dm+d

Unassigned

New Medicines

Duchenne muscular dystrophy

Information

New molecular entity
Santhera
Santhera

Development and Regulatory status

Phase II Clinical Trials
Pre-registration (Filed)
Pre-registration (Filed)
Yes
Yes
Oct 22Santhera has completed its rolling application in the US, setting up a possible approval and launch in H2 2023. If the FDA grants priority review, the review time will be cut from ten to six months. Timeline for possible US approval has slipped a little from predictions made earlier in the year, but Santhera remains on course to bring the drug to market in the US and EU in 2023. The company will need to raise additional funding to prepare the product for market entry, and it is predicted vamorolone could generate sales of more than $500 million in DMD alone [15].
Oct 22Filed in EU. Santhera expect to complete filing to US FDA by end of 2022 [15].
Jun 22FDA timeline likely delayed by four to six months due to manufacturing partner not being ready for FDA inspection required to deem the rolling application complete and ready for review. The company had previously expected to have approval via priority review by Q3 2022 [13].
Mar 22Santhera plans to submit MAA for vamorolone for the treatment of DMD to the EMA in Q3 22, leading to approval and launch in H2-2023. Santhera expects the first European launch country to be Germany [12].
Mar 22Santhera announce the initiation of a rolling new drug application (NDA) submission to the FDA for vamorolone for the treatment of Duchenne muscular dystrophy (DMD). Vamorolone for DMD has been granted Fast Track Designation by the FDA. Santhera expect to complete the NDA filing in Q2 22. Notification from the FDA on the acceptance of the filing for review is expected in August 2022. If request for Priority Review is accepted approval date could be Q1 23 [12].
Nov 21EU filing is planned before end of Q2 22 [11].
Sep 20US NDA submission is planned for Q4 2021 [8].
Sep 20Santhera Pharmaceuticals has acquired the worldwide rights to develop and commercialise vamorolone for the treatment of DMD and all other indications [7].
Oct 19Vamorolone has received Promising Innovative Medicine (PIM) designation for the treatment of Duchenne Muscular Dystrophy by the MHRA [6].
Oct 19Vamorolone is available under an expanded access protocol for male pts with duchenne muscular dystrophy (DMD). [2,3]
Aug 19Fast track and rare paediatric disease designations by the US FDA, for pts with DMD.[2,3]
Aug 14Orphan Drug Status in EU.[2]
Dec 11Orphan Drug Status in US.[2]

Category

Delta-9,11 glucocorticoid analogue which is a dissociative steroid (first in class). Designed to retains anti-inflammatory effect without growth stunting and immune suppression effects of corticosteroids.[2,3]
Duchenne Muscular Dystrophy (DMD) is one of the most common and severe forms of muscular dystrophy, affecting 15.9 to 19.5 per 100,000 live births. It almost exclusively occurs in males. People with the condition will usually only live into their 20s or 30s [1].
Duchenne muscular dystrophy
Oral

Further information

Yes

Trial or other data

Aug 22PII RCT (NCT03439670, n=133) found vamorolone showed improvements in multiple functional end points over 24-weeks vs placebo, with improvement from base-line to week 24 in in time to stand from supine velocity for 6mg/kg/day dose (least-squares mean velocity, 0.05 m/s; vs −0.01 m/s; p=0.002) [14].
Nov 21Santhera and ReveraGen announce positive topline results from completed VISION-DMD Study. Switching from prednisone to vamorolone after week 24 maintained efficacy and improved on multiple safety parameters including restoration of growth trajectory and reduction of behavioral changes up to week 48. Switching from placebo after week 24 resulted in an improvement of multiple efficacy outcome parameters with no apparent increase in the rate of TEAE up to week 48 [11].
Jun 21PIIb study designed to demonstrate efficacy and safety of vamorolone compared to placebo and prednisone (active control) met its primary endpoint. In the first 24-week double-blind period 121 ambulant boys aged 4 to <7 years with DMD were randomized to receive vamorolone (2 mg/kg/day or high dose 6 mg/kg/day) or prednisone (0.75 mg/kg/day) or placebo. The study continues for another 24 weeks with all patients receiving vamorolone [10].
Sep 20Results of PIIa extension study (NCT02760277) are available. DMD trial participants (4 to <7 years at entry) treated with 2 or 6mg/kg/day vamorolone for 18 months (n=23) showed clinical improvement of all motor outcomes from baseline to month 18 (primary outcome of time to stand velocity, p=0.012 [95% CI 0.010, 0.068 event/second])[9].
Sep 20Topline data from PIIb VISION DMD is expected Q2 2021 [8].
Oct 19Extension trial of NCT02760277 continues to show improvement in boys with DMD with findings which suggest that vamorolone results in improvement in DMD function, similar to that of corticosteroids, but with less side effects, including no stunting of the growth of DMD children.[3]
Sep 19PIIa open-label multiple-ascending-dose extension trial (N=48, NCT02760277) which evaluated the long-term safety and efficacy of vamorolone in steroid naive boys aged 4-7 with DMD published in Neurology. Dose levels were 0.25, 0.75, 2.0, and 6.0 mg/kg/day in an oral suspension formulation. The primary goal was to define optimal doses of vamorolone. The primary outcome for clinical efficacy was time to stand from supine velocity. All doses were safe and well tolerated. The 2.0–mg/kg/d dose group met the primary efficacy outcome of improved muscle function. A biomarker of bone formation, osteocalcin, increased in vamorolone-treated boys. Biomarkers for adrenal suppression and insulin resistance were also lower in vamorolone-treated boys with DMD vs. regular steroids from published data.[2,5]
Jun 18PIIb VISION DMD open label global trial initiated to evaluate the efficacy, safety, PK and PD of vamorolone in ambulant boys ages 4 to < 7 years with DMD (NCT03439670). The trial will recruit ~120 pts and will inc. 4 arms; vamorolone (2 mg/kg/day), vamorolone (6 mg/kg/day), prednisone (0.75 mg/kg/day) or placebo. After 24 weeks, the prednisone and placebo groups cross-over to low dose or high dose vamorolone and pts will be treated for 24 weeks. Primary endpoint for efficacy include measures of muscle function and body mass index (BMI). The DMD clinical program (VISION-DMD) is being developed by the company in collaboration between the CINRG group and Newcastle University. The estimated primary completion date is May 2020.[2,4]