Viking Therapeutics Announces Results from Phase 1b Clinical Trial of VK0214 in Patients with X-ALD
Viking Therapeutics announced positive results from its Phase 1b clinical trial of VK0214, a novel TRβ agonist, in patients with X-linked adrenoleukodystrophy (X-ALD). The study showed VK0214 to be safe and well-tolerated with once-daily dosing over 28 days. Significant reductions were observed in plasma levels of very long-chain fatty acids (VLCFAs) and other lipids compared to placebo.
Key findings include:
- Significant reductions in mean VLCFA levels at both 20 mg/day and 40 mg/day doses
- Reductions in C26:0-LPC, a key diagnostic marker
- Decreases in LDL-C, ApoB, and Lp(a) levels
- Mild to moderate treatment emergent adverse events
- Lower incidence of gastrointestinal adverse events in VK0214-treated subjects (11%) compared to placebo (33%)
The company views these results as encouraging and plans to explore next steps for VK0214 in X-ALD treatment.
Viking Therapeutics ha annunciato risultati positivi dal suo trial clinico di Fase 1b su VK0214, un nuovo agonista TRβ, in pazienti affetti da adrenoleucodistrofia X-linked (X-ALD). Lo studio ha dimostrato che VK0214 è stato sicuro e ben tollerato con somministrazione una volta al giorno per 28 giorni. Sono state osservate significative riduzioni nei livelli plasmatici di acidi grassi a catena molto lunga (VLCFA) e di altri lipidi rispetto al placebo.
I principali risultati includono:
- Riduzioni significative nei livelli medi di VLCFA sia con dosi di 20 mg/giorno che di 40 mg/giorno
- Riduzioni nei livelli di C26:0-LPC, un marker diagnostico chiave
- Decrementi nei livelli di LDL-C, ApoB e Lp(a)
- Eventi avversi emergenti da trattamento lievi a moderati
- Incidenza inferiore di eventi avversi gastrointestinali nei soggetti trattati con VK0214 (11%) rispetto al placebo (33%)
La società considera questi risultati incoraggianti e prevede di esplorare i prossimi passi per VK0214 nel trattamento dell'X-ALD.
Viking Therapeutics anunció resultados positivos de su ensayo clínico de Fase 1b de VK0214, un nuevo agonista de TRβ, en pacientes con adrenoleucodistrofia ligada al X (X-ALD). El estudio mostró que VK0214 fue seguro y bien tolerado con una dosis diaria durante 28 días. Se observaron reducciones significativas en los niveles plasmáticos de ácidos grasos de cadena muy larga (VLCFA) y otros lípidos en comparación con el placebo.
Los hallazgos clave incluyen:
- Reducciones significativas en los niveles promedio de VLCFA tanto con dosis de 20 mg/día como de 40 mg/día
- Reducciones en C26:0-LPC, un marcador diagnóstico clave
- Disminuciones en los niveles de LDL-C, ApoB y Lp(a)
- Eventos adversos emergentes leves a moderados
- Menor incidencia de eventos adversos gastrointestinales en sujetos tratados con VK0214 (11%) en comparación con placebo (33%)
La compañía considera estos resultados alentadores y planea explorar los próximos pasos para VK0214 en el tratamiento de la X-ALD.
Viking Therapeutics는 X-연관 아드레노류코디스트로피(X-ALD) 환자를 대상으로 한 VK0214의 1b상 임상 시험에서 긍정적인 결과를 발표했습니다. 이 연구는 VK0214가 28일 동안 하루에 한 번 투여되었을 때 안전하고 잘 견뎌졌다는 것을 보여주었습니다. 플라세보와 비교하여 매우 긴 사슬 지방산(VLCFA) 및 기타 지질의 혈장 수준에서 유의미한 감소가 관찰되었습니다.
주요 발견 사항은 다음과 같습니다:
- 20 mg/일 및 40 mg/일의 두 가지 용량에서 평균 VLCFA 수준의 유의미한 감소
- 주요 진단 마커인 C26:0-LPC의 감소
- LDL-C, ApoB 및 Lp(a) 수준의 감소
- 경미한에서 중간 정도의 치료 유발 부작용
- VK0214 치료를 받은 피험자에서 발생한 위장 부작용의 비율이 플라세보(33%)에 비해 낮은 11%
회사는 이러한 결과를 고무적이라고 보고 VK0214의 X-ALD 치료를 위한 다음 단계를 탐색할 계획입니다.
Viking Therapeutics a annoncé des résultats positifs de son essai clinique de Phase 1b sur VK0214, un nouvel agoniste TRβ, chez des patients atteints d’adrenoleucodystrophie liée à l’X (X-ALD). L'étude a montré que VK0214 était sécuritaire et bien toléré avec une dose quotidienne pendant 28 jours. Des réductions significatives des niveaux plasmatiques de d'acides gras à très longue chaîne (VLCFA) et d'autres lipides ont été observées comparativement au placebo.
Les résultats clés comprennent :
- Des réductions significatives des niveaux moyens de VLCFA à des doses de 20 mg/jour et de 40 mg/jour
- Des réductions dans C26:0-LPC, un marqueur diagnostique clé
- Des diminutions des niveaux de LDL-C, ApoB et Lp(a)
- Des événements indésirables de traitement légers à modérés
- Une incidence plus faible d'événements indésirables gastro-intestinaux chez les sujets traités par VK0214 (11%) par rapport au placebo (33%)
L'entreprise considère ces résultats comme encourageants et prévoit d'explorer les prochaines étapes pour VK0214 dans le traitement de l'X-ALD.
Viking Therapeutics hat positive Ergebnisse aus seiner Phase-1b-Studie zu VK0214, einem neuartigen TRβ-Agonisten, bei Patienten mit X-chromosomaler Adrenoleukodystrophie (X-ALD) angekündigt. Die Studie zeigte, dass VK0214 sicher und gut verträglich ist, mit einer einmal täglichen Dosis über 28 Tage. Bedeutende Reduktionen der Plasmaspiegel von sehr langkettigen Fettsäuren (VLCFAs) und anderen Lipiden im Vergleich zum Placebo wurden beobachtet.
Die wichtigsten Ergebnisse umfassen:
- Bedeutende Reduktionen der mittleren VLCFA-Spiegel sowohl bei 20 mg/Tag als auch bei 40 mg/Tag
- Reduktionen in C26:0-LPC, einem wichtigen diagnostischen Marker
- Senken der LDL-C-, ApoB- und Lp(a)-Spiegel
- Leichte bis mäßige behandlungsbedingte unerwünschte Ereignisse
- Niedrigere Inzidenz von gastrointestinale unerwünschte Ereignisse bei mit VK0214 behandelten Probanden (11 %) im Vergleich zum Placebo (33 %)
Das Unternehmen betrachtet diese Ergebnisse als ermutigend und plant, die nächsten Schritte für VK0214 in der Behandlung von X-ALD zu prüfen.
- Significant reductions in VLCFA levels, including C26:0-LPC, a key diagnostic marker for X-ALD
- Decreases in plasma lipids (LDL-C, ApoB, and Lp(a) levels) observed
- VK0214 demonstrated safety and tolerability over 28 days of once-daily dosing
- Lower incidence of gastrointestinal adverse events in VK0214-treated subjects compared to placebo
- None.
Insights
The Phase 1b trial results for VK0214 in X-ALD patients are highly encouraging. The drug demonstrated significant reductions in very long-chain fatty acids (VLCFAs), particularly C26:0-LPC, a key diagnostic marker for X-ALD. This is important as VLCFAs are considered disease biomarkers in X-ALD.
The observed reductions in plasma lipids, including LDL-C (19.4-20.2% reduction), ApoB (16.3-22% reduction) and Lp(a) (22.1-26.8% reduction), suggest potential broader cardiometabolic benefits. These improvements were statistically significant compared to placebo.
Importantly, VK0214 showed a favorable safety profile, with treatment-emergent adverse events reported as mild to moderate. The 28-day study duration is relatively short, so longer-term studies will be necessary to fully assess efficacy and safety.
These results position VK0214 as a promising candidate for X-ALD treatment, a rare genetic disorder with therapeutic options. The next steps will likely involve larger, longer-duration trials to confirm these initial findings.
Viking Therapeutics' positive Phase 1b results for VK0214 represent a significant milestone in their drug development pipeline. This news is likely to have a positive impact on the company's valuation and investor sentiment.
Key financial implications include:
- Potential market opportunity: X-ALD is a rare disease with treatment options, suggesting a high unmet medical need and potential for premium pricing if approved.
- Pipeline advancement: Successful early-stage results increase the probability of further development, potentially leading to a valuable asset in Viking's portfolio.
- Broader applications: The observed effects on lipid profiles (LDL-C, ApoB, Lp(a)) hint at potential applications beyond X-ALD, possibly expanding the drug's market potential.
- Future funding: Positive data may attract partnership opportunities or improve terms for future capital raises.
Investors should note that while promising, these are early-stage results. Significant R&D investment and regulatory hurdles remain before potential commercialization. The stock may see increased volatility as the market digests this news.
Reductions in Very Long-Chain Fatty Acids and Plasma Lipid Levels Observed After 28 Days of Once Daily Dosing
VK0214 Shown to be Safe and Well-Tolerated in 28-Day Study
Highlights from the study results include:
Reductions in VLCFAs
In addition to safety and tolerability, the study included an exploratory assessment of changes in plasma levels of VLCFAs after 28 days of dosing. VLCFAs are considered biomarkers of disease in patients with X-ALD. Treatment with VK0214 resulted in significant reductions in mean VLCFA levels at both doses evaluated, 20 mg/day and 40 mg/day, compared to placebo. Importantly, cohorts receiving VK0214 demonstrated reductions in mean plasma levels of the 26 carbon lysophosphatidyl choline (C26:0-LPC) derivative, a key diagnostic marker.
Percent Change from Baseline in VLCFAs Following 28 Days of Treatment of VK0214
Placebo1 (n=6) | 20 mg (n=8) | 40 mg (n=9) | |
C22:0 | 4.0 % | -16.6 % | -19.5 % |
p-value vs. placebo2 | - | 0.0097 | 0.0042 |
C24:0 | 5.2 % | -12.8 % | -18.0 % |
p-value vs. placebo | - | 0.0162 | 0.0029 |
C26:0 | 20.8 % | -17.4 % | -17.6 % |
p-value vs. placebo | - | 0.0145 | 0.0117 |
C26:0-LPC3 | 23.1 % | -8.4 % | -14.8 % |
p-value vs. placebo | - | 0.0427 | 0.0105 |
Notes: 1) Least squares mean change from baseline to Day 28. 2) Two-sided t-test using mixed model for repeated measures. 3) C26:0-LPC data for 20 mg, 40 mg cohorts include results from n=7, n=8 subjects, respectively. |
Reductions in Plasma Lipids
In addition to VLCFA changes, subjects who received VK0214 demonstrated reductions in other plasma lipids. Mean reductions relative to baseline and placebo were observed for low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and lipoprotein (a) [Lp(a)] following 28 days of treatment.
Percent Change in Lipid Markers Following 28 Days of Treatment of VK0214
Placebo1 (n=6) | 20 mg (n=9) | 40 mg (n=9) | |
LDL-C | 4.7 % | -19.4 % | -20.2 % |
p-value vs. placebo2 | - | <0.0001 | <0.0001 |
ApoB | 8.6 % | -16.3 % | -22.0 % |
p-value vs. placebo | - | 0.0004 | <0.0001 |
Lp(a) | 17.5 % | -22.1 % | -26.8 % |
p-value vs. placebo | - | 0.0199 | 0.0105 |
Notes: 1) Least squares mean change from baseline to Day 28. 2) Two-sided t-test using mixed model for repeated measures. |
Safety and Tolerability
VK0214 demonstrated encouraging safety and tolerability following 28 days of once-daily dosing. Treatment emergent adverse events were reported as mild to moderate; one subject in the placebo cohort experienced a wrist fracture that was characterized as a severe adverse event. Gastrointestinal adverse events were slightly higher among placebo subjects (
"We are excited to report these initial results evaluating VK0214 in patients with adrenomyeloneuropathy," said Brian Lian, Ph.D., chief executive officer of Viking. "Patients receiving VK0214 demonstrated progressive improvement in plasma levels of very long chain fatty acids in the relatively brief treatment period evaluated in this study. In addition, VK0214 continued to show benefits on broader plasma lipids, such as LDL-C, important for overall cardiometabolic health. Consistent with prior clinical results in healthy volunteers, VK0214 was shown to be safe and well-tolerated in this 28-day study. We look forward to exploring next steps with this important compound."
The Phase 1b trial was a multi-center, randomized, double-blind, placebo-controlled study in adult male patients with the adrenomyeloneuropathy (AMN) form of X-ALD. The study enrolled patients across three cohorts: placebo, VK0214 20 mg daily, and VK0214 40 mg daily. The primary objectives were to evaluate the safety and tolerability of VK0214 in subjects with AMN, when administered once-daily over a 28-day dosing period. Secondary objectives included an evaluation of the pharmacokinetics of VK0214 following 28 days of dosing in this population. An exploratory objective was to evaluate the effects of VK0214 on plasma levels of VLCFAs in subjects with AMN.
About X-ALD
X-ALD is a rare and often fatal metabolic disorder characterized by a breakdown in the protective barriers surrounding brain and nerve cells; a process known as demyelination. In X-ALD, mutations in a gene known as ABCD1 lead to dysfunction of the adrenoleukodystrophy protein (ALDP), an important peroxisomal transporter. In patients, this dysfunction leads to an accumulation of VLCFAs, which can trigger a rapid, inflammatory demyelination, resulting in cognitive impairment, motor skill deterioration, and even death. Research in disease models has shown that increasing the expression of a related gene known as ABCD2, which encodes a compensatory transporter called the adrenoleukodystrophy related protein (ADLRP), can result in normalization of VLCFA levels. Activation of the thyroid hormone beta receptor, as observed in patients treated with VK0214, has been shown to increase the expression of ABCD2 resulting in reductions in VLCFA levels. X-ALD is estimated to occur in approximately 1 in 17,000 births. Currently there are no pharmacologic treatments approved for the disease.
About Viking Therapeutics, Inc.
Viking Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on the development of novel first-in-class or best-in-class therapies for the treatment of metabolic and endocrine disorders, with three compounds currently in clinical trials. Viking's research and development activities leverage its expertise in metabolism to develop innovative therapeutics designed to improve patients' lives. Viking's clinical programs include VK2809, a novel, orally available, small molecule selective thyroid hormone receptor beta agonist for the treatment of lipid and metabolic disorders. The compound successfully achieved both the primary and secondary endpoints in a recently completed Phase 2b study for the treatment of biopsy-confirmed non-alcoholic steatohepatitis (NASH) and fibrosis. In a Phase 2a trial for the treatment of non-alcoholic fatty liver disease (NAFLD) and elevated LDL-C, patients who received VK2809 demonstrated statistically significant reductions in LDL-C and liver fat content compared with patients who received placebo. Viking is also developing VK2735, a novel dual agonist of the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors for the potential treatment of various metabolic disorders. Data from a Phase 1 and a Phase 2 trial evaluating VK2735 (dosed subcutaneously) for metabolic disorders demonstrated an encouraging safety and tolerability profile as well as positive signs of clinical benefit. The company is also evaluating an oral formulation of VK2735 in a Phase 1 trial. In the rare disease space, Viking is developing VK0214, a novel, orally available, small molecule selective thyroid hormone receptor beta agonist for the potential treatment of X-linked adrenoleukodystrophy (X-ALD). VK0214 is currently being evaluated in a Phase 1b clinical trial in patients with the adrenomyeloneuropathy (AMN) form of X-ALD.
For more information about Viking Therapeutics, please visit www.vikingtherapeutics.com.
Forward-Looking Statements
This press release contains forward-looking statements regarding Viking Therapeutics, Inc., under the safe harbor provisions of the
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SOURCE Viking Therapeutics, Inc.
FAQ
What were the main results of Viking Therapeutics' Phase 1b trial for VK0214 (VKTX)?
How did VK0214 affect VLCFA levels in X-ALD patients (VKTX)?
What were the safety outcomes of the VK0214 Phase 1b trial (VKTX)?
How did VK0214 affect plasma lipid levels in the Phase 1b trial (VKTX)?
