The FDA grants Priority Review designation to applications for medicines that have the potential to provide significant improvements in the treatment of serious conditions.
Priority Review is associated with an accelerated six-month review period compared to the standard ten-month review period. If approved, teprotumumab would be the first FDA-approved medicine for the treatment of active TED.
“Priority Review for the teprotumumab BLA is another positive step toward our goal to make a difference in the lives of people who are living with active TED – a painful, debilitating and vision-threatening rare disease,” said Timothy Walbert, chairman, president and chief executive officer, Horizon. “The accelerated review timeline is particularly important given that there is no FDA-approved medical treatment for TED and the window of time for treatment is limited before patients experience potentially long-term, permanent damage to their eyes.”
The FDA has completed its filing review and determined that the application is sufficiently complete to permit a substantive review. Therefore, a priority review classification was established and the Prescription Drug User Fee Act (PDUFA) goal date is March 8, 2020.
In its letter, the FDA noted that it has established internal review timelines for FDA internal milestone meetings (e.g., filing, planning, mid-cycle, team and wrap-up meetings) and that these timelines described in current FDA guidelines are flexible and subject to change based on workload and other potential review issues (e.g., submission of amendments).
The letter further notes that the FDA will inform Horizon of any necessary information requests or status updates following the milestone meetings or at other times, as needed, during the process. If major deficiencies are not identified during the review, the FDA plans to communicate proposed labeling and, if necessary, any post marketing requirement/commitment requests by late December 2019.
The FDA also indicated that it is currently planning to hold an advisory committee meeting to discuss the application per guidelines for new molecular entities.1 Additionally, the FDA notified Horizon that, at this time, it has not identified any potential review issues, although its current filing review is only a preliminary evaluation of the application and is not indicative of deficiencies that may be identified during the review.
The accepted BLA for teprotumumab includes results from the Phase 3 confirmatory clinical trial, called OPTIC (Treatment of Graves’ Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study), as well as positive Phase 2 results.
The OPTIC study found that significantly more patients treated with teprotumumab had a meaningful improvement in proptosis, or bulging of the eye, as compared with placebo (82.9% of teprotumumab patients compared to 9.5% of placebo patients). All secondary endpoints were also met, including reduced diplopia (double vision), improved quality of life (QoL) and reductions in Clinical Activity Score (CAS). Teprotumumab was generally well tolerated; the majority of adverse events were mild or moderate, manageable and resolved during or after treatment.
Results of the OPTIC study were presented during the 2019 American Association of Clinical Endocrinologists (AACE) Annual Scientific & Clinical Congress. The OPTIC study was initiated after the Phase 2 study demonstrated clinically meaningful and highly statistically significant results in reducing proptosis and in the symptoms of active TED (pain, swelling, redness and inflammation) as measured by Overall Treatment Response (combined CAS and proptosis improvement). The Phase 2 study was published in The New England Journal of Medicine in May 2017.
Source: Company Press Release
与标准的10个月审查期相比，优先审查与加速6个月审查期有关。如果获得批准，替普妥鲁木单抗将成为第一个获得 FDA 批准的治疗活动性 TED 的药物。
Horizon 公司董事长、总裁兼首席执行官蒂莫西•沃尔伯特( Timothy Walbert )表示：“对于我们的目标而言，对患有 TED 的人来说，对他们的生活产生影响是另一个积极的步骤。 TED 是一种痛苦的、令人衰弱的、威胁视力的罕见疾病。”“考虑到没有 FDA 批准的 TED 药物治疗，而且在患者经历潜在的长期、永久的眼睛损害之前，治疗的时间窗口是有限的，因此加速审查时间尤为重要。”
FDA 已经完成了申报审查，并确定申请已经足够完整，可以进行实质性审查。因此，建立了优先审评分类，处方药使用者费法（ PDUFA ）目标日期为2020年3月8日。
FDA 在信中指出，它已经为 FDA 内部里程碑会议（例如归档、规划、中期周期、团队和总结会议）制定了内部审查时间表，并且当前 FDA 指南中描述的这些时间表是灵活的，并且根据工作量和其他潜在审查问题（例如提交修正案)。
信中还指出， FDA 将在里程碑会议之后或根据需要在其他时间向 Horizon 通报任何必要的信息请求或状态更新。如果在审查过程中没有发现重大缺陷， FDA 计划在2019年12月底之前传达建议的标签以及任何上市后要求/承诺要求。
FDA 还表示，目前正计划召开一个咨询委员会会议，讨论新分子实体的每项准则的应用。1此外， FDA 通知 Horizon ，目前还没有发现任何潜在的审查问题，尽管目前的备案审查只是对申请的初步评估，并不表明审查期间可能发现的缺陷。
已被接受的用于治疗特异瘤的 BLA 包括3期确认临床试验的结果，称为 OPTIC （治疗 Graves'Orbitpathy （甲状腺眼病）以减少特异瘤侵袭性的随机、安慰剂对照、临床研究），以及2期阳性结果。
OPTIC 的研究发现，与安慰剂相比，接受过特替鲁木单抗治疗的患者中，与安慰剂相比，有显著改善的是眼球突出或眼球突出（特替鲁木单抗患者的82.9%，安慰剂患者的9.5%）。所有次要终点也得到满足，包括减少双视力，改善生活质量（ QoL ）和减少临床活动评分（ CAS ）。肿瘤一般耐受性良好，大部分不良事件轻微或中度，可控，治疗期间或治疗后得到解决。
在2019年美国临床内分泌医师协会（ AACE ）年度科学与临床大会上发表了 OPTIC 研究结果。第二阶段研究显示，临床上有意义且具有高度统计学意义的结果显示，通过整体治疗反应（ CAS 和 Protosis 联合改善）测量， OPTIC 研究在减少丙泊松症和活动性 TED （疼痛、肿胀、红肿和炎症）症状方面取得了显著的进展。第二阶段研究于2017年5月发表于《新英格兰医学杂志》。