MS-2 Step (mifepristone and misoprostol)
MS-2 Step is approved for the following extension of indications:
-an extension of the current indication for the medical termination of an intrauterine pregnancy from up to 63 days' gestation to up to 70 days' gestation; and
-a new indication for the medical management of missed miscarriage up to 70 days' gestation, determined by ultrasound equivalence rather than menstrual period.
MS-2 Step contains the active ingredients mifepristone and misoprostol.
MS-2 Step is available in Australia for the medical ending of an early pregnancy (medical termination of pregnancy) of up to 63 days (9 weeks) of pregnancy.
This approval expands the use of MS-2 Step in two ways.
First, MS-2 Step is now approved to end an intrauterine pregnancy up to 70 days of gestation. This extends the previous approved use by 7 days.
Second, MS-2 Step is now approved to medically manage missed miscarriage up to 70 days of gestation. A missed miscarriage is when the embryo or foetus has died, but the pregnancy tissue remains inside the uterus and has not yet been passed from the body. For this use, gestational age is determined by ultrasound rather than by the date of the last menstrual period.
MS-2 Step contains two active ingredients, mifepristone and misoprostol.
Mifepristone (taken as one 200 milligram tablet) works by blocking progesterone, a hormone essential to support pregnancy.
Misoprostol, taken as four 200 microgram tablets 36 to 48 hours later, causes the uterus to contract and helps the body pass the pregnancy tissue
The Sponsor provided published studies, national and international clinical guidelines and real-world use of the medicines to support the safety and efficacy of MS-2 Step. The literature search strategy was accepted by the TGA as per the TGA’s guidance for literature-based submissions. The evidence was sufficient for assessing whether MS-2 Step could be used safely and effectively up to 70 days of gestation.
The medical termination of an intrauterine pregnancy up to 70 days of gestation
Overall, there was strong evidence which showed that mifepristone and misoprostol were effective for the medical termination of pregnancies between 64 and 70 days’ gestation.
For example, in one large study, successful termination of pregnancy occurred in 93.5% of women at 57 to 63 days of gestation and 92.8% of women at 64 to 70 days of gestation. Another large study also supported use up to 70 days, with complete termination of pregnancy rates above 93.2% in the 64 to 70 days’ gestation group. These results showed that MS-2 Step did not become less effective in the 64 to 70 days of gestation interval when compared to the 57 to 63 days of gestation interval.
The safety information did not reveal any new concerns in women with pregnancies between 64-70 days gestation who were given mifepristone followed by misoprostol for the purposes of medical termination of pregnancy. The reported side effects were consistent with the known effects of MS-2.
The submitted evidence supported approval of MS-2 Step for medical termination of pregnancy up to 70 days of gestation. The use of MS-2 Step in the medical termination of an intrauterine pregnancy up to 70 days’ gestation was recommended by the Australian Committee on Medicines. The TGA decided that MS-2 step can be registered in Australia for this purpose.
The medical management of miscarriage up to 70 days of gestation
The Sponsor proposed the same two-medicine regimen for the medical management of all types of miscarriage: 200 mg of mifepristone taken orally, followed 36 to 48 hours later by 800 micrograms of misoprostol in a single buccal dose (where the medicine is kept between the cheek and gum and absorbed through the lining of the mouth).
In one large study in women with missed miscarriage, women who took mifepristone followed by misoprostol were more likely to complete the miscarriage without needing any further treatment than women who took placebo followed by misoprostol. They were also less likely to need surgery. Women received misoprostol vaginally, orally or under the tongue. This study showed that mifepristone improves the effectiveness of misoprostol in managing missed miscarriage.
Another study showed that mifepristone followed by misoprostol was more effective than misoprostol alone for medical management of missed miscarriage in women with miscarriages between 5-12 weeks’ gestation. Although misoprostol was delivered vaginally and not via the buccal route, the study supported the clinical value of the two-medicine regimen.
An analysis which combined the results of multiple published studies found that mifepristone followed by misoprostol was more effective in achieving complete miscarriage than waiting for the miscarriage to complete naturally. This benefit applied to missed miscarriages only.
The clinical guidelines from national and international organisations, including the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG), the National Institute for Health and Care Excellence (UK) and the American College of Obstetricians and Gynecologists support the use of mifepristone and misoprostol (administered buccally or vaginally) in missed miscarriage.
The safety data for using mifepristone and misoprostol to manage early miscarriage did not reveal any safety concerns. The reported side effects were consistent with the known effects of MS-2.
The submitted published data, clinical guidelines, real-world data, and the known safety profile of mifepristone and misoprostol support the use of MS-2 Step in missed miscarriage up to 70 days of gestation. The use of MS-2 Step in missed miscarriage was recommended by the Australian Committee on Medicines. The TGA decided that MS-2 step can be registered in Australia for this purpose.
More detailed information on why the TGA approved MS-2 Step will be published in the upcoming Australian Public Assessment Report (AusPAR).
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The PI document provides essential prescribing information for health professionals, including details on dosage recommendations, pregnancy category, contraindications, precautions and potential side effects.
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