 2024

08/04/2024 afamitresgene autoleucel (afami-cel)

Adaptimmune Therapeutics’ first-in-class autologous T-cell therapy afami-cel is undergoing FDA Priority Review for the treatment of advanced synovial sarcoma. Afami-cel was granted Orphan Drug and Regenerative Medicine Advanced Therapy (RMAT) designations. Published data from the open-label, single-arm, phase 2 SPEARHEAD-1 trial reported, at a median follow-up of 32.6 months, the overall response rate (ORR) to afami-cel was 39% in treatment-experienced patients with HLA-A*02 and MAGE-A4 positive advanced synovial sarcoma.¹ Afami-cel is administered as a single intravenous (IV) dose after lymphodepletion. If approved, afami-cel will be the first treatment option for synovial sarcoma that targets MAGE-A4, which is present in up to 82% of synovial sarcoma tumors.

For more information, see the afamitresgene autoleucel Deep Dive in the April 2024 edition of the Quarterly Pipeline Quarterly Drug Pipeline – Prime Therapeutics LLC

08/07/2024 carbidopa/levodopa (IPX203)

Amneal is awaiting FDA approval of IPX203 for the treatment of Parkinson’s disease. This is the second review for IPX203, following a Complete Response Letter (CRL) issued by the FDA in July 2023 requiring additional safety information. IPX203 oral capsules contain immediate-release (IR) granules of carbidopa/levodopa (CD/LD) with a polymer to allow for rapid dissolution. It also contains extended-release (ER) beads of LD that are coated with a polymer to allow for slow release of the drug a mucoadhesive polymer to keep the granules adhered to the area of absorption longer, and an enteric coating to prevent the granules from disintegrating prematurely in the stomach. The randomized, double-blind, active-controlled RISE-OD trial, demonstrated that IPX203 increased good on-time per dose by a mean of 1.55 hours compared to IR CD/LD (p<0.001).² If approved, IPX203 will join several oral CD/LD products on the market, including extended-release CD/LD capsules (Rytary^®), also by Amneal.

08/11/2024 midomafetamine (MDMA)

Lykos is awaiting FDA approval of MDMA for use in combination with psychological intervention for the treatment of post-traumatic stress disorder (PTSD). MDMA is a psychoactive entactogen that promotes the release of monoamines and hormones in the brain (e.g., norepinephrine, dopamine, oxytocin, cortisol), which modulate emotional memory circuitry. The double-blind, phase 3 trials, MAPP1 and MAPP2, met their primary endpoints, demonstrating a significant improvement in the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score with MDMA compared to placebo (MAPP1: least square [LS] mean change, -4.4 versus -13.9, respectively [p<0.001]; MAPP2: LS mean change, -23.7 versus -14.8, respectively; [p<0.001]) at week 18. In both trials, significantly more patients who received MDMA no longer met the diagnostic criteria for PTSA and achieved PTSD remission compared to those who received placebo. The studies reported no potential for abuse. In each trial, MDMA was administered orally during three 8-hour psychotherapy sessions. MDMA was granted Breakthrough Therapy designation. If approved, it would be the first FDA-approved psychedelic agent. Also known as ecstasy, MDMA is currently a Schedule I Controlled Substance in the U.S. and will require rescheduling by the Drug Enforcement Administration (DEA) to allow for prescription use. However, states could have unique regulations to legalize and/or govern use. Of note, on June 4, 2024, the FDAs Psychopharmacologic Drugs Advisory Committee voted against approval of MDMA. In addition, on July 27, 2024, the Institute for Clinical and Economic Review (ICER) published a final evidence report on PTSD that did not favor use of MDMA. Both panels cited concerns of reliability of the results from the MAPP trials, and therefore, are uncertain of the safety and efficacy of MDMA for PTSD.

For more information, see the midomafetamine Deep Dive in the April 2024 edition of the Quarterly Pipeline Quarterly Drug Pipeline – Prime Therapeutics LLC

08/13/2024 denileukin diftitox (Lymphir)                              

Citius submitted an application to the FDA for their CD25-directed cytotoxin, Lymphir, for the treatment of relapsing or refractory cutaneous T cell lymphoma (CTCL) after at least one prior systemic therapy. This is the second review for Lymphir, following a CRL in July 2023 requiring enhanced product testing and additional controls. Denileukin diftitox contains the interleukin-2 (IL-2) receptor binding domain fused with diphtheria toxin fragments. Lymphir is a reformulated IV version of Eisai’s Ontak^®, which was voluntary removed from the U.S. market in 2014 due to protein folding observed during manufacturing. Lymphir is designed to avoid protein folding and has a reported 1.5 to 2 times greater specific bioactivity than Ontak. Like Ontak, Lymphir was granted Orphan Drug designation. In a phase 3 trial (NCT01871727), Lymphir 9 mcg/kg/day led to a 36.2% ORR (by independent review committee [IRC]) and a complete response rate of 6% in patients with Stage Ia to III CTCL. This is similar to the reported response rate for Ontak (ORR, 37% with 9 mcg/kg/day dose).

08/14/2024 nemolizumab

Galderma is awaiting FDA approval of nemolizumab for the treatment of prurigo nodularis, a rare, chronic inflammatory skin condition characterized by raised, hyperkeratotic lesions on the arms, legs and trunk.  Nemolizumab is a first-in-class monoclonal antibody that targets interleukin-31 receptor alpha (IL-31α). In the OLYMPIA trial program, 16 weeks of monotherapy with nemolizumab led to clinically and statistically significant improvements in both primary endpoints of peak-pruritus numerical rating scale (PP-NRS) compared to placebo (OLYMPIA 1, 58% versus 17%; OLYMPIA 2, 56% versus 21%; p<0.0001 for both) and investigator’s global assessment score (IGA) (OLYMPIA 1, 26% versus 7%; OLYMPIA 2, 38% versus 11%; p<0.0001 for both).³  Durable response was seen for up to 52 weeks. Nemolizumab is given subcutaneously (SC) every 4 weeks and has the potential for self-administration. Nemolizumab received Breakthrough Therapy designation and a Priority Review for prurigo nodularis. If approved, it will be the second biologic agent indicated for prurigo nodularis and will compete directly with dupilumab (Dupixent^®). Galderma has also submitted nemolizumab for the treatment of atopic dermatitis, with an FDA decision slated for December 2024.

For more information, see the nemolizumab Deep Dive in the April 2024 edition of the Quarterly Pipeline Quarterly Drug Pipeline – Prime Therapeutics LLC

08/14/2024 seladelpar

Seladelpar is an oral selective peroxisome proliferator-activated receptor-delta (PPAR-δ) agonist submitted to the FDA by Cymabay (subsidiary of Gilead) for the treatment of primary biliary cholangitis (PBC), including pruritus, in adults without cirrhosis or with compensated cirrhosis who are inadequate responders or intolerant to ursodeoxycholic acid (UDCA). In the double-blind RESPONSE trial, a once-daily dose of seladelpar 10 mg led to a significantly higher biochemical response rate compared to placebo (61.7% versus 20%, p<0.001).⁴ Biochemical response was defined as an alkaline phosphatase level < 1.67 times the upper limit of the normal (ULN) range, with a decrease of ≥ 15% from baseline, and a normal total bilirubin level at month 12. Seladelpar also resulted in a significantly greater reduction in pruritus compared to placebo. Seladelpar earned Breakthrough Therapy and Orphan Drug designations as well as a Priority Review by the FDA. If approved, seladelpar will be the second oral PPAR-δ agonist for PBC, following the approval of elafibranor (Iqirvo^®). Of note, in clinical trials elafibranor did not result in resolution of moderate to severe pruritus. Obeticholic acid (Ocaliva^®), an oral farnesoid X receptor (FXR) agonist, is also indicated for PBC.

For more information, see the seladelpar Deep Dive in the April 2024 edition of the Quarterly Pipeline Quarterly Drug Pipeline – Prime Therapeutics LLC

08/14/2024 palopegteriparatide (TransCon PTH)

The FDA is reviewing palopegteriparatide, a prodrug of parathyroid hormone (PTH [1-34]) by Ascendis, for the treatment of adults with hypoparathyroidism. This is the second review by the FDA for the Orphan Drug, following a CRL in May 2023 based on concerns of dosage reliability of the drug-device technology. The FDA also extended the review time period by 3 months to allow the FDA to evaluate additional information from a major amendment to the application. In the phase 3 PaTHway trial, 79% of patients in the palopegteriparatide group compared to 5% in the control group achieved serum calcium levels in the normal range (8.3–10.6 mg/dL) and independence from therapeutic levels of conventional therapy (p<0.0001) at week 26.⁵ Efficacy was maintained through week 52 of the trial’s open-label extension period.⁶ If approved, palopegteriparatide will be the only hormonal replacement therapy indicated to treat hypoparathyroidism available in the U.S. Recombinant human PTH 1-84 (Natpara^®; Takeda) was FDA approved for hypoparathyroidism in 2015, but was recalled in 2019 due to reports of rubber particulates in the cartridge and never returned to the U.S. market. Natpara carried a boxed warning for osteosarcoma, which has not been reported with palopegteriparatide.

08/20/2024 linvoseltamab

Regeneron is awaiting FDA decision for linvoseltamab for the treatment of relapsed or refractory multiple myeloma (RRMM). Linvoseltamab is a B-cell maturation antigen (BCMA) × CD3 bispecific antibody that facilitates T-cell activation and cancer cell death. The ongoing, open-label, phase 1/2 LINKER-MM1 trial, evaluated IV-administered linvoseltamab in patients who had received at least three prior lines of therapy. At a median follow-up of 14.3 months, linvoseltamab 200 mg demonstrated an ORR of 71%, with a 50% complete response rate and a median duration of response of 29.4 months.⁷ Cytokine release syndrome, neutropenia and anemia were the most common adverse events reported in the trial. Linvoseltamab was granted Fast Track designation as well as a Priority Review. If approved, it will likely compete with the SC-administered BCMA×CD3 bispecific antibodies elranatamab-bcmm (Elrexfio^™) and teclistamab-cqyv (Tecvayli^®) in the fifth-line setting.

08/28/2024 axatilimab

Syndax submitted axatilimab to the FDA for the treatment chronic graft-versus-host disease (cGVHD) after failure of at least two prior lines of systemic therapies. The FDA granted axatilimab a Priority Review and Fast Track and Orphan Drug designations. Axatilimab is a monoclonal antibody that targets colony stimulating factor 1 receptor (CSF-1R), which plays a key role in sustained inflammation and tissue injury during cGVHD. In the open-label, phase 2 AGAVE-201 trial, 74% of patients treated with axatilimab 0.3 mg/kg IV every 2 weeks (the likely approved dosage) achieved an objective response at 24 weeks (6 cycles), 1% of patients achieved a complete response and 60% of responders maintained their response at 12 months.⁸ If approved, axatilimab will provide a new mechanism in combating cGVHD, a disorder that continues to have unmet medical need.