Mallinckrodt's woes persist as reformulated opioid painkiller fails to pass FDA muster

Mallinkrodt 改良阿片类止痛药未通过 FDA 审查,致股价在上市前下跌约9%

2018-12-13 07:43:43 endpoint News


The FDA’s reluctance with prescription painkillers at a time the United States is swept by a tsunami of opioid abuse, overdose and addiction was on full display on Wednesday, when the regulator rejected Mallinckrodt’s $MNK abuse-deterrent opioid painkiller, soliciting more data from the UK drugmaker. The drug under scrutiny was a tweaked version of Roxicodone, an immediate-release formulation of the commonly abused opioid oxycodone that was approved by the FDA in 2000. This reformulation was designed to deter abuse via snorting or injecting. In its CRL, the agency “provided guidance regarding areas of further evaluation necessary to resubmit the NDA for further review,” Mallinckrodt said. Shares of the Staines-upon-Thames-based company, which said it would spin off its specialty business last week, were down about 9% pre-market. The announcement follows another setback: one of two late-stage drugs Mallinckrodt won as part of its $1.2 billion acquisition of Sucampo failed a pivotal study in November. The CRL for the painkiller does not come as a complete surprise. In a review last month, FDA staff pointed out that the agency had not made any definitive conclusions regarding whether the drug could be manipulated for intravenous abuse, as Mallinckrodt had not yet submitted data from several key studies as part of its NDA. A panel of independent experts reviewing the drug a few days later concurred, suggesting the drug be labeled as an abuse deterrent only via the nasal route. This could culminate in a similar situation to that of Endo’s $ENDP Opana, which was withdrawn from the market last year at the behest of the FDA, after post-market data showed the reformulated opioid painkiller was being abused intravenously at a higher rate, even as rates of nasal abuse fell. But Mallinckrodt is planning to plough ahead. The company intends to request a meeting in the coming weeks with the regulator to discuss its next steps, it said on Wednesday. On average, opioid overdoses kill 115 Americans per day, and the economic burden of prescription opioid misuse alone is a hefty $78.5 billion each year, including the healthcare costs, lost productivity, and criminal justice involvement, according to the CDC. As the number of opioid-related deaths mount, the FDA has largely changed its tune on the oft’ misused class of drugs by amending its prescribing recommendations,tracking the number of prescriptions, tightening scrutiny and requiring manufacturers to develop abuse-deterrent formulations. However, the agency is not quite imposing a blanket ban on all things opioid. Last month, it approved AcelRx Pharmaceuticals $ACRX painkiller Dsuvia, a drug 10-times more potent than fentanyl, which in turn is a synthetic opioid pain reliever that is 50 to 100 times more potent than morphine. The controversial approval was sanctioned despite heightening concern and fiery criticism (from a host of critics including a handful of US senators) on the grounds that the drug — which was developed in collaboration with the Department of Defense — is a sublingual formulation, making it ideal for military use, noted FDA Commissioner Scott Gottlieb.
美国遭受鸦片类药物滥用、过量服用和成瘾的海啸席卷之际, FDA 对处方止痛药的不情愿在周三得到了充分展示。监管机构拒绝了 Malinckrodt 以 MNK 美元的滥用威慑阿片类药物止痛药,要求英国制药商提供更多数据。 正在审查的药物是一种改良版的罗西酮,一种立即释放的制剂,普遍滥用的阿片羟考酮于2000年获得 FDA 批准。这种改良法的目的是通过打鼾或注射来阻止滥用.在 CRL 中,该机构“就重新提交 NDA 进行进一步审查所需的进一步评估领域提供了指导,” Mallinkrodt 说。 这家总部位于泰晤士河畔的 Staines 公司上周宣布将剥离其专业业务,其股价在上市前下跌了约9%。在此之前,该公司还遭遇了另一次挫折:作为以12亿美元收购 Sucampo 的交易的一部分,两种处于后期阶段的药物 Mallinkrodt 中的一种未能在11月完成一项关键研究。 止痛药的 CRL 并不完全出人意料。在上个月的一次审查中, FDA 的工作人员指出, FDA 还没有对该药是否可能被操纵用于静脉药物滥用做出任何明确的结论,因为 Mallinkrodt 尚未提交作为 NDA 一部分的几项关键研究的数据。几天后,一个独立专家小组对该药物进行了审查,认为该药物只有通过鼻腔途径才能被标记为滥用威慑力。 这可能导致与去年应 FDA 要求退出市场的 Endo 公司价值1美元的 ENDP Opana 类似的情况,此前市场后的数据显示,重新设计的阿片类止痛药在静脉内被滥用的比率更高,即使鼻腔滥用的比率下降。 但 Mallinkrodt 正计划向前推进。该公司周三表示,计划在未来几周内与监管机构召开会议,讨论其下一步措施。 美国疾控中心的数据显示,平均而言,阿片类药物过量每天导致115名美国人死亡,仅处方类阿片类药物滥用的经济负担每年就高达785亿美元,其中包括医疗费用、生产力损失和刑事司法参与。随着鸦片类药物相关死亡人数的增加, FDA 通过修改处方建议、追踪处方数量、加强审查以及要求制造商开发滥用威慑配方,在很大程度上改变了对经常被滥用的药物类别的控制。 然而,该机构并不完全禁止所有鸦片类物质。上个月,该公司批准了宏基制药( AcelRx Pharmaceuticals )的价格为 ACRX 止痛药 Dsuvia ,这是比芬太尼效力10倍的药物,而芬太尼又是一种合成阿片类止痛药,效力比吗啡高50至100倍。FDA 专员斯科特•戈特利布( Scott Gottlieb )指出,这一有争议的批准得到了批准,尽管遭到了更多的关注和激烈的批评(包括一些批评人士,包括一些美国参议员),理由是这种与国防部合作开发的药物是一种舌下的制剂,使其成为军事用途的理想药物。