dm+d

Unassigned

New Medicines

Zulresso Postnatal depressive disorder, moderate-to-severe

Information

Zulresso
New molecular entity
SAGE Therapeutics
SAGE Therapeutics

Development and Regulatory status

None
None
Launched
Feb 21Sage reports that revenue from sales of Zulresso has been negatively impacted by significant barriers arising from the complex requirements for treatment and by the rapid spread of COVID-19, and these factors are expected to continue to impact revenues negatively in the future. Plans for UK availability seem even more unlikely at present [4].
Feb 20In its latest annual report, Sage states that it continues to assess the development and regulatory pathway for brexanolone in the EU and its overall EU strategy in light of its overall portfolio and program priorities. Sage also cautions about the possible effects of Brexit on plans for launch in the UK. In light of these comments, it is unlikely that brexanolone will be available in the UK within at least the next 18-24 months [22].
Jul 19Launched in the US [21].

Jul 19: Launched in the US [21]


Q1 19: SAGE reports that it received scientific advice from the EMA in Oct 18 regarding the potential regulatory pathway for a marketing authorisation application filing in the EU. It anticipates having additional discussions with the EMA to help further clarify and evaluate what additional data and information would be needed, and what other requirements would need to be met, for a potential MAA filing. Expect this will take some time before filing can occur [20].


Mar 19: US launch planned for late June 2019 [19].


Mar 19: Approved by the FDA (subject to controlled substance scheduling) "for the treatment of postpartum depression (PPD) in adults." The product will be available only through a risk management scheme that requires the drug be administered by a health care provider in a certified health care facility. Planned launch is June 2019 as the drug is expected to be scheduled by the U.S. Drug Enforcement Administration (DEA), with an interim ruling from the DEA mandated within 90 days of approval [17].


Nov 18: FDA reassigns PDUFA action date of (19/3/2019) for brexanolone for postpartum depression [16].


Nov 18: The US FDA Psychopharmacologic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee voted for the approval of Zulresso (brexanalone). The committees based their joint recommendation on the safety and efficacy data from three placebo-controlled clinical studies.[15]


May 18: US FDA grant NDA Priority Review status with a PDUFA target date of 19/12/18 [13].


Apr 18: SAGE Therapeutics has submitted a New Drug Application (NDA) to the US FDA for brexanolone to treat postpartum depression (PPD).[11a]


Nov 17: Sage plans to apply for approval with the FDA early in 2018 [11].


Aug 17: Sage reports that it intends to file with the EMA for EU licensing following PRIME scientific discussions [8].


Dec 16: Sage reports an expedited development plan for brexanolone, following a Breakthrough Therapy meeting with the FDA; US filing for this indication is expected in 2018 [8].


Nov 16: EMA CHMP grants PRIME (PRIority MEdicine) status to allopregnanolone (SAGE-547) based on non-clinical and exploratory clinical data. PRIME status provides enhanced regulatory support for medicines that target an unmet medical need [7].


Sept 16: FDA grants Breakthrough Therapy Status on the basis of promising preliminary results from the PPD-202 PII trial [1].

Category

A neuroactive steroid and positive allosteric GABA-A receptor modulator
Frequency of post-natal depression is unclear, with values between 5.7% and 15% quoted; most women will not have severe symptoms [3,4].
Postnatal depressive disorder, moderate-to-severe
Intravenous infusion

Trial or other data

Aug 18Results of two PIII studies (NCT02942004 and NCT02942017) published in The Lancet. Pooled data (n=375) reported significant and clinically meaningful reductions in the Hamilton Rating Scale for Depression (HAM-D) score total score at 60 h for brexanolone vs placebo, with rapid onset of action and durable treatment response during the 30- day study period [14].

Nov 17: SAGE Therapeutics announces the success of two PIII trials of brexanolone in severe postpartum depression and moderate postpartum depression. Brexanolone hit the primary endpoint in both trials (reduction in the Hamilton Rating Scale for Depression [HAM-D] compared to placebo at 60 hours). Patients on brexanolone had a decrease from baseline in HAM-D scores of 14 to 20 points at 60 hours, and maintained them to 30 days in both trials [11].


Aug 17: results from PII trial published in full in the Lancet; generic name updated [10].


Jul 16: PIII trial program for this indication started, with two parallel trials investigating use in severe (NCT02942004, estimated n=120) and moderate (NCT02942017, estimated n=100) postpartum depression; each study will randomise patients to brexanolone or placebo with a primary outcome of change from baseline in Hamilton Rating Scale for Depression (HAMD) total score. Estimated primary completion date for both studies is December 2017 [9].


Jul 16: initial topline results from a small PII trial (NCT02614547) have been announced; in this randomised controlled double-blind study, women with severe post-natal depression received IV SAGE-547 or placebo: primary outcome was HAM-D score at 60 hours. Of 32 women enrolled, results were presented for 21 - in this group, there was a statistically significant reduction in HAM-D score vs. placebo, with a mean difference of 12 points [5,6].

Evidence based evaluations