New Options Are Emerging in the Search for Better Birth Control
A decade ago, Elizabeth Summers' options for birth control suddenly narrowed. Doctors diagnosed her with Factor V Leiden, a rare genetic disorder, after discovering blood clots in her lungs. The condition increases the risk of clotting, so physicians told Summers to stay away from the pill and other hormone-laden contraceptives. "Modern medicine has generally failed to provide me with an effective and convenient option," she says.
But new birth control options are emerging for women like Summers. These alternatives promise to provide more choices to women who can't ingest hormones or don't want to suffer their unpleasant side effects.
These new products have their own pros and cons. Still, doctors are welcoming new contraceptives following a long drought in innovation. "It's been a long time since we've had something new in the world of contraception," says Heather Irobunda, an obstetrician and gynecologist at NYC Health and Hospitals.
On social media, Irobunda often fields questions about one of these new options, a lubricating gel called Phexxi. San Diego-based Evofem, the company behind Phexxi, has been advertising the product on Hulu and Instagram after the gel was approved by the Food and Drug Administration in May 2020. The company's trendy ads target women who feel like condoms diminish the mood, but who also don't want to mess with an IUD or hormones.
Here's how it works: Phexxi is inserted via a tampon-like device up to an hour before sex. The gel regulates vaginal pH — essentially, the acidity levels — in a range that's inhospitable to sperm. It sounds a lot like spermicide, which is also placed in the vagina prior to sex to prevent pregnancy. But spermicide can damage the vagina's cell walls, which can increase the risk of contracting sexually transmitted diseases.
"Not only is innovation needed, but women want a non-hormonal option."
Phexxi isn't without side effects either. The most common one is vaginal burning, according to a late-stage trial. It's also possible to develop a urinary tract infection while using the product. That same study found that during typical use, Phexxi is about 86 percent effective at preventing pregnancy. The efficacy rate is comparable to condoms but lower than birth control pills (91 percent) and significantly lower than an IUD (99 percent).
Phexxi – which comes in a pack of 12 – represents a tiny but growing part of the birth control market. Pharmacies dispensed more than 14,800 packs from April through June this year, a 65 percent increase over the previous quarter, according to data from Evofem.
"We've been able to demonstrate that not only is innovation needed, but women want a non-hormonal option," says Saundra Pelletier, Evofem's CEO.
Beyond contraception, the company is carrying out late-stage tests to gauge Phexxi's effectiveness at preventing the sexually transmitted infections chlamydia and gonorrhea.
Phexxi is inserted via a tampon-like device up to an hour before sex.
Phexxi
A New Pill
The first birth control pill arrived in 1960, combining the hormones estrogen and progestin to stop sperm from joining with an egg, giving women control over their fertility. Subsequent formulations sought to ease side effects, by way of lower amounts of estrogen. But some women still experience headaches and nausea – or more serious complications like blood clots. On social media, women recently noted that birth control pills are much more likely to cause blood clots than Johnson & Johnson's COVID-19 vaccine that was briefly paused to evaluate the risk of clots in women under age 50. What will it take, they wondered, for safer birth control?
Mithra Pharmaceuticals of Belgium sought to create a gentler pill. In April, the FDA approved Mithra's Nextstellis, which includes a naturally occurring estrogen, the first new estrogen in the U.S. in 50 years. Nextstellis selectively acts on tissues lining the uterus, while other birth control pills have a broader target.
A Phase 3 trial showed a 98 percent efficacy rate. Andrew London, an obstetrician and gynecologist, who practices at several Maryland hospitals, says the results are in line with some other birth control pills. But, he added, early studies indicate that Nextstellis has a lower risk of blood clotting, along with other potential benefits, which additional clinical testing must confirm.
"It's not going to be worse than any other pill. We're hoping it's going to be significantly better," says London.
The estrogen in Nexstellis, called estetrol, was skipped over by the pharmaceutical industry after its discovery in the 1960s. Estetrol circulates between the mother and fetus during pregnancy. Decades later, researchers took a new look, after figuring out how to synthesize estetrol in a lab, as well as produce estetrol from plants.
"That allowed us to really start to investigate the properties and do all this stuff you have to do for any new drug," says Michele Gordon, vice president of marketing in women's health at Mayne Pharma, which licensed Nextstellis.
Bonnie Douglas, who followed the development of Nextstellis as part of a search for better birth control, recently switched to the product. "So far, it's much more tolerable," says Douglas. Previously, the Midwesterner was so desperate to find a contraceptive with fewer side effects that she turned to an online pharmacy to obtain a different birth control pill that had been approved in Canada but not in the U.S.
Contraceptive Access
Even if a contraceptive lands FDA approval, access poses a barrier. Getting insurers to cover new contraceptives can be difficult. For the uninsured, state and federal programs can help, and companies should keep prices in a reasonable range, while offering assistance programs. So says Kelly Blanchard, president of the nonprofit Ibis Reproductive Health. "For innovation to have impact, you want to reach as many folks as possible," she says.
In addition, companies developing new contraceptives have struggled to attract venture capital. That's changing, though.
In 2015, Sabrina Johnson founded DARÉ Bioscience around the idea of women's health. She estimated the company would be fully funded in six months, based on her track record in biotech and the demand for novel products.
But it's been difficult to get male investors interested in backing new contraceptives. It took Johnson two and a half years to raise the needed funds, via a reverse merger that took the company public. "There was so much education that was necessary," Johnson says, adding: "The landscape has changed considerably."
Johnson says she would like to think DARÉ had something to do with the shift, along with companies like Organon, a spinout of pharma company Merck that's focused on reproductive health. In surveying the fertility landscape, DARÉ saw limited non-hormonal options. On-demand options – like condoms – can detract from the moment. Copper IUDs must be inserted by a doctor and removed if a woman wants to return to fertility, and this method can have onerous side effects.
So, DARÉ created Ovaprene, a hormone-free device that's designed to be inserted into the vagina monthly by the user. The mesh product acts as a barrier, while releasing a chemical that immobilizes sperm. In an early study, the company reported that Ovaprene prevented almost all sperm from entering the cervical canal. The results, DARÉ believes, indicate high efficacy.
A late-stage study, slated to kick off next year, will be the true judge. Should Ovaprene eventually win regulatory approval, drug giant Bayer will handle commercializing the device.
Other new forms of birth control in development are further out, and that's assuming they perform well in clinical trials. Among them: a once-a-month birth control pill, along with a male version of the birth control pill. The latter is often brought up among women who say it's high time that men take a more proactive role in birth control.
For Summers, her search for a safe and convenient birth control continues. She tried Phexxi, which caused irritation. Still, she's excited that a non-hormonal option now exists. "I'm sure it will work for others," she says.
One of the main factors that will influence the ultimate trajectory of the novel coronavirus pandemic will be the availability of a vaccine.
Vaccine development has traditionally been a process measured in years and even decades.
Vaccines are incontrovertibly the best means to control infectious diseases and there are no human vaccines against any of the (now) 7 known human coronaviruses. As soon as the gravity of this outbreak was recognized, several companies, along with governmental and non-governmental partners, have embarked on a rapid development program to develop a vaccine targeted at this virus.
Vaccine development has traditionally been a process measured in years and even decades as scientists tinker with a pathogen trying to weaken or dissemble it to render it capable of creating an effective immune response with acceptable levels of side effects. However, in 2020, powerful new vaccine technologies are available to augment traditional vaccine development and are responsible for the rapid delivery of a vaccine candidate for the start of clinical trials.
Vaccine Platforms: A Game-Changing Technology
The new technologies that are being harnessed are what are known as vaccine platform technologies. Vaccine platforms, as my colleagues and I wrote in a report assessing their promise, offer a means to use the same building blocks to make more than one vaccine. To slightly oversimply, a vaccine platform confers the ability to switch out the pathogen being targeted very rapidly, akin to changing a video game cartridge. Indeed, the recently FDA-licensed Ebola vaccine uses another virus as a platform with the requisite Ebola protein inserted.
Because of this rapid availability to utilize platforms for a variety of different targets, the initial development process can be significantly shortened. This is especially true for vaccines utilizing the genetic material of the target alone. These DNA and RNA vaccines basically can be "printed" once the genetic sequence of the target is known.
An RNA vaccine is the approach being used by the Cambridge-based biotech company Moderna – which took just 42 days to produce an experimental vaccine candidate. Clinical testing is expected to begin next month on 45 healthy volunteers.
Another biotech, the Pennsylvania-based Inovio, is using a DNA approach. In essence, such vaccines involve the genetic material being injected and translated into a viral protein by human cells, which then prompt the immune system to make antibodies.
There are other approaches as well. One company, the Maryland-based Novavax, will use nanoparticles, while another is attempting to adapt an orally administered avian coronavirus vaccine and Johnson & Johnson is using different virus platforms to deliver coronavirus proteins (similar to their experimental Ebola vaccine).
At this stage, it is important for all approaches to be on the table in the hope that at least one makes it through clinical trials. There also may be a need for different types of vaccines for different populations.
Vaccines Will Still Take Time
Despite the quick development time made possible by the use of vaccine platforms, clinical testing for safety, efficacy, and dosing schedules will still take months to complete. After this process, the vaccine will need to be mass produced in large quantities to vaccinate, basically, the world. So, for all intents and purposes, we cannot expect to see an approved vaccine for at least a year or maybe longer if everything does not go perfectly well in clinical trials.
Vaccine platform technologies offer a bright ray of hope in the bleak shadow of the pandemic.
Once a vaccine is available, it will likely appear in batches to be distributed to those at highest risk for severe disease, such as the elderly and those with underlying conditions, as well as healthcare workers, first. At this time, it appears children are less likely to experience severe illness and they may not be the first targets for the vaccine but, if this virus is with us (as is predicted), coronavirus vaccination could become part of routine childhood vaccinations.
Changing Pandemic Trajectory
Vaccination will not come fast enough to impact the initial wave of the novel virus which may continue until summer approaches in temperate climates. However, it will be a crucial tool to blunt the impact of a future appearance in the following respiratory virus season. This reappearance is all but assured as this virus has adeptly established itself in human populations and is behaving like the community-acquired coronavirus that it is.
A Glimmer of Hope
When looking at the trajectory of the virus, it can appear, thus far, that no public health effort has made a substantial impact on the spread of the virus. However, that trajectory will change with the advent of an efficacious vaccine. Such a vaccine, especially if conferring protection against other human coronaviruses, may result in coronaviruses being taken off the table of biological threats altogether in the future.
Vaccine platform technologies offer a bright ray of hope in the bleak shadow of the pandemic and, if successful, will change the way the world approaches future pandemic threats with more rapid deployment of platform-based vaccines.
Dr. Adalja is focused on emerging infectious disease, pandemic preparedness, and biosecurity. He has served on US government panels tasked with developing guidelines for the treatment of plague, botulism, and anthrax in mass casualty settings and the system of care for infectious disease emergencies, and as an external advisor to the New York City Health and Hospital Emergency Management Highly Infectious Disease training program, as well as on a FEMA working group on nuclear disaster recovery. Dr. Adalja is an Associate Editor of the journal Health Security. He was a coeditor of the volume Global Catastrophic Biological Risks, a contributing author for the Handbook of Bioterrorism and Disaster Medicine, the Emergency Medicine CorePendium, Clinical Microbiology Made Ridiculously Simple, UpToDate's section on biological terrorism, and a NATO volume on bioterrorism. He has also published in such journals as the New England Journal of Medicine, the Journal of Infectious Diseases, Clinical Infectious Diseases, Emerging Infectious Diseases, and the Annals of Emergency Medicine. He is a board-certified physician in internal medicine, emergency medicine, infectious diseases, and critical care medicine. Follow him on Twitter: @AmeshAA
Medical Tourism Is Booming, Fueled by High Costs and Slow Access
When Bridget Snell found out she had multiple sclerosis, she knew she would put up a fight. The 45 year-old mother of two, who lives in Duxbury, Mass., researched options to slow the progress of the disease. The methods she had been trying were invasive, often with side effects of their own.
An estimated 2.2 million Americans will travel abroad for medical care in 2020.
Then she stumbled upon autologous hematopoietic stem cell transplantation (AHSCT), an experimental and controversial procedure that uses the patient's own stem cells to try to halt the progress of the disease. The FDA has not approved this procedure and last year issued a warning about unapproved stem cell therapies.
Despite the lack of established science, Snell weighed her options and decided she would undergo the procedure at Clinica Ruiz, a private clinic in Puebla, Mexico, which boasts of the largest volume of cases in the world using the procedure to treat MS. In April 2018, she went to Mexico for treatment, returned home in a month, and continues to do well.
But a positive outcome is far from assured, says Sheldon Krimsky, adjunct professor in the Department of Public Health and Community Medicine at the Tufts School of Medicine.
"Often you can't get a good sense of what the quality of treatment is in another country," Krimsky says, adding that many companies promise procedures whose results have not been clinically validated. "Unfortunately, people are very easily persuaded by hope."
Traveling for Medical Care
Snell is one of many Americans who have traveled abroad to access medical care. Patients Beyond Borders, a medical tourism consultancy, estimates that 2.2 million Americans will do so in 2020. A 2018 BCC report projected a five-year compounded annual industry growth rate of 13.2 percent. Adding to the demand is the aging population, which is expected to reach 95 million people by 2060 – nearly double the number in 2018.
While Snell traveled to Mexico to try a procedure that was not yet available in the United States, other patients do so for a variety of reasons, primarily cost and speed of access. For example, despite having "pretty good insurance coverage," Washington resident Soniya Gadgil needed dental procedures that would have cost thousands of dollars out-of-pocket. An India native, she decided to travel to Pune, India to visit her parents -- and while there, she got the two root canals and implant that she needed. Gadgil saved 60 percent on the final bill.
Leaving the country for medical care is not restricted to dental work or FDA-banned procedures either. Patients visit countries around the world — South America, Central America, and the Caribbean top the list — for a number of other problems, such as knee and hip replacements and bariatric operations. The most common procedures sought abroad are for dentistry, cosmetic surgery, and cardiac conditions.
Traveling abroad to access less expensive procedures is a damning indictment of healthcare delivery in the United States, says Dr. Leigh Turner, associate professor at the Center for Bioethics at the University of Minnesota. "We have people who are being forced out of the system because of high costs. Collectively it suggests a real structural problem in terms of the organization of healthcare in the United States," Turner says.
The Growth of the Online Marketplace
Nevertheless, medical tourism is booming and a number of online businesses now meet patients' demand for discovery and facilitation of medical care abroad, like PlanMyMedicalTrip.com, Doctoorum.com, and Wellness Travels.
Anurav Rane, CEO and Founder of PlanMyMedicalTrip.com, says the company presents each potential client with options, a la Expedia. A knee replacement in India costs $2,500, a significantly cheaper option even with a $1,110 round-trip airfare from the United States, Rane says. The average cost for an inpatient total knee replacement in the United States in 2019 was a little more $30,000.
Once the client chooses a specific procedure at a specific hospital, the company facilitates the necessary groundwork including the medical visa, tickets, hotel stay, booking the procedure and pre and post-op stay, and consults with the surgeons or doctors even before arrival. "The hassle of planning is on us," Rane says. Once patients are settled in the accommodations, they undergo the procedure.
Playing in the Legal Shadows
The online marketplace companies and the medical team execute an orchestrated dance – but what happens if the patient is harmed during or after the procedure?
Turner says that medical malpractice, if it occurs, can be difficult to pursue abroad. "There are countries where the courts are notoriously slow and it's very difficult to get any kind of meaningful action and settlements," he says, even if the claims have a legitimate basis.
The industry's biggest challenge is trust.
Snell signed a waiver absolving her surgeons in Mexico of any legal claims. But, she points out, that's standard process even for procedures in the United States. "I signed just as many waivers as I would going into any surgery [in the US]."
While that might well be true, Turner argues, Americans don't waive legal rights when they sign consent forms. "There are some protections for patients here in the United States."
Beyond U.S. Medical Tourism
As expected, it's not just Americans who travel abroad for medical care. Lithuania-based Wellness Travels sees a significant percentage of its clients from the EU. PlanMyMedicaltrip.com has 15,000 surgeons and doctors from 12 countries in its database. Egypt-based Doctoorum works with professionals in its own country and attracts clients from the Middle East. It is looking to expand to include doctors from Jordan and India, among other countries.
The term "tourism" is misleading here because it muddies the picture about what post-op should really look like, says Gediminas Kondrackis of Wellness Travels. "Unfortunately a lot of medical travel facilitators mislead their clients by advertising beach holiday packages and the like. Post-op is really about quiet recovery inside for a few days; being out in the sun is not advisable."
The industry's biggest challenge is trust. "The dentist I went to is actually a friend of mine who has a successful practice for several years," says Gadgil, the Washington resident who had dental work done in India. "I'd hesitate to go to someone I don't know or to a place I have no experience with." Her apprehensions are not unusual. After all, anxiety is an expected reaction to any surgery. Word-of-mouth, cost savings, and thorough research may alleviate some of these trust issues.
"I had natural apprehensions and would have had them had I gone up the road to Brigham and Women's (in Boston) just as I did over the border," Snell says, "but I had done my homework extensively. That took a lot of the fear out of it."
Medical tourism will only increase, predicts Kondrackis. "There is still a lot of room to grow. Higher numbers of medical travelers could help reduce the strain on local healthcare systems by reducing wait times and controlling costs."
While patients who have benefited from medical tourism swear by it, the best cure would be to start at home by establishing healthcare equity, Krimsky says.
On the flip side, says Turner, it is debatable whether medical tourism actually benefits host countries, where local residents might get priced out of procedures at these exclusive clinics. Even if laws in host countries such as India might mandate "charity care" for poorer local patients, that does not always happen, Turner says. The trickle-down theory that these more expensive clinics will broaden access to care is often a pipe dream, he adds.
While patients who have benefited from medical tourism swear by it, the best cure would be to start at home by establishing healthcare equity, Krimsky says. "Now if we had universal healthcare in the United States," he adds, "that would be an entirely different story."
Or maybe not. Rane, of PlanMyMedicalTrip.com, has observed an influx of patients to India from Canada, a country with universal healthcare.
The reason they say they travel for care? Long wait times for procedures.