Do you ever know that she has something to say, she has something to say, she is in pain, she needs your care.They say women can hold half the sky, but in the course of human reproduction, women assume more responsibility.Because of this, some diseases are unique to women or the main incidence of people, which requires you and me in the pharmaceutical industry he gave more attention and pay.
This article briefly introduces the newly approved or investigational drugs and devices for common gynecological and obstetrical diseases, hoping to help you learn more about female compatriots.
The "reaction stoppage" that shocked the world in the 1950s and 1960s not only became the hero of Dr. Frances Kathleen Oldham Kelsey, Ph.D., M.D., but also established the FDA's global lead in drug regulation, leaving more than 10,000 "seal babies" and their families with unlimited pain.Although this event has been mentioned repeatedly for more than half a century, it always reminds the pharmaceutical industry of the importance of safety research in the R & D process of new products, and also warns the significance of scientific and rigorous review by pharmaceutical product regulatory authorities.
However, people often ignore the point that the cause of the event is: Nausea and Vomiting of Pregnancy (NVP), commonly known as morning sickness or morning sickness, known as the ancients.This is the nausea of a pregnant woman in the first trimester.Vomiting, etc., is usually most severe when you get up in the morning.According to different literature analysis, about 70% -80% of pregnant women worldwide experience morning sickness, while the proportion of hyperemesis gravidarum is about 1.1%.How difficult this stage is, women who have had pregnancy experience, as for those who do not have the relevant experience can consult a person.
Of course, being a woman can be much more painful than that.
Auntie is here, leave me alone
When he was in junior high school, the boys found that the girls were very affectionate and had the privilege of taking time off from the gym teacher, watching or staying in the classroom.Later, the boys gradually learned that girls always have a few days a month called "aunt" a relative to visit regularly, and to the girls bring a lot of inconvenience.The most common manifestation is dysmenorrhea (Dysmenorrhea, Menstrual Cramps), and ibuprofen can be taken in severe cases.Pain relieving drugs such as paracetamol or hormonal contraceptives.There is also a performance that requires the use of an "aunt's towel, if you want to move", but if the flow is too large, it can be a disease.
Menstrual flow exceeds 80 ml per month, which is menorrhagia.However, how to judge 80ml is more subjective, about every 1-2 hours on the wet through a large sanitary napkin or tampon, it means more menstrual flow.According to different literature statistics, menorrhagia occurs in 9% -30% of women of childbearing age. The incidence increases with age and peaks before menopause.
Tranexamic acid, which became a hot topic some time ago, is due to a discussion about whether it is compliant to add it to toothpaste.Clinically, this is an old drug used to stop bleeding during surgery. It was discovered as early as 1962 by Japanese female scientist Utako Okamoto.However, it was not approved for menorrhagia until November 2009 by the US FDA, Lysteda from Ferring, a world-renowned obstetrics and gynecology pharmaceutical company.
In addition, estrogen seems to be essential for the treatment of female-related disorders, as is menorrhagia.In March 2012, the U.S. FDA approved Bayer Natazia for the treatment of menorrhagia.One course of this product includes 28 tablets, including
2 dark yellow tablets containing 3 mg estradiol valerate
Red contains 2 mg of estradiol valerate and 2 mg of dienogest in 5 tablets
17 Tablets light yellow containing 2 mg estradiol valerate and 3 mg dienogest
2 dark red tablets containing 1 mg estradiol valerate, and
2 white blank tablets
Treatments include not only drugs but also devices such as the Cerene cryotherapy instrument developed by Channel Medsystems.Unlike existing endometrial ablation devices, the product does not require heat or anesthesia for less than three minutes.When the probe reaches the bottom of the uterus, nitrogen dioxide is released so that the bag expands rapidly and comes into contact with the endometrium.Nitrogen dioxide can cool the target tissue, while the inflatable bag can avoid unnecessary damage to the surrounding tissue.
In 2017, Channel Medsystems received a harvest. First, in March, it completed the key clinical trials in the United States and began to collect and sort out data for application for marketing. Soon after, it received the EU CE mark in June for premenopausal menorrhagia in pregnant women.In November, it struck a deal with Boston Scientific, an industry giant that already has a 20% stake, to buy the remaining 80% for $275 million once it was approved by the U.S. FDA on September 30, 2019.But as the brilliant year of 2017 comes to a successful end, it suddenly comes to light that the company's vice president of quality is suspected of embezzling $3 million through shell companies.Although the company took action and said it did not affect its plans to launch the product in the United States, Boston Scientific believes it was fraudulently announced to cancel the acquisition.Channel Medsystems sued Boston Scientific on Sept. 12, 2018 for demanding that it fulfill a previously agreed acquisition agreement after negotiations failed.The court session is scheduled for April 15, 2019.
It's hard to have a baby
The most magical thing in the world is no doubt the birth and development of life.To open branches and scatter leaves is the instinct of life.However, let's not say "dry and wet, exhausted their efforts, look at them safe and sound adults, teach them to behave in a decent manner, and even expect them to shaoqiao bright ancestral industry," even though modern medicine is so developed, just in October pregnant.The first childbirth had already left her mother at the door.
If you want to inherit your offspring, first of all you can get pregnant.However, nearly 10% of couples worldwide are suffering from infertility for various reasons.In China, about one in eight couples still do not conceive a year after trying to conceive.In addition, after the release of the two-child policy for elderly couples to prepare for pregnancy, the infertility rate in China is expected to rise from 15.5% in 2017 to 18.1% in 2023.Many of them hope that assisted reproductive technologies such as In Vitro Fertilization, commonly known as IVF technology, refer to in vitro fertilization in which sperm and eggs are removed to form fertilized eggs, which are then cultured in vitro for a period of time to transfer the formed embryos into the mother's uterus.However, due to various factors, IVF is not always successful.
Nolasiban, an oral oxytocin receptor antagonist developed by Swiss company ObsEva, which is dedicated to female reproductive health, is expected to reduce uterine contractions, enhance uterine blood flow, and improve endometrial acceptance of embryo implantation.ObsEva received global interest from Merck in Germany in 2013.The results of a completed phase 3 trial showed a 7-11% improvement in success compared to placebo.Although only about 10%, but for infertile couples has increased a lot of hope.ObsEva has initiated another Phase 3 clinical trial in Europe in November 2018 and plans to submit a marketing application in Europe by the end of 2019.
Myovant is developing MVT-602, an oligopeptide kisspeptin agonist that can be used in assisted reproductive technology to treat female infertility.Kisspeptin is a natural peptide that stimulates gonadotropin-releasing hormone (GnRH) release.This hormone is essential for pubertal development and normal reproductive function, including spermatogenesis.Follicular maturation and ovulation, as well as estrogen and progesterone production in women and testosterone production in men.The project is in phase 2a clinical trials and preliminary data are expected to be published in the first half of 2019.In fact, this Myovant company dedicated to women's health is not only the project in hand, but also the legendary color behind it.
However, despite the hardships, successful pregnancy is only the first step, in the course of pregnancy will experience many bumps.
Also known as pre-eclampsia, refers to 24 weeks after pregnancy, the occurrence of edema.Hypertension.Proteinuria and headache.Dizziness.Vomiting.Epigastric discomfort.Visual impairment or blood pressure systolic above 160 mm Hg (21.3 kPa).Without timely and effective intervention, there is a risk of developing eclampsia and even maternal death.According to various literature reports, the incidence of preeclampsia is between 2% and 10%.Preeclampsia plus eclampsia is one of the four leading causes of maternal death (the rest is postpartum hemorrhage.Infections and unsafe induction of labor), accounting for 10% – 20%.
AMAG Pharmaceuticals Inc. is developing DIF, a digoxin immunizing antigen-binding fragment (ovine) for the treatment of preeclampsia, from Velo Bio, another U.S. company.The latter has initiated a phase 2b/3a clinical trial in mid-2017 and is expected to release data in the first half of 2020 and plans to submit a marketing application to the US FDA in the second half of 2020.Earlier, the US Food and Drug Administration had granted orphan drugs and fast-track access.
In humans, the normal gestational period is 40 weeks, and delivery at less than 37 weeks of gestation is considered premature.According to the pregnancy cycle, premature delivery can be divided into:
Less than 28 weeks, extremely preterm, about 5%
28-31 weeks, severe preterm delivery, approximately 15%
32-33 weeks, moderate preterm delivery, approximately 20%
34-36 weeks, slight premature delivery, accounting for about 60% -70%
There are approximately 15 million premature infants worldwide each year, with a wide range of preterm birth rates from 5% to 18% across countries.Of these, 5% are in northern Europe, while more than 15% are in sub-Saharan Africa and some Asian countries.The rate of premature delivery in China is about 7%, close to 6.2% in Europe, even better than 10.6% in North America.But even so, given China's large population base and the annual number of new born population, the absolute number of premature infants per year is still as high as about 1.2 million, about a third of India, ranking second in the world.
Makena Hydroxyprogesterone Caproate Injection, another product of AMAG Pharmaceuticals, was approved by the U.S. FDA in February 2011 for the prevention of preterm labor.The originator of this product was Hologic, which was later acquired by AMAG.
OBE022, being developed by Swiss company ObsEva, is a novel oral prostaglandin F2alpha (PGF2α) receptor antagonist that is currently in phase 2a clinical trials for the treatment of preterm labor.PGF2α contracts the myometrium, causing an increase in metabolites before and during amniotic fluid formation.PGF2α also upregulates the enzyme causing cervical dilatation and membrane rupture.By specifically inhibiting the PGF2 alpha receptor and safely controlling inflammation, OBE022 not only inhibits uterine contractions but also prevents cervical changes resulting from preterm labor.
In the completed Phase 2a, Part 1, open-label clinical trial, 8 of 9 women with symptoms of preterm labor did not deliver within 7 days of treatment, and only 1 did so on Day 2.Phase 2a, part II, double-blind clinical trial has been initiated in some countries in Europe and Asia.
In October, a baby is delivered.New life arrives, the whole family is immersed in the joy of Tim Ding, this time focusing on the newborn, but do not forget the need to continue to pay attention to maternal health.
"Alive" is an important work in Chinese contemporary literature, and it is also an important work in the history of new Chinese film.One of the plot is this: Fugui's daughter Feng Xia dystocia, son-in-law Wan Erxi to be kept in a barn hungry for three days of senior obstetrician and gynecologist Dr. Wang.The hungry Doctor Wang ate the seven steamed buns bought by Fugui in one breath and drank the water again.At this moment, although Fengxia gave birth to a boy, but there was a massive postpartum hemorrhage, in the face of this emergency situation, a group of red guard nurses grabbed power, and experienced Dr. Wang has fainted.Poor Fengxia, because a high fever became deaf and dumb when he was a child, he could not make a groan and finished his life.
Postpartum hemorrhage is defined as vaginal blood loss of more than 500 ml within 24 hours after delivery.As mentioned earlier, postpartum hemorrhage is one of the four major causes of maternal death.The global incidence of postpartum hemorrhage accounts for about 2% of all deliveries.Postpartum haemorrhage accounts for 1 in 1,000 births, mostly in less developed regions, and 1 in 100,000 in developed regions.
Because of the high risk of maternal death from postpartum hemorrhage in underdeveloped regions, it is important to facilitate the transport and storage of drugs.Who conducted a study of heat-stable carbetocin, which was provided free of charge by the company, in conjunction with Merck, USA, and Pfizer, Switzerland.The drug does not need to be stored in a refrigerator and can be stored at 30 degrees Celsius and 75 percent relative humidity for 3 years.Because less developed areas are also concentrated in areas with high temperature and humidity, and medical conditions are backward, this drug is of great benefit in reducing maternal death from postpartum hemorrhage in this area.
The older drug mentioned above, tranexamic acid, is also suitable for the treatment of postpartum hemorrhage. The mechanism is one thing.However, since postpartum haemorrhage is an emergency, the dosage form is given as an injectable form, whereas for menorrhagia, tablets are given orally.
In addition to the use of drugs for hemostatic therapy, American company Alydia is developing a device.This product uses vacuum to generate negative pressure, prompting the uterus to rapidly contract and naturally close the vascular opening, so as to achieve the effect of rapid hemostasis.In the pilot study, 10 women were able to control postpartum hemorrhage quickly and effectively within minutes.In September 2018, the company completed $10 million round B financing to support 510 (K) applications to the U.S. Food and Drug Administration.The trial plans to recruit 107 women in the United States.
Although the birth of a child is a happy thing, but about 70% -80% of new mothers will have mood swings after childbirth, this phenomenon is called "Baby Blue" (infantile depression), generally for several hours to several days, can be self-resolving, more reassurance, no treatment.Another 10-15% of new mothers will suffer from postpartum depression, mainly manifested as depressed mood.No fun.Forgetfulness.Anxiety.Insomnia and irritability, lasting weeks or even months, require treatment.Severe cases can lead to mental illness, even suicide, requiring hospitalization, which is about 0.1% -0.2%.
In fact, there are many drugs used to treat depression, but usually clinical trials will not enroll pregnant or lactating women.Therefore, these drugs are also risky in clinical use.So, if there is a drug that directly targets postpartum depression, it is very helpful for the new mother who suffers from it.
Sage Therapeutics, Inc., USA, specializes in the development of new drugs for central nervous system diseases and has an intravenous drug delivery program, Brexanolone, for the treatment of postpartum depression.Brexanolone is an allosteric modulator that acts on both synaptic and extrasynaptic GABAA receptors.Allosteric modulation of neurotransmitter receptor activity can produce various degrees of desired activity, rather than complete activation or complete inhibition.
The product was granted Breakthrough Therapy by the FDA as early as September 2016.The new drug marketing application submitted by Sage to the US FDA in April 2018 was overwhelmingly approved by two US FDA advisory committees in November of the same year to support its marketing. However, it is necessary to submit a separate Risk Evaluation and Mitigation Strategies including safety and security measures.Sage quickly submitted the plan, but the FDA needed more time to review the plan, so the PDUFA date was postponed from December 19, 2018 to March 19, 2019.Will this be a late 38 holiday gift for new moms?Let's wait and see.
Sexual desire disorder
Food.Color, sex too.But human instincts can also be difficult.Common sexual dysfunction in men can be treated with VIAGRA.Cialis.Bi Li Jin and other well-known drugs to promote blood circulation, improve sexual function.Women are different.The most common female sexual dysfunction is sexual desire disorder, which is the absence of sexual fantasies and sexual desire.It is a psychiatric disorder with an incidence of about 10%.
In August 2015, the US FDA approved Addyi flibanserin for the treatment of widespread sexual desire disorder in premenopausal women.For a time, Addyi was also known as "Viagra Female" or "Wei Jie."The product was originally Boehringer Ingelheim's near-final project.Sprout won approval in 2012 for a $1 billion deal just two months after taking over.However, Addyi is a naturally defective drug that has a slow onset of action and even requires several weeks of daily dosing, clearly not meeting actual needs.Plus vertigo.Low blood pressure.Coma and somnolence and other adverse reactions, and can not be taken with alcohol, not at all by the market.It was supposed to be a big sale, but the sales were actually poor.Even the sales team was disbanded.
That's why the next Viagra for women is all the more exciting.The PDUFA date of Bremelanotide of Palatin, Inc. (USA) was March 23, 2019.This is a pioneering melanocortin 4 receptor agonist with a novel mechanism of action that activates endogenous melanocortin pathways in the brain involved in normal sexual desire and arousal responses to sexual desire in humans.The proposed formulation is a prefilled disposable autoinjector that is self-injected subcutaneously by female patients and is less romantic than the oral formulation.In February 2017, Palatin transferred North American interests to AMAG, and in September of the same year, China (including the mainland.Taiwan.Hong Kong.Macao) equity transfer to Fosun Pharma, and Korea equity transfer to Kwang Dong in November.
People may still be looking forward to oral dosage forms more than injections, which are much more convenient after all, without the pain of a shot.Lorexys from S1 Biopharmaceuticals, USA is an oral combination containing two antidepressants, bupropion and trazodone.S1 is designed to make dopamine.Serotonin and norepinephrine balance, and these are the three neurotransmitters that regulate sexual inhibition and arousal in humans.Phase 2b clinical trials are currently being advanced and a subsequent marketing application will be filed via the 505 (b) (2) route.
Although life is a miraculous process, it is not always expected to be new, especially if both men and women agree.In the past, however, the right to decide whether to use condoms was more in the hands of men.Considering the sense of use.Access or fertility purposes, even with condoms, women often have no way to prevent the ongoing pregnancy consequences of sex.The birth of the pill for women to provide more options, do not have to worry about whether men would like to use, women own initiative.
Over the past half century, humans have invented many kinds of birth control pills.In addition to the common oral tablets, there are injections.Implanting agent.Vaginal ring.Contraceptive stickers, etc.Women can choose their own appropriate contraceptive method according to their life preferences.
Kyleena, a new long-acting intrauterine device developed by German pharmaceutical giant Bayer, was approved by US FDA and EU EMA in 2016.Kyleena is a new low-dose levonorgestrel-releasing intrauterine system (LNG-IUS) that can be removed at any time, and women can quickly return to normal fertility after removal.Kyleena is a small.Flexible.A plastic T-shaped device containing 19.5 mg of the synthetic hormone levonorgestrel.Kyleena is 28 mm x 30 mm in size and 3.8 mm in diameter.Once placed in the womb, Kyleena delivers a sustained release of low doses of levonorgestrel, providing up to 5 years of contraceptive effectiveness.
For Agile, December 2017 was originally the harvest season, however, a complete response from the US FDA is awaiting.In the reply letter, it was pointed out that the Twirla adhesion test method developed by Agile Corporation for low-dose hormonal combination contraceptive patch was defective, and that there was doubt about the relationship between the observation items found in the audit on the third-party manufacturer Corium and the results of clinical trials on in vivo adhesive desire.After discussion with FDA's Orthopedic Advisory Committee on Reproductive and Urological Drugs, the company decided to conduct a non-inferiority study on adhesion with another marketed contraceptive patch product, Xulane. It is expected to complete the trial in the first quarter of 2019 and submit the marketing application again in the first half of this year.Twirla uses Agile's proprietary Skinfusion technology to deliver ethinyl estradiol and levonorgestrel over seven days.The product is applied once a week for three weeks, and no patch is needed for another week, which can improve the compliance of users.
Annovera is a vaginal contraceptive ring shaped like a soft silicone rubber ring with a diameter of about 5.715 centimeters and contains a combination of seconorgestrel acetate and ethinyl estradiol.Place in vagina during use: Place for 21 days.Explanted for 7 days and can use contraception for 28 days.During placement, the hormones contained in ANNOVERA are released through the ring wall at a rate that is absorbed by the vaginal mucosa and exerts a contraceptive effect.Women may place and remove each Annovera by themselves for 1 year.The product was approved by FDA in August 2018.
In addition to the most common hormonal contraceptives, there are some non-hormonal products that have been approved or are being tried for.
Ulipristal is a selective progesterone receptor modulator with antagonistic and partial agonistic effects on progesterone receptors.It binds to progesterone receptors in the human body and thus prevents progesterone from binding to progesterone receptors.In 2009 and 2010, it was approved by the European Union EMA and the US FDA for use in emergency contraception with unprotected intercourse or contraceptive failure within 120 hours (5 days).Another 5 mg strength is approved for the treatment of uterine fibroids.
Amphora, developed by Evofem USA, is a multifunctional vaginal pH regulator that contains L-lactic acid.Citric acid and potassium bitartrate.Developed as a gel that adjusts vaginal pH to a normal range of 3.5 to 4.5, the company maintains an acidic environment that protects against sperm and viral and bacterial pathogens, but not against healthy flora.As early as 2015, the company submitted a new drug marketing application, but in April 2016 received a complete reply letter from the US FDA, pointing out that there are differences in the cohort study in the United States and Russia.If successful, the company plans to submit a new drug application in the second quarter of 2019, after the trial is resumed.It is also being developed for use in gynecologic conditions such as bacterial vaginosis and gonorrhea.
In addition to drugs, there are also devices.Femasys develops a female permanent contraceptive system called FemBloc that does not require anesthesia or implants.This is actually a biopolymer that allows the body itself to initiate wound repair in the fallopian tube to form scar tissue and permanently close the fallopian tube.In early human trials, no significant adverse effects were observed and a 500-subject pivotal trial has been initiated and 100 subjects have been completed.
Menopausal aunt is not a good one
The onset of menstruation means that women begin to develop and gradually become fertile with all kinds of distress.Menopause, on the other hand, means the end of the female reproductive period.Although menstruation fading is a natural physiological phenomenon, but it can also bring a lot of discomfort to women, affecting the quality of life.These symptoms include hot flashes with night sweats.Sleep disturbance.Joint pain and genitourinary symptoms, including low libido.Dyspareunia and bladder incontinence.The main cause of these symptoms is changes in estrogen levels, and the cause is aging of the ovaries.About 85% of postmenopausal women experience at least one symptom of menopause.This is what is often called menopause.
Menopause can lead to moderate to severe vasomotor symptoms, which are commonly referred to as menopausal symptoms in menopausal women due to decreased levels of their own hormones, usually manifested as hot flashes and night sweats.As the ovaries stop producing hormones, circulating estrogen levels fall, often triggering vasomotor symptoms, as well as sleep and mood disorders and genitourinary problems.Hot flashes (including night sweats) are the most common symptom, affecting 80% of women, and can be debilitating and persist for years after menopause.
Since it is a symptom of a drop in hormone levels, it is a good idea to take hormones directly.Pfizer's Duavee (estrogen and bazedoxifene conjugate) was approved by the U.S. FDA in October 2013.In October 2018, the U.S. Food and Drug Administration approved Bijuva from Therapeutics MD, a compound capsule composed of 1 mg estradiol and 100 mg progesterone.This is the first FDA-approved bio-identical combination hormone replacement therapy that is molecularly identical to the hormones produced in women.
However, the use of hormone replacement therapy may cause adverse effects.For example, the most common adverse reactions (≥ 3%) of Bijuva include breast tenderness.Headache.Vaginal bleeding.Vaginal discharge and pelvic pain.Non-hormonal therapies that have been approved for marketing include Noven Pharmaceuticals' Brisdelle (7.5 mg low dose paroxetine mesylate) in July 2013, while strengths such as 10 mg are approved for the treatment of depression.
Fervent Pharmaceuticals is developing a non-hormonal therapy that is not a new compound, but rather an active ingredient with a well-recognized safety profile from numerous older drugs, namely dextromethorphan hydrobromide.The project FP-101 has completed Phase 2A clinical trials and will eventually be marketed via the 505 (b) (2) route.
KNDy neurons increase estrogen synthesis in the ovary and play a role in thermoregulation.When the ovaries fail to synthesize enough estrogen during menopause, KNDy neurons release more signals.These signals will also affect female thermoregulation, which in turn is due to the occurrence of hot flashes.The NK3 receptor antagonist Fezolinetant, developed by Belgian company Ogeda, can reduce the regulatory activity of KNDy by directly acting on neurons.The company was acquired by Astellas in 2017.Currently, fezolinetant has completed a phase 2b clinical trial in which all four endpoints are met in most cohorts.Phase 3 clinical trials are currently being prepared.
KaNDy, UK, has completed a third round of funding and received £25 million for the NT-814 clinical trial.The product acts on both NK1 and NK3 receptors and is used to ameliorate conditions including hot flashes.Multiple menopausal symptoms including sleep and mood problems.Phase 2b clinical trials are currently ongoing and preliminary data are expected to be available by the end of 2019.
It should be said that pharmaceutical companies pay more attention to this disease. In fact, there are still many previously approved drugs, which are not listed here.
Menopausal genitourinary syndrome
Also known as vulvovaginal atrophy (VVA), is a common chronic progressive condition caused by decreased vaginal tissue estrogen, symptoms include vaginal dryness.Irritation.Itching.Pain.Burn.Frequent urination, urgency and dyspareunia.The condition is likely to appear at any stage of a woman's life, but it is more common after menopause, where the incidence is about 50%, of which 50% -60% of patients do not choose to see a doctor, and only 25% of patients will receive appropriate treatment.Vulvovaginal atrophy due to menopause and physiology.Histologically and anatomically related and therefore associated with vasomotor symptoms (flushing.The difference is that vulvovaginal atrophy does not resolve without therapeutic intervention.
However, since vasomotor symptoms, like those of vasomotor symptoms, are caused by a drop in hormone levels, it is also a good idea to take hormones directly.In May 2018, the U.S. FDA approved TherapeuticsMD's Imvexxy, an estradiol vaginal insert for the treatment of moderate to severe dyspareunia, one of the symptoms of vulvovaginal atrophy caused by menopause.
Prasterone (dehydroisoandrosterone, DHEA) is mainly produced by the adrenal cortex and ovaries and is an important precursor of extragonadal hormones in postmenopausal women.DHEA and its sulfates are converted to estrone or testosterone, which is then incorporated into extragonadal tissues (e.g., the brain.Bone and fat) evolve to estradiol or dihydrotestosterone.In November 2016, the US FDA approved Endoceutics' Intrarosa, a prasterone vaginal insert for the treatment of moderate to severe dyspareunia due to vulvovaginal atrophy caused by decreased estrogen levels during menopause.
Ospemifene tablets (Ospemifene) were developed by the Japanese company, Yasano, and are available in the United States (Osphena, February 2013.January 2019) and the European Union (Senshio, January 2015) approved for the treatment of symptoms of vulvovaginal atrophy due to menopause, including moderate to severe dyspareunia and moderate to severe vaginal dryness.The North American market was later bought by Duchesnay.
Osteoporosis is a bone disease in which bone strength is significantly reduced, with the consequence of an increased risk of fracture.According to WHO, 30% of women over the age of 50 suffer from osteoporosis worldwide.The main cause of osteoporosis in elderly women is the absence of estrogen after menopause.The incidence of osteoporosis in the elderly in China is about 15.7%, and the male to female ratio is about 1.0:1.61.
Drugs currently marketed for the treatment of osteoporosis fall into four main classes: 1) antiresorptive, ie, bisphosphonates that inhibit osteoblasts, such as Zoledronic acid from Novartis.2) Selective estrogen receptor modulators, such as raloxifene from Lilly, and Pfizer's Duavee (estrogen and bazedoxifene conjugate) as previously mentioned.3) Bone synthesizing parathyroid hormone analogues such as Lilly's teriparatide.And 4) Monoclonal antibody drugs, such as Amgen's RANKL receptor agonist denosumab.
The current research and development focus is also on the latter two types of drugs.For example, Abaloparatide, which was approved by the US FDA in April 2017, is also a parathyroid hormone-related protein [PTHrP (1-34)] analog that binds to parathyroid receptor 1, thereby regulating metabolism and promoting bone formation.Abaloparatide was originally developed by Ipsen and later transferred to Radius Health.
Romosozumab, developed by Amgen in conjunction with UCB, is a monoclonal antibody that targets the bone formation signaling pathway and inhibits the activity of sclerostin, thereby accelerating bone formation and reducing bone resorption.This product has been approved for marketing by PMDA in Japan on January 8, 2019.Although the US Food and Drug Administration (FDA) declined to approve its launch in 2017, Amgen and UCB have resubmitted their applications for the study.January 16, 2019 announced that the FDA's Advisory Committee on Reproductive and Urological Drugs in Orthopaedics voted overwhelmingly to support the launch of the product.The EU EMA is also under review.Amgen's position in the field of osteoporosis has been further consolidated as the product has been approved for marketing in major countries.
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Vaginal candidiasis of the vulva
Candida vaginitis or vulvovaginal candidiasis, most of which are caused by Candida albicans.About 70% -79% of adult women will experience at least one episode in their lifetime and 50% will relapse.Recurrent vulvovaginal candidiasis (RVVC), which affects about 5 to 8 percent of women, occurs three or more times a year.Most of the disease occurs in women of childbearing age, in the last trimester of pregnancy is also more common, and to reduce after menopause.
Ibrexafungerp is a structurally unique glucan synthase inhibitor recognized by WHO as a novel class of triterpenoid antifungal agents.Originally developed jointly by Scynexis and Merck, the product was abandoned by Merck and continued to be developed by Scynexis for the treatment and prevention of various fungal infections.Current clinical trials for vulvovaginal candidiasis are in phase 3 and a marketing application is planned for 2020.
VT-1161 from Mycovia, Inc., a fungal CYP51 inhibitor that blocks the production of ergosterol, an important component of fungal membranes, is currently in phase 3 clinical trials and is expected to be completed in the second half of 2020.
Bacterial vaginosis is the most common cause of vaginitis, with a recurrence rate of about 20% to 40% after one month of treatment.This is also the most common cause of vaginal discharge in women of childbearing age, accounting for 40% -50% of all cases.The onset of bacterial vaginosis is associated with changes in the normal vaginal flora, such as a change from lactic acid bacteria to a variety of bacteria including facultative anaerobes, the production of volatile amines by new colonies, and a rise in vaginal pH above 4.5 (normal range 4.0-4.5).
Secnidazole from Symbiomix, USA is a potent 5-nitroimidazole antibiotic approved by the US FDA in September 2017 for the treatment of bacterial vaginosis in adult women.This is the only single-dose oral therapy for bacterial vaginosis.
(p) Amphora gel, developed by Evofem, is a multifunctional vaginal pH regulator that adjusts vaginal pH to within normal limits.In addition to protecting against sperm, it can also eliminate bacterial pathogens.It is also being developed for bacterial vaginosis.
VivaGel BV, developed by Starpharma, USA, is a non-antibiotic aqueous vaginal gel for the treatment of bacterial vaginosis and prevention of recurrent bacterial vaginosis.The product has been approved in Europe and Australia, but in December 2018 the US Food and Drug Administration said more clinical data were needed.
All five antibacterial drugs have obtained FDA's QIDP certification.
What is the real lair?
This is a relatively common, benign tumor of uterine smooth muscle proliferation that occurs in women of childbearing age, with an incidence of 20% to 40%. The risk increases with age and peaks at menopause.Some uterine fibroids have no symptoms, so they won't be diagnosed.Uterine fibroids usually cause menstrual pain.Non-menstrual vaginal bleeding.Infertility.Anemia, etc.In addition, the most common treatment for symptomatic uterine fibroids is hysterectomy.
The aforementioned 30 mg strength of ulipristal has been approved by the European Union EMA and the US FDA for emergency contraception.Ulipristal acts as a selective progesterone receptor modulator that acts directly on three target tissues, the endometrium.Progesterone receptors in uterine fibroids and the pituitary gland. The compound is also approved by the European Union's EMA for the treatment of uterine fibroids at a dose of 5 mg.However, since several patients had severe liver injury due to medication, the EMA Pharmacovigilance Risk Assessment Committee, after careful investigation, recommended that its medication be restricted and that measures be taken to reduce the risk of liver injury with the drug, including contraindication in patients with known liver problems, liver function tests before, during and after treatment, and informing patients about the risk of liver injury.Because of the above safety concerns, although the application for marketing of the treatment of uterine fibroids in patients with abnormal uterine bleeding symptoms was selected, it was still rejected by the US FDA in August 2018.
Relugolix developed by Takeda was approved by PMDA in Japan on January 8, 2019 for the treatment and symptom relief of uterine fibroids, including menorrhagia.Lower abdominal pain.Low back pain and anemia.Relugolix is a gonadotropin-releasing hormone (GnRH) receptor antagonist that rapidly reduces estrogen and progesterone in women.It should be noted that the rights and interests of this product in Japan and specific Asian countries belong to Myovant.Myovant has conducted two phase 3 clinical trials worldwide for the treatment of menorrhagia associated with uterine fibroids and pain associated with endometriosis.
The Swiss company ObsEva, which is also committed to female reproductive health mentioned above, also has a GnRH receptor antagonist, Linzagolix, which is currently undergoing phase 3 clinical trials on uterine fibroid-related menorrhagia and has completed phase 2b clinical trials on endometriosis-related pain.
Endometrial cells are supposed to grow in the uterine cavity, but because the uterine cavity passes through the fallopian tubes and ovaries.The pelvis communicates, thus allowing the endometrial cells to enter the ovary via the fallopian tube.Endometriosis develops when the pelvis and adjacent areas of the uterus grow ectopically.The incidence of this condition in women of childbearing age is about 10% -15%.Seventy percent of these patients have chronic pelvic pain.30% - 50% of patients will cause infertility.In addition, women with endometriosis have a 30% to 66% increased risk of developing ovarian cancer.Endometriosis is diagnosed over a long period of time, taking an average of 7.5 years from symptom onset to diagnosis.
On July 23, 2018, the US FDA approved Elagolix for the treatment of pain due to endometriosis.Elagolix is an oral GnRH antagonist that ultimately lowers circulating gonadal hormone levels by inhibiting pituitary gonadotropin-releasing hormone receptors.In addition, phase 3 clinical trials of this product in the treatment of uterine fibroids are also ongoing.
Cancer, The Emperor of Disease
Worldwide, breast cancer is the most common cancer in women, with more than 2 million new cases in 2018.The incidence rate of female breast cancer in China ranks 160th among 184 countries, and the mortality rate ranks 177th, which is at the global low level.However, due to the large population base in China, the incidence and death of female breast cancer accounted for 11.2% and 9.2% of the global incidence and death, respectively, ranking among the top in the world.
Female breast cancer ranks first and fifth in the incidence and mortality of female malignancies in China, respectively.The data released in 2018 is about 278,900 cases, accounting for 16.51% of female malignant tumor incidence.The data released in 2019 is about 304,000 new cases, accounting for 17.10% of female malignant tumors, showing an upward trend.
In recent years, the US FDA has approved a number of breast cancer targeted drugs, such as Pfizer's PARP inhibitor Talazoparib and three CDK4/6 inhibitors, Pfizer's Palbociclib, Novartis' Ribociclib and Lilly's Abemaciclib, and earlier Roche's continually upgraded product, Trastuzumab (Herceptin). Pertuzumab (Perjeta) and Trastuzumab-Metanaxine Conjugate (Kadcyla).However, in January 2018, MacroGenics' Margetuximab was granted fast-track qualification by the US FDA. For patients with metastatic HER2 breast cancer who have failed to respond to trastuzumab and pertuzumab, the pivotal phase 3 clinical trial of this drug has reached the primary endpoint. It is expected to submit a marketing application to the FDA in 2019.The Chinese rights and interests of this product have been reinstated.
In addition, there are three Phase 3 clinical trials of new drugs for breast cancer that are of most interest: Trastuzumab-Deruxtecan.Alpelisib and Ipatasertib.
These drugs are essentially used in HER2-positive breast cancer.Triple-negative breast cancer, which accounts for 12% -20% of breast cancers, has been expecting breakthroughs in treatment.
Originally in January 2019, Immunomedics' antibody drug conjugate, sacituzumab govitecan, is expected to be approved by the US FDA for the treatment of metastatic triple-negative breast cancer (mTNBC), but a complete response letter was received.The defect is not the clinical efficacy or safety, but the reason of CMC pharmacy.Sacituzumab govitecan is a humanized IgG1 antibody targeting the TROP-2 antigen conjugated to SN-38, the metabolically active product of the chemotherapeutic drug irinotecan, a topoisomerase I inhibitor.TROP-2 is a cell surface glycoprotein expressed in more than 90% of TNBC.This product has been granted breakthrough therapy by the US FDA.
It is worth mentioning that Roche PD-L1 product Tecentriq in combination with albumin paclitaxel (Abraxane) for the first-line treatment of PD-L1 positive locally advanced or metastatic TNBC has also received the priority review from the FDA, PDUFA on March 12, 2019.If approved, the combination of TECENTRIQ with ABRAXANE will be the first cancer immunotherapy regimen for the treatment of PD-L1 positive metastatic TNBC.
Nearly 300,000 new cases of ovarian cancer are diagnosed each year worldwide, with more than 150,000 deaths.Ovarian cancer is the tenth leading cause of female cancer deaths in China, but there is no ovarian cancer in the top ten.Although the incidence of ovarian cancer in China is relatively low, the huge population base still makes the burden of ovarian cancer in China huge.In 2015, there were about 52100 new cases and 22500 deaths in China.This compares with 21,290 and 14,180 in the United States, respectively.These figures show the extent of the cancer.
Three PARP inhibitors have been approved by the US Food and Drug Administration for the treatment of ovarian cancer in recent years.Rucaparib from Clovis and Niraparib from Tesaro, the last of which is the first PARP inhibitor not to be tested for BRCA or other biomarkers prior to dosing.In addition, there is Roche's bevacizumab (Avastin).The Chinese interest in niraparib, including Hong Kong, has been re-approved and approved in Hong Kong in October 2018, while the listing application in China in January 2019 has been accepted and granted priority review.
On March 1, 2019, ImmunoGen announced that the Phase III clinical trial of Mirvetuximab Soravtansin failed to reach the primary endpoint: progression-free survival. Mirvetuximab Soravtansine is an antibody-conjugated drug (ADC) that targets FRα (folate receptor alpha). It combines a humanized monoclonal antibody that binds to FRα and a small molecule capable of producing cytotoxicity through a disulfide bond, and belongs to the world's first-in-class of the FRα target in the ADC field. FRα is a kind of Over-expressed proteins in ovarian cancer are expressed at a high level in most (80-96%) epithelial ovarian cancer, but not in normal ovarian epithelium, and should be an ideal target for the treatment of ovarian cancer. However, in 2013 Eisai's farletuzumab also collapsed in three clinical trials, again because the primary endpoint of progression-free survival was not met.
Endometrial cancer ranks fifth among female cancer patients worldwide and third in Western countries.In China, the incidence of female cancer is in the 9th place, and the proportion has an upward trend, but the death rate ranks in the 10th place.Endometrial cancer is completely curable and the mainstay of treatment is hysterectomy.More than 80% of patients survive more than 5 years.
However, few drugs are indicated for endometrial cancer.In addition to the approval of megestrol acetate for adjuvant therapy decades ago, only in May 2017, the US FDA approved the use of Pabolizumab (Keytruda) in patients with unresectable or metastatic solid tumors with microsatellite instability or mismatch repair deficiency.In August 2018, Pabolizumab in combination with Lenvatinib received FDA Breakthrough Therapy designation for the treatment of advanced or metastatic non-microsatellite unstable high or mismatch repair intact endometrial cancer.
Checkpoint Therapeutics, Inc. also has a PD-L1 monoclonal antibody, CK-301, and announced in January 2019 that the ongoing multicenter clinical trial of CK-301 has entered the cohort expansion phase and started enrolling patients with microsatellite unstable high or microsatellite stable endometrial cancer.Preliminary data showed that CK-301 was safe and well tolerated at the specified dose, and treatment-related adverse events were consistent with those of commercially available PD-1/PD-L1 antibody.
Worldwide, cervical cancer ranks fourth among female cancers, with more than 500,000 new cases in 2018.In China, cervical cancer ranks sixth in female cancer incidence and eighth in mortality.Cervical cancer is mainly caused by human papilloma virus (HPV) infection.Merck's nine-valent cervical cancer vaccine protects 90 percent of cervical cancers caused by HPV.Although China has approved the import and marketing of the 9-valent cervical cancer vaccine from Merck with extremely high efficiency, it is still difficult to obtain a dose today due to the fact that the production capacity is seriously unable to keep up with the huge domestic demand (see: year-end inventory: the top ten hot words in the pharmaceutical circle in 2018).
In addition to eagerly hoping for more and better cervical cancer vaccines, people also hope to have therapeutic products.AXAL (AXALIMOGENE FILOLISBAC), developed by Advaxis, USA, is an immunotherapy targeting Listeria monocytogenes (Lm), which genetically modifies the attenuated active Listeria to produce anticancer T cells against cancer antigens while destroying the natural defense of tumor microenvironmental protection immune attack and attacking HPV-related cancers.This project was granted fast track qualification and orphan drug certification by the US FDA.This highly anticipated project has experienced a twist.It was first halted by the FDA in March 2018 due to the death of a subject in a Phase 1/2 trial with AstraZeneca's IMFINZI.In January 2019, the FDA suspended enrollment of patients in Phase 3 clinical trials due to issues related to pharmaceutical research (CMC).Then, let's pray in silence.
Maybe if you read this, you're still wondering.Since thalidomide has been shown to be harmful to the fetus and cannot be used, is it impossible for pregnant women to face the painful morning sickness?Of course not, except for vitamins.In addition to acupressure and acupuncture, life habits pay attention to eating small meals.High carbon water.In addition to measures such as low fat and proper intake of ginger products, in April 2013, the US FDA approved Duchesnay's Diclegis (doxylamine + vitamin B6) specifically for the treatment of nausea and vomiting during pregnancy.
In fact, as early as 1956, the US FDA approved a three-in-one drug containing dicyclomine + doxylamine + vitamin B6, trade name Bendectin.Since dicyclomine was found to be of no benefit, it was changed to doxylamine + vitamin B6 as a two-in-one drug in 1976.From the late 1960s and through the 1970s, a lot of research reports have questioned the safety of the product, especially the suspicion of causing birth defects.Law firms have launched a propaganda campaign that has led to hundreds of lawsuits against producers, as the haze from the "stop-reaction" affair has long failed to dissipate, creating a huge shadow in the hearts of Americans and leading media reports.Eventually, manufacturers were unable to cope, and in 1983 announced the withdrawal of the product, for which no drug in the US market was specifically designed to treat morning sickness.However, epidemiological studies have found that hospital admissions for emesis have doubled over the years since the product was withdrawn from the market, but birth defects have remained largely stable.
After 30 years, the U.S. FDA's approval of Diclegis was based on a random.Safety and efficacy data from placebo-controlled clinical trials have also considered extensive data on the non-teratogenic effects of the combination of doxylamine and vitamin B6, but the FDA will continue to carefully monitor the post-marketing use of Diclegis.
She deserves more care
The above 20 diseases and symptomatic drugs are only briefly listed, but it is actually easy to find that there are so many diseases that may rage her around you.Maybe now you can understand more deeply that her pain is unspeakable, and at the same time you know more:
She deserves more care!
Special statement: This article is not applicable to medical consultation.If you have any questions, please consult a regular medical institution.