Rare Disease Pharmacy Insights

Vascarta's groundbreaking transdermal curcumin gel, VAS-101, presents an innovative, cost-effective potential treatment for sickle cell disease. The gel showed promising results in preclinical tests with sickle cell mice, significantly mitigating pain and inflammation while stabilising red blood cells. This drug candidate, a non-opioid, stands apart from expensive and complex gene therapies, offering a safer alternative with minimal side effects. Unlike traditional oral curcumin, VAS-101 utilises a unique delivery system—akin to bypassing the usual traffic jam—ensuring effective absorption, quicker relief, and a potential solution to the chronic complications of sickle cell disease.

The supportive preclinical outcomes have sparked plans for clinical trials in individuals with sickle cell disease. Set to be initiated by the Foundation for Sickle Cell Disease and Research, these trials aim to explore the gel's efficiency when administered topically and sublingually. With its increased bioavailability and ability to bypass the liver's metabolic "roadblocks", VAS-101 could become a game-changer in sickle cell treatment, offering a pragmatic solution free from the drawbacks of existing therapies.

Gene-editing treatments hold promising potential for the future of rare diseases, particularly those with a genetic basis like Angelman syndrome and other neurodevelopmental disorders. Yale researchers, including Dr. Yong-Hui Jiang and Dr. Jiangbing Zhou, are pioneering advancements in gene-editing technology to target genetic defects. Their work focuses on developing non-viral, chemical-based delivery systems, such as STEP technology, which uses chemicals instead of traditional viral vectors. This approach is gaining attention for its potential to treat neurogenetic diseases, offering a glimmer of hope in an often overlooked field.

Despite the advancements in gene-editing technology, significant challenges remain. The safety of CRISPR technology, ensuring minimal off-target effects, and resource availability are critical obstacles in bringing these treatments from research to clinical application. Nevertheless, with support from the NIH and other philanthropic efforts, researchers remain optimistic about future breakthroughs. Innovations in gene-editing could lead to more focused and efficient treatments, driving a tangible shift in how rare diseases are approached, potentially benefiting countless patients worldwide.

Onco360 has been chosen as a national specialty pharmacy partner for GOMEKLI (mirdametinib), approved by the FDA for treating both adults and children suffering from neurofibromatosis type 1 (NF1) with symptomatic plexiform neurofibromas. As a MEK1/2 inhibitor, GOMEKLI addresses a critical need for those impacted by this genetic condition, which often results in painful and debilitating tumours. Onco360’s partnership with SpringWorks Therapeutics marks another significant addition to its expanding portfolio of rare disease therapies.

The FDA’s approval follows the ReNeu study, which showed GOMEKLI to be effective, achieving response rates of 41% in adults and 52% in children. Despite some mild to moderate side effects like rash and musculoskeletal pain, the treatment significantly improves quality of life for NF1 patients. With Onco360's expertise in oncology pharmacy, this collaboration promises enhanced access and support for individuals with limited treatment options, illustrating progress in addressing rare disease challenges.

Travere Therapeutics is making a bold move to seek FDA approval for its rare kidney disease drug, Filspari, despite setbacks in clinical trials. The drug, which targets focal segmental glomerulosclerosis (FSGS), failed to meet the primary endpoint in its pivotal Phase III DUPLEX study, showing only a slight non-significant eGFR improvement over its competitor. Yet, Travere is undeterred, as Filspari demonstrated a significant 50% reduction in proteinuria compared to 32% with the control drug, a result linked strongly to reduced risk of kidney failure. The company hopes this proteinuria reduction will suffice to win FDA approval, aiming to submit a supplemental NDA by the end of Q1 2025.

Should the FDA grant approval, Filspari would become the first drug officially approved for FSGS treatment. This prospect has already buoyed Travere’s stock price, jumping 14% following the announcement. While the company had to cut staff to focus on Filspari’s development in other areas, notably IgAN, success in this venture could place them firmly on the map in the rare disease market, with projections of substantial sales growth by 2030.

Orphan medicines, pivotal for treating rare diseases, face challenges such as hefty costs and complex clinical trial designs due to small, dispersed patient populations. Incentives have propelled progress, yet affordability remains a pressing issue, exacerbated by inconsistent willingness-to-pay thresholds across nations. The complexities of rare disease treatments are compounded by diverse genetic profiles and high development costs. But light at the end of the tunnel shines as regulatory bodies embrace real-world evidence to streamline approvals and the potential of genetic profiling to tailor treatments gains traction.

The pharmaceutical world acknowledges repurposing existing drugs as a plausible path to curb costs, highlighted by innovative gene therapies that cater to monogenic disorders. Multifaceted collaborations between governments, industry, and advocacy groups emerge as vital in surmounting these hurdles. Despite milestones achieved, the quest for balance between funding orphan medicines and maintaining broader healthcare services looms. The quintessential role of patient organisations in championing this cause ensures that the spotlight remains on improving access and developing effective therapies for rare disease patients.