FDA Grants Fast Track Designations to Soligenix and Cabaletta Bio

Rare Daily Staff

The U.S. Food and Drug Administration granted Fast Track designations to two companies for experimental therapeutics in development for rare diseases: Solgenix SGX945 for Behcet’s disease and Cabaletta Bio’s CABA-201 for dermatomyositis.

Fast track is a designation that the FDA reserves for a drug intended to treat a serious or life-threatening condition and one that demonstrates the potential to address an unmet medical need for the condition and is intended to facilitate the development and expedite the review of new drugs and biologics. It allows for a company to submit a new drug application (NDA) on a rolling basis, permitting the FDA to review sections of the NDA prior to receiving the complete submission. Additionally, NDAs for fast track development programs ordinarily will be eligible for priority review, which imparts an abbreviated review time of approximately six months.

Soligenix received FDA’s Fast Track designation for its SGX945 (dusquetide) development program for the treatment of oral lesions of Behçet’s disease.

“Behçet’s disease is an unmet medical need in which the underlying vasculitis leads to ulceration of the mucous membranes and skin, with up to 18,000 people in the U.S. and as many as one million people worldwide affected by this incurable disease,” said Christopher Schaber, president and CEO of Soligenix. “Given our promising results with aphthous ulcers in oral mucositis, we are hopeful dusquetide will have a role to play in helping underserved patients suffering from this difficult to treat and chronic disease and look forward to initiating the Phase 2 clinical study in 2024.”

Behçet’s disease is commonly known as an inflammatory disorder of the blood vessels (vasculitis). Often first diagnosed in young adults, its effects and severity will wax and wane over time. Major signs and symptoms usually include mouth sores, skin rashes and lesions, genital sores, leg ulcers, and eye inflammation. It is a painful disease, directly impacting the patient’s quality of life and ability to productively engage in life activities, including work. Behçet’s disease is thought to be an autoimmune disease with both genetic and environmental factors. It is most common along the “Silk Road” in the Middle East and East Asia, including Turkey, Iran, Japan and China. There are approximately 18,000 known cases of Behçet’s Disease in the U.S. and 80,000 in Europe, with as many as one million people worldwide living with Behçet’s Disease.

Dusquetide and SGX942 is an innate defense regulator (IDR), a new class of short, synthetic peptides. It has a novel mechanism of action whereby it modulates the body’s reaction to both injury and infection towards an anti-inflammatory, anti-infective, and tissue healing response. IDRs have no direct antibiotic activity but, by modulating the host’s innate immune system responses, increase survival after infections caused by a broad range of bacterial Gram-negative and Gram-positive pathogens. It also accelerates resolution of tissue damage following exposure to a variety of agents including bacterial pathogens, trauma, and chemo- and/or radiation therapy.

Dusquetide has demonstrated safety and tolerability in a Phase 1 clinical study in 84 healthy human volunteers. In phase 2 and 3 clinical studies with SGX942 in over 350 subjects with oral mucositis due to chemoradiation therapy for head and neck cancer, positive efficacy results were demonstrated, including potential long-term ancillary benefits.

FDA granted Cabaletta Bio two separate Fast Track designations to CABA-201, an investigational 4-1BB-containing fully human CD19-CAR T cell therapy, for the treatment of patients with dermatomyositis to improve disease activity and for the treatment of patients with systemic sclerosis (SSc) to improve associated organ dysfunction.

“The additional Fast Track designations for CABA-201 in both dermatomyositis and systemic sclerosis, the second and third Fast Track Designations for CABA-201, provide the opportunity for expedited development and review of CABA-201 for the treatment of these autoimmune indications where there is a significant unmet need, despite currently available therapies,” said David Chang, chief medical officer of Cabaletta.

CABA-201 is designed to deplete CD19-positive B cells following a one-time infusion, which may enable an “immune system reset” with the potential for durable remission off therapy in patients with autoimmune diseases. To date, Cabaletta has received clearance from the FDA for Investigational New Drug (IND) applications for CABA-201 in multiple autoimmune conditions including systemic lupus erythematosus (SLE), myositis, SSc and generalized myasthenia gravis (gMG). Cabaletta is conducting four phase 1/2 clinical trials with a total of nine cohorts that can advance simultaneously, employing a similar parallel cohort design and starting dose of 1 x 106 cells/kg without a dose escalation requirement.

Dermatomyositis (DM) is an autoimmune disease that can lead to severe functional impairment that may be life-threatening despite the best available standard of care. It is characterized by a skin rash along with muscle inflammation and weakness. Although the pathophysiology of DM is not well understood, it is thought to be a subtype of myositis that is driven by B cells. DM affects approximately 43,000 patients in the U.S. alone, and typically affects middle-aged individuals, particularly women. Current treatment typically involves medications to suppress the immune system and/or chronic intensive therapies such as intravenous immunoglobulin, or IVIg. Despite these therapies, a significant portion of DM patients have disease that remains refractory to existing medications.

SSc is a rare and potentially fatal chronic autoimmune disease characterized by progressive skin and internal organ fibrosis that can be life-threatening, including interstitial lung disease, pulmonary hypertension, and scleroderma renal crisis. Although the etiology of SSc is not well understood, the pathogenic role of autoantibodies and B cells in SSc provides a rationale for studying CAR T therapy in this population. SSc affects approximately 88,000 patients in the U.S., and typically affects middle-aged individuals, particularly women. Standard treatment options, which have modest effects, include generalized immunosuppressive agents or drugs targeted to specific symptomatic manifestations. Autologous hematopoietic stem cell transplant may provide some benefits in organ involvement, but carries significant risks, including mortality, infertility, and secondary autoimmune disease, limiting its potential to be applied broadly. Due to the lack of adequate treatments, the risk of mortality in systemic sclerosis remains high, with an average survival of approximately 12 years following diagnosis.