Travere Therapeutics Announces Voluntary Pause of Enrollment in the Phase 3 HARMONY Study of Pegtibatinase Related to Commercial Manufacturing Scale-Up
Travere Therapeutics (Nasdaq: TVTX) has announced a voluntary pause in enrollment for its Phase 3 HARMONY Study of pegtibatinase, a potential treatment for classical homocystinuria (HCU). This decision was made to address necessary process improvements in manufacturing scale-up for commercial production. Currently enrolled patients will continue to receive study medication from unaffected small-scale batches.
The pause was initiated after the company determined that the desired drug substance profile was not achieved in the recent scale-up process. Travere expects to restart enrollment in the HARMONY Study no earlier than 2026. As a result, the company anticipates a reduction in research and development expenses by more than $30 million in 2025 compared to 2024. Travere's cash reserves of $325.4 million as of June 30, 2024, are expected to support operations into 2028.
Travere Therapeutics (Nasdaq: TVTX) ha annunciato una pausa volontaria nell'arruolamento per il suo studio di fase 3 HARMONY su pegtibatinase, un potenziale trattamento per l'omocistinuria classica (HCU). Questa decisione è stata presa per affrontare i miglioramenti necessari nei processi di produzione su larga scala per la produzione commerciale. I pazienti attualmente arruolati continueranno a ricevere il farmaco dello studio da lotti piccoli e non influenzati.
La pausa è stata avviata dopo che l'azienda ha determinato che il profilo della sostanza farmaceutica desiderato non era stato raggiunto nel recente processo di scala. Travere prevede di riavviare l'arruolamento nello studio HARMONY non prima del 2026. Di conseguenza, l'azienda si aspetta una riduzione delle spese di ricerca e sviluppo di oltre 30 milioni di dollari nel 2025 rispetto al 2024. Le riserve di cassa di Travere pari a 325,4 milioni di dollari al 30 giugno 2024, dovrebbero supportare le operazioni fino al 2028.
Travere Therapeutics (Nasdaq: TVTX) ha anunciado una pausa voluntaria en la inscripción para su Estudio HARMONY de Fase 3 sobre pegtibatinase, un tratamiento potencial para la homocistinuria clásica (HCU). Esta decisión se tomó para abordar las mejoras necesarias en los procesos de fabricación a gran escala para la producción comercial. Los pacientes actualmente inscritos continuarán recibiendo el medicamento del estudio a partir de lotes pequeños y no afectados.
La pausa se inició después de que la empresa determinara que el perfil de sustancia farmacéutica deseado no se logró en el reciente proceso de escalado. Travere espera reiniciar la inscripción en el Estudio HARMONY no antes de 2026. Como resultado, la empresa anticipa una reducción en los gastos de investigación y desarrollo de más de 30 millones de dólares en 2025 en comparación con 2024. Las reservas de efectivo de Travere de 325,4 millones de dólares al 30 de junio de 2024, se espera que sustenten las operaciones hasta 2028.
- Currently enrolled patients can continue receiving study medication
- Anticipated reduction in R&D expenses by over $30 million in 2025
- Cash reserves of $325.4 million expected to support operations into 2028
- Voluntary pause in enrollment for Phase 3 HARMONY Study
- Desired drug substance profile not achieved in recent scale-up process
- Earliest restart of enrollment pushed to 2026
- Delay in planned investments for clinical enrollment and large-scale production
Insights
The voluntary pause in enrollment for Travere Therapeutics' Phase 3 HARMONY study of pegtibatinase is a significant setback for the company's pipeline. This delay, caused by manufacturing scale-up issues, pushes the potential restart of enrollment to 2026, substantially extending the timeline for this key program.
While the company maintains confidence in pegtibatinase's potential as a first disease-modifying therapy for classical homocystinuria (HCU), this delay will likely impact investor sentiment and the company's near-term prospects. The expected
Positively, Travere's cash position of
The manufacturing scale-up issues encountered by Travere Therapeutics highlight the complexities involved in transitioning from small-scale production to commercial-scale manufacturing for biologics. The failure to achieve the desired drug substance profile during scale-up is a critical concern that requires careful analysis and resolution.
This situation underscores the importance of robust process development and the challenges of maintaining product quality and consistency at larger scales. The company's decision to pause enrollment to address these issues is prudent, as it prevents potential complications that could arise from using suboptimal material in clinical trials.
The timeline for resolving these manufacturing challenges, with enrollment restart not expected until 2026, suggests that significant process optimization and validation work is required. This extended timeline may also involve regulatory interactions to ensure that any process changes meet regulatory requirements for pivotal trial material and eventual commercial production.
Company to host conference call today at 4:30 p.m. ET
SAN DIEGO, Sept. 26, 2024 (GLOBE NEWSWIRE) -- Travere Therapeutics, Inc., (Nasdaq: TVTX) today announced a voluntary pause of enrollment in the Phase 3 HARMONY Study evaluating pegtibatinase for the treatment of classical homocystinuria (HCU). The voluntary enrollment pause enables the Company to work to address necessary process improvements in manufacturing scale-up to support commercial scale manufacturing as well as full enrollment in the HARMONY Study. Patients currently enrolled in pegtibatinase studies continue to receive study medication from small scale batches which are unaffected by the scale-up process. Currently enrolled patients will be able to continue on study medication as scheduled for the duration of the trials they are participating in.
The voluntary enrollment pause was enacted following the Company’s determination that the desired drug substance profile was not achieved in the recent scale-up process. The Company is in the process of notifying all study investigators of the decision to pause enrollment of new patients into the study until additional material is available.
“We believe the potential for pegtibatinase to become the first disease-modifying therapy for classical HCU remains unchanged. Our internal team and external manufacturing partners have extensive biologics expertise, and we are confident that we will be able to make the necessary manufacturing process improvements to continue with this pivotal program. We remain committed to supporting the patients currently enrolled in our clinical trials while working with our manufacturing partners to optimize our commercial-scale manufacturing process,” said Bill Rote, Ph.D., senior vice president of research and development at Travere Therapeutics.
The Company expects to further evaluate the necessary commercial process improvements to enable the continuation of the Phase 3 program and anticipates the earliest date to restart enrollment in the Phase 3 HARMONY Study will be in 2026. Previously planned investments related to clinical enrollment in HARMONY and large-scale production are expected to be delayed beyond 2025. Together with the expected decline in costs associated with the development of sparsentan as the Phase 3 programs advance towards completion, the Company now estimates that research and development expenses may be reduced by more than
Conference call information
Travere Therapeutics will host a conference call and webcast today, Thursday, September 26, 2024 at 4:30 p.m. ET to discuss the voluntary pause in enrollment. To participate in the conference call, dial +1 (323) 994-2093 (U.S.) or +1 (888) 394-8218 (International), confirmation code 5880214. The webcast can be accessed on the Investor page of Travere’s website at ir.travere.com/events-presentations. Following the live webcast, an archived version of the call will be available for 30 days on the Company’s website.
About Classical Homocystinuria
Classical homocystinuria (HCU) is a rare genetic metabolic disorder caused by a deficiency in the enzyme cystathionine beta synthase (CBS). CBS is a pivotal enzyme that is essential for the management of methionine and cysteine in the body. Classical HCU leads to toxic levels of homocysteine that can result in life-threatening thrombotic events such as stroke, pulmonary embolism and deep vein thrombosis, ophthalmologic and skeletal complications, as well as developmental delay. Current treatment options are limited to protein-restricted diet and use of vitamin B6 and betaine.
About Pegtibatinase
Pegtibatinase is an investigational PEGylated, recombinant enzyme replacement therapy designed to address the underlying cause of classical HCU. In preclinical studies, pegtibatinase has demonstrated an ability to reduce total homocysteine levels and improve clinical parameters. In December 2023 the Company initiated the pivotal Phase 3 HARMONY Study to support the potential approval of pegtibatinase for the treatment of classical HCU. The HARMONY Study is a global, randomized, multi-center, double-blind, placebo-controlled Phase 3 clinical trial designed to evaluate the efficacy and safety of pegtibatinase as a novel treatment to reduce total homocysteine (tHcy) levels. In May 2023 the Company announced that data from four patients treated with the highest dose of pegtibatinase in the Phase 1/2 COMPOSE Study showed a clinically meaningful
About Travere Therapeutics
At Travere Therapeutics, we are in rare for life. We are a biopharmaceutical company that comes together every day to help patients, families and caregivers of all backgrounds as they navigate life with a rare disease. On this path, we know the need for treatment options is urgent – that is why our global team works with the rare disease community to identify, develop and deliver life-changing therapies. In pursuit of this mission, we continuously seek to understand the diverse perspectives of rare patients and to courageously forge new paths to make a difference in their lives and provide hope – today and tomorrow. For more information, visit travere.com.
Forward-Looking Statements
This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995. Without limiting the foregoing, these statements are often identified by the words “on-track,” “positioned,” “look forward to,” “will,” “would,” “may,” “might,” “believes,” “anticipates,” “plans,” “expects,” “intends,” “potential,” or similar expressions. In addition, expressions of strategies, intentions or plans are also forward-looking statements. Such forward-looking statements include, but are not limited to, references to: the potential for pegtibatinase to become the first disease-modifying therapy for classical HCU; statements and expectations regarding future process improvements in manufacturing scale-up to support commercial scale manufacturing as well as full enrollment in the HARMONY Study, and related timing expectations; statements regarding ongoing clinical trials, including statements regarding medication for patients currently enrolled in such trials; and statements and expectations related to future research and development expenses and the expected timing thereof, including with respect to investments related to clinical enrollment in HARMONY and large scale production, and the expected decline in costs associated with the development of sparsentan as the Phase 3 programs advance towards completion; and expectations regarding cash runway. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements are risks and uncertainties associated with manufacturing processes and improvements, and risks related to the regulatory review and approval process, as well as risks and uncertainties associated with the Company’s business and finances in general, the success of its commercial products and risks and uncertainties associated with its preclinical and clinical stage pipeline. Specifically, the Company faces risks associated with the challenges of manufacturing scale-up, the ongoing commercial launch of FILSPARI, market acceptance of its commercial products including efficacy, safety, price, reimbursement, and benefit over competing therapies, as well as risks associated with the successful development and execution of commercial strategies for such products. The risks and uncertainties the Company faces with respect to its preclinical and clinical stage pipeline include risk that the Company’s clinical candidates will not be found to be safe or effective and that current or anticipated future clinical trials will not proceed as planned. The Company also faces the risk that its cash runway might not last as long as currently anticipated and the risk that it will be unable to raise additional funding that may be required to complete development of any or all of its product candidates, including as a result of macroeconomic conditions; risks relating to the Company’s dependence on contractors for clinical drug supply and commercial manufacturing; uncertainties relating to patent protection and exclusivity periods and intellectual property rights of third parties; risks associated with regulatory interactions; and risks and uncertainties relating to competitive products, including current and potential future generic competition with certain of the Company’s products, and technological changes that may limit demand for the Company’s products. The Company also faces additional risks associated with global and macroeconomic conditions, including health epidemics and pandemics, including risks related to potential disruptions to clinical trials, commercialization activity, supply chain, and manufacturing operations. You are cautioned not to place undue reliance on these forward-looking statements as there are important factors that could cause actual results to differ materially from those in forward-looking statements, many of which are beyond our control. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Investors are referred to the full discussion of risks and uncertainties, including under the heading “Risk Factors”, as included in the Company’s most recent Form 10-K, Form 10-Q and other filings with the Securities and Exchange Commission.
Contact Info
| Media: 888-969-7879 mediarelations@travere.com | Investors: 888-969-7879 IR@travere.com |
FAQ
What is the reason for Travere Therapeutics (TVTX) pausing enrollment in the HARMONY Study?
Will current participants in Travere Therapeutics' (TVTX) pegtibatinase studies continue to receive treatment?
When does Travere Therapeutics (TVTX) expect to restart enrollment in the Phase 3 HARMONY Study?
How will the enrollment pause affect Travere Therapeutics' (TVTX) financial outlook?
