Oct31

What are we waiting for? Challenges of developing male birth control and MPTs

Thursday, 31 October 2019

Male Contraceptive Initiative (MCI) and the Initiative for Multipurpose Prevention Technologies (IMPT) share similar missions and challenges—as well as some product overlap. Both organizations understand the importance of innovative, impactful products for men, women, their families, and the world.

Male contraceptive products and multipurpose prevention technologies (MPTs) have been declared to be “coming soon” for years. Multiple articles (such as this, this, and this) dating back to the early 2000s have claimed that a male pill is on the way. Just published this month, another piece suggests that scientists have been working on male contraception for “almost half a century.” More recently, the MPT concept grew out of a grassroots initiative in 2009. Ten years later, 31 products are now in the product development pipeline. So why aren’t either of these innovative classes of products available yet?

A survey recently conducted by MCI found that all genders want more male birth control options. A UK-based study compliments MCI’s results in finding that the percentage of sexually active British men who would consider using hormonal contraception is the same percentage as British women who are currently using contraceptive methods. Similarly, 80% of survey respondents said contraception should be a “shared responsibility” between partners. MPTs have long tested well with end-users (in studies such as this, this, and this). Research has shown that the public wants both MPTs and male contraception, and both are potential tools to help men and women live healthy lives.

With anticipation mounting for these products to hit the market, this post focuses on why male contraceptives are still, after all these years, in development. Because of product similarities, the male contraception drug pipeline is relevant for the MPT field as well.

I. THE PROCESS
The drug development process is a long, tedious, expensive ordeal that tries to answer the following questions:

  • What could be a potential way that a contraceptive could work?
  • What pill/device/approach could work as a contraceptive?
  • Does it work in animal testing?
  • Could it be made into an actual pill/shot/implant…?
  • Is it safe, effective, feasible, and reliable?
  • Does it actually work in humans, with minimal adverse effects?

The process for male contraceptive development can be varied and is not often linear, but the below is a representative pathway for some male contraceptive options.

II. DRUG DEVELOPMENT

The Aha! Moment

A researcher in a lab finds some cellular function or defect: some component of reproduction that, when missing, seems to make men infertile. We’ll call this the “target.”

Timeline: This is always happening with lots of different potential methods that different researchers are working on.

But Does It Work?

The researcher tests an animal (often a mouse) whose reproductive system has some characteristics similar to humans’. They want to know if their target can be changed in some way to make the animal infertile, because if it works in the animal, that might mean it will work in people. They might also be testing human sperm samples at this point.

Timeline: Months to many years.
Cost: Tens of thousands.
Methods in this stage: There is a lot of exploration in different labs at this stage, with many researchers exploring leads that they have found.

Target Feasibility

The researcher starts to develop the actual contraceptive that a man will take in the future. In this process, they’re trying to find a way to modify, control, and trigger infertility using their target, in a way that can somehow ultimately be delivered to a person. Can the drug be absorbed in the body? How might it be delivered…in a pill? A shot? A skin patch?

Timeline: Several years.
Cost: Hundreds of thousands.
Methods in this stage: Lots! Some that MCI even funds such as These both affect sperm motility.

Are We Sure?

Lots of testing happens in animals and systems that represent human reproduction to make sure that the drug works in the right way, and is safe and viable as a contraceptive.

Timeline: Several years.
Cost: Hundreds of thousands.
Methods in this stage: HIPK4 (which MCI also funds). This affects the production of sperm.

Is It Safe?

The researcher hones the drug even more to make sure that it’s safe. They also choose the right dosage form, like a pill, a shot, or an implant, and make sure that the dosage, how long it works, and effectiveness are just right. If there are other important features of the drug, like reversibility, that also can be tested here. Ultimately, researchers are ensuring the drug is up to the rigorous US FDA standards for approval.

Timeline: Several years.
Cost: Hundreds of thousands to millions.
Methods in this stage: Eppin (sperm motility) Echo-VR/Adam (blocks vas deferens), VasDeBlock (blocks vas deferens), Vasalgel (blocks vas deferens, funded by MCI), and Adam (blocks vas deferens, funded by MCI).

III. CLINICAL TRIALS

It works! But…does it work in actual people?

If the drug is shown through the above steps to be safe, effective, and have a reliable dosage and dosage form, then the researcher applies for an Investigational New Drug application, allowing the drug to move to human studies. Because they can make so much money on a drug that is later able to be sold, investors and pharma companies sometimes like to come in and invest somewhere in the process below.

Phase I Clinical Trial

This is the first time a researcher tests their drug in real humans. In this stage, they want to see if the contraceptive has side effects at different dosages and how it’s handled by the body. Most drugs move forward from this stage.

Timeline: Months to 2 years.
Cost: 2-5 million.
Methods in this stage: Gendarussa (impacts sperm motility or fertilization) is being tested in the equivalent of this stage in Indonesia, but it won’t be available in the US until it goes through the American process, H 11-beta-mntdc, DMAU.

Phase II Clinical Trial

In this stage, people continue to be tested to see what the side effects are and how safe the contraceptive is. The drug is also tested for how well it works. About a fifth drugs move forward from this stage.

Timeline: Months.
Cost: Between 5-20 million.
Methods in this stage: RISUG (blocks vas deferens) is being tested in the equivalent of this stage in India, but it won’t be available in the US until it goes through the American process, NES-T.

Phase III Clinical Trial

The goal of this stage is to see if the contraceptive actually benefits men and couples, and also shows researchers if there are any long-term or rare side effects, since this time it’s tested on many more people. Testing on a large, diverse group of people provides more information about the effectiveness of the drug. About a third of drugs that make it to phase three move forward.

Timeline: 3-4 years.
Cost: Between 10-50 million.

Then what?

Once a drug makes it through these three phases, it can be approved and then can be marketed.

Phase IV Clinical Trial

“Post-Market Safety Monitoring” happens here. During this period, the safety, side effect profile, and efficacy of the drug is monitored.

Timeline: once drug becomes available, ongoing.

This hasn’t happened with male contraceptives yet! When it does, lots of things have to happen. The new contraceptive will be in the news and will be marketed to consumers. Doctors will have to be trained on how to use it and will have to be motivated to prescribe it to their patients. Insurance will have to cover it. People will have to know it exists and want to use it.

So, why isn’t male birth control available yet? Because it takes a really long time to develop a drug, and because it’s impossible to tell in early stages which drugs are actually going to work out. It might look like a new drug is really promising (you’ve seen the headline: “male birth control, coming soon!”), but it might turn out with more research that it doesn’t work in a pill or a shot or a cream or an implant or any other way we deliver drugs. Maybe it turns out that it causes unwanted side effects. Maybe it works great, but it’s really inconvenient for men and couples to use…and the process slows down as researchers go back to the drawing board. These issues highlight the importance of conducting end-user research alongside drug development, a practice the IMPT has long advocated for with MPTs (like here and here).

Moreover, contraceptive drug development research is often funded by pharmaceutical companies that will ultimately sell the drug that comes from the research. But this isn’t happening with male contraception or MPT development; rather, individual scientists and smaller organizations are working to develop these new methods. This is part of the reason that development has been even slower than it is to develop some other drugs—money is admittedly tight, and researchers are essentially working individually or within small groups utilizing what financial and scientific support they are able to wrangle themselves.

MCI and the IMPT understand that new contraceptive methods are important, and together we are poised for innovation in the global sexual and reproductive health space. That’s why we are partnering to provide support for researchers working on the science behind these new methods, help advocate for increased funding, and catalyze conversations around the need for product innovation.

Male birth control and MPTs are on their way—it will just take a while. There are a lot of male contraceptive targets and drugs in the pipeline, and researchers are constantly coming up with more ideas. It remains to be seen which ones will make it to the market, but there are a lot of good potential options coming. The same can be said for MPTs as seen in this product pipeline database. In the meantime, MCI wants people to keep talking about male contraceptives, so that when they finally hit the market, men feel safe and comfortable taking them, couples are ready to incorporate them into their birth control plan, and providers know how to insert or prescribe them. The IMPT works to advocate for a similar approach with MPTs. So, talk to your partner, your friends, your kids, and your doctor to see what they think, and share information with them. Because together we can spark a product revolution! 

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A version of this post entitled “Male Birth Control: Where Is it?” was first published in September 2019 on the MCI blog.

If you would like to stay informed and join the male birth control conversation, follow MCI on Instagram, Twitter, and Facebook. There, we post information and updates about male contraceptives, and have lots of opportunities for you to share your perspective and ideas about male birth control.

About the Author

Male Contraceptive Initiative

The mission of Male Contraceptive Initiative (MCI) is to facilitate research and development of male contraceptives for people around the world and to build awareness of the status of novel male contraceptive methods.

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