Thank you for standing by, and welcome to the Evofem Biosciences fourth quarter and year-end 2021 results conference call. At this time, all participants are on a listen-only mode. After the speakers' presentations, there'll be a question-and-answer session. To ask a question at that time, please press star then one on your touchtone telephone. As a reminder, today's conference call is being recorded. I will now turn the conference over to your host, Ms. Amy Raskopf, Vice President of Investor Relations. Ma'am, you may begin.
Thank you, Valerie. Good afternoon, everyone, and welcome to the Evofem Biosciences Q4 and year-end 2021 results call. If you haven't done so already, I encourage you to access the press release we re-issued this afternoon and slides that accompany this call, both of which are at evofem.com under the Investors tab. Before we begin, I would like to remind you that remarks made on this call will contain forward-looking statements, which are made only as of today, March 3, 2022. For a more detailed description of important risk factors that could cause our actual results to differ materially, please refer to our annual report on Form 10-K and our most recently filed 10-Q. With that, I'll turn the call over to Evofem's CEO, Saundra Pelletier.
Thank you, Amy, and I wanna thank everyone for joining us today on the call. Evofem delivered strong growth in the fourth quarter of 2021. Net product sales of Phexxi for hormone-free birth control more than doubled in Q4. It increased 109% to $3.6 million. This reflects the hard work of our sales organization, the impact of our innovative marketing campaigns, and ongoing growth to net improvements. We are excited to build on this foundation in 2022 and beyond. Additionally, we made significant progress in our program developing Phexxi for the prevention of chlamydia and gonorrhea. Today, literally today, we completed enrollment in our registrational phase III EVOGUARD trial ahead of the schedule we discussed on our Q3 earnings call with more participants than called for in the study protocol.
This was due to very strong interest in the trial and high screening levels. We also received Qualified Infectious Disease Product designation from the FDA for prevention of chlamydia. This affords us five years additional market exclusivity on approval. I'll discuss next steps for this program in greater detail amongst other initiatives to build shareholder value after our CFO, Jay File, reviews the financial results. Jay?
Thank you, Saundra. Today I'm going to focus on the fourth quarter of 2021 relative to Q3. For our year-end results, please reference our Form 10-K to be filed in the next few days. Net product sales increased 109% to $3.6 million, driven by a 73% increase in Phexxi units shipped. Research and development costs were unchanged at $8.7 million, reflecting clinical trial expenses for the phase III EVOGUARD trial of Phexxi for the prevention of chlamydia and gonorrhea in women. Selling and marketing costs were $24.9 million, down 18% as expected. This was due primarily to lower media expenses related to the Annie Murphy DTC marketing campaign. General and administrative costs were $5.7 million, up 14% primarily due to increases in outside services and payroll-related expenses, including stock-based compensation.
As a result, total operating expenses decreased to $41 million, and our loss from operations was $37.4 million. We reduced our net cash burn to $16.8 million in Q4 versus $32 million in Q3. For 2022, we expect net product sales will be in the range of $30 million-$35 million. Momentum should build as planned, and pharmacy benefit managers or PBMs adhere to the updated federal guidelines that are expected to expand access to Phexxi at zero out-of-pocket costs for commercially insured women. With this expanded coverage for Phexxi, gross net should improve to the 35%-40% range. We believe this, coupled with significantly lower R&D costs once we complete the treatment phase of the EVOGUARD trial, will get us to cash flow breakeven on a quarterly basis by the end of 2023.
At the close of Q4, we had $7.7 million in cash and cash equivalents, as well as $5.1 million in unrestricted cash from the Adjuvant Notes available for use. In Q1 2022, we raised $10 million in gross proceeds to the company through two unsecured debt transactions. We also secured a $50 million equity line of credit that gives us flexibility should we need it. Finally, we received a notice from Nasdaq last week that Evofem remains not compliant with Nasdaq listing standards because we do not currently meet the $1 minimum bid price requirement. We have requested a hearing with Nasdaq Listing Qualifications Panel to present our case for additional 180 days to meet their requirements, which we expect to take place by mid-April. This request postpones the delisting process until the hearing.
We fully expect that our presentation at that hearing will be received favorably and that we will be granted an additional 180 days to comply with their share price requirements. With that, I'll turn it back to Saundra.
Thanks, Jay. Our substantial growth in Q4 was driven by the House Rules DTC campaign starring Emmy Award-winning actress Annie Murphy, in addition to the targeted efforts of our sales force with OBGYNs, nurse practitioners, and midwives. Nearly 40,000 boxes of Phexxi were dispensed in Q4, up 81% from Q3, and total prescriptions grew nearly 70%. Almost 23,000 new patients started Phexxi in Q4, up 56% from Q3, which is a strong reflection of our success in driving demand. Nearly 69,000 women have come through our telehealth platform to date, and the vast majority of them are under the age of 35. While the largest segment is 25 to 34 year-old women, more than 30% of these women are between ages 18 to 24 years old. We are implementing programs this year to further expand Phexxi use in these segments, and particularly among college-aged women.
With our strong established prescriber base, our sales team is now focusing on increasing the volume of prescriptions from each provider. We will launch a national HCP campaign at the annual meeting of the American College of Obstetrics and Gynecologists in early May, aimed at increasing awareness of Phexxi among prescribers and broadening patient segments. The end goal is to increase the percentage of women who will be offered Phexxi and boost prescriptions from each practice and from each prescriber. We are very pleased with the direction that things are moving relating to access for Phexxi. One of our key objectives that we laid out on the Q3 call was to spur federal action to mandate coverage of all FDA-approved contraceptives, including Phexxi, at zero out-of-pocket cost to the patients under the ACA. I am proud to say that we met that goal.
In January, the Health Resources and Services Administration, or HRSA, and the U.S. Department of Labor updated guidelines preventing the FDA birth control guide from limiting contraceptive access. They require that most commercial insurers and PBMs cover new and unique contraceptive options such as Phexxi. They specifically state that the plans may not require patients to try and fail multiple options before covering a different product if a provider deems that product medically necessary. These updated guidelines are significant. As plans begin to evaluate their practices to comply with them, access to Phexxi is expected to increase. With the removal of payer restrictions, like step edits and denials of coverage, followed by coverage for Phexxi at zero out-of-pocket cost to women, we expect our business will dramatically improve. The guidelines from the Departments of Health and Human Services, Labor, and the Treasury took effect immediately in January.
However, we understand that there are certain insurers that find legal and semantic loopholes to avoid compliance. To combat this, in February, a letter signed by 34 U.S. senators was sent to these departments calling for heightened enforcement of the ACA requirement that insurance companies cover all FDA-approved forms of birth control at no cost to patients. The letter targets these non-compliant insurers that are not following the guidelines as intended. Now, turning to R&D. We have made tremendous progress with our program to develop Phexxi for the prevention of chlamydia and gonorrhea in women. The unmet need here is significant due to the increasing incidence as well as the rise of antibiotic-resistant strains. Every sexually active woman, no matter what form of contraception she's using, is at risk to contract one of these STIs.
Chlamydia is the most frequently reported bacterial infection in the United States, and gonorrhea is number two. The CDC estimates that 4 million new cases of chlamydia occurred in 2018, resulting in a direct medical cost of almost $700 million. There are 1.6 million new cases of gonorrhea. Cases are underreported because infected people are often unaware that they have these sexually transmitted infections. Up to 70% of women infected with chlamydia have no symptoms. Untreated, this can lead to major health problems. Chlamydia is a primary cause of pelvic inflammatory disease and infertility in women. Based on FDA action in February, Phexxi is now qualified for an additional five years of marketing exclusivity following FDA approval for either chlamydia or gonorrhea or both. This stems from our Qualified Infectious Disease Product designation for both potential indications.
We also have fast-track designation for both indications, which means the FDA will review our regulatory submission in six months versus the usual 10-month period. Earlier today, we achieved full enrollment in our registrational phase III trial of Phexxi to prevent chlamydia and gonorrhea. We met this milestone a month ahead of the schedule discussed on our Q3 conference call. This reflects the discipline and the rigor of our clinical team, along with the high level of demand to participate and the desire for a new FDA-approved preventative measure. I want to thank our study centers as well as the many women who are participating in this landmark study. As a reminder, this is a double-blind, placebo-controlled clinical trial.
Achieving the primary endpoint would allow us to file for regulatory approval with the FDA with the end goal of expanding the Phexxi label to include prevention of chlamydia and gonorrhea in women, as well as hormone-free birth control. With enrollment now complete, we are on track to report top-line data in the second half of the year, followed by regulatory filings in the first half of 2023, with potential FDA approval expected by the end of 2023. Phexxi would be the first and the only FDA-approved product to prevent these STIs. Again, every sexually active woman is at risk. We believe this represents a large market opportunity for Evofem in the United States and around the world.
Meanwhile, with an eye toward pipeline expansion, we entered into a collaboration with Orion Biotechnology to evaluate the compatibility and stability of Orion's novel CCR5 antagonist in Phexxi, targeting HIV prevention, among other indications. Our collective goal is to develop a new product candidate with potential to be the first and the only product to protect against unintended pregnancy, STIs, and HIV. We expect results of this initial preclinical work in the third quarter. Assuming positive results, we will seek government grants and philanthropic funding for subsequent clinical trials of the MPT product candidate. This goes hand in hand with the work we are doing under our 2020 Global Health Agreement with Adjuvant Capital. In the fourth quarter, we submitted our regulatory registration in Mexico, followed by Nigeria and Ethiopia in January 2022.
The goal of this work is to ensure that safe, effective, high-quality contraceptive and STI prevention products are made available to women and healthcare providers in low and middle-income countries on terms that are commercially viable for Evofem. We look forward to the day when all women, regardless of their income, regardless of their geography, will have access to hormone-free birth control that they can use on their terms, only when they need it. With that, operator, I would like to open the call for questions.
Thank you. Again, ladies and gentlemen, if you'd like to ask a question, please press star then one on your touchtone telephone. Again, to ask a question, please press star then one. Our first question comes from David Amsellem with Piper Sandler. Your line is open.
Thanks. Just a couple. First, you mentioned, Saundra, how certain insurers are potentially looking for loopholes here. I guess what I'm trying to, you know, gauge is what do you think is the risk that you still see some plans, potentially large plans, you know, not covering the product the way it's supposed to be covered? You know, what do you think that could mean for 2023, sorry, this year and beyond. Just help us understand just the overall risk level. Secondly, as far as the mechanics of all this happening, I think you had stated that this is, you know, mainly gonna be a 2023 impact.
Do you think there's a chance that this could be pulled through sooner? I guess where I'm going with this is that $30 million-$35 million sales guidance, does that contemplate meaningful impact of coverage at zero copay? We're just trying to get a sense of what your underlying assumptions are there. I'll start with those.
Yeah.
Yeah.
Okay, great. Thanks, David, very much. Okay.
Mm-hmm.
All right. Let me try to unpack that, you know, logically. One, the projections that we gave, the $30 million-$35 million, does not contemplate a positive floodgate this year of ACA. It does not. We wanna be very realistic with the guidance that we're giving. I'm sort of starting at the end and going backwards. To your point, January 2023 is really kind of the silver bullet, meaning that's when the mandate is going to. All the plans that are still blocking have said that they basically have this year to decide, are they gonna enact early? Are they going to, and to do the right thing and give women coverage? Here's what I would tell you, is that right now we have about 70% coverage.
The plans that are the culprits are two plans, UnitedHealthcare and Express Scripts. If you could call them, David, and tell them to stop it, I would be incredibly grateful. Here's the deal. Here's what we've done, is that because of this mandate, they would say things to us like, "You're gonna have to give us a 60% discount and a three-year contract, or we won't cover Phexxi." We've said, "You know what? That's lunacy. Like, we're never doing that. That's craziness." Our reps are doing prior auths. We have trained our sales force. Now, look, I know some people might say, "Oh, yeah." Prior auths are a pain for offices.
They're not just an easy layup, even though our prior auth, I mean, this is one of the most simple prior auths I've ever seen, and I've been in this industry forever. Our reps literally, when we know that it's geographies that are heavily UnitedHealthcare or Express Scripts, our reps insist that all of these prior auths go through. They actually go into the offices. They are willing to help the staff do it so that the scripts are getting covered, is what I would tell you. We've actually heard from UnitedHealthcare that we are torturing them with prior auths, which we love.
We say, "Well, we'll stop it if you just do the right thing for women." The good thing that has happened though, David, is that they are not telling women they have to fail on seven or eight products, and that was literally what they were telling women. Women with cancer who can't use hormones anyway ever again were being told they had to fail on seven or eight products, and obviously, they can't, there are not even seven or eight products for them to take. One, that's been a huge improvement. Two, I would also tell you that those two plans have said to us that they're very interested in playing ball, and that between now and January, that they will consider some kind of a contract or agreement that is a discount less than 60%, in the 30% range.
I would tell you that the mandate has helped. It's given much more reasonable percentage terms. For anybody listening that wonders is that high or low, that's kinda standard, frankly, what happens in the industry, not the 60%, the 30%. I would tell you the numbers that we have now don't reflect it. I would tell you that many of the smaller plans adopted it already. They knew the writing was on the wall, and they'd have to. That's why our coverage has increased. We've actually already seen very, very positive coverage increases already. You know, at one point, we were 50%, 60%. We're 70% now. But I would tell you that, you know, we still have some struggles with some of the two big players, but the prior auths are still getting coverage for women.
Okay, that's helpful. Let me sneak in a follow-up. You talked about the gross to net of 35%-40% this year. What do you think the gross to net's gonna be after this year once we're, as you noted, finally sort of seeing the real impact of the mandate at zero copay?
Yeah. Jay, you wanna answer?
Yeah. Hi, David. It's Jay. That estimate with gross to net is with the full impact of 2023, so really rolling into 2023, not 2022. I can say that early looks into 2022, we are seeing some favorable impacts in gross to net as we kind of outlined a little bit on our prior call for Q3 results with turning off denial conversion. As you can imagine, that did have a positive lift, and we're already seeing it decrease from the low 70s% down into the low 60s%, and we do anticipate that will be a trend that will continue.
Just to be clear, Jay, that 35%-40% is how we should think about steady-state gross to net going forward?
Yeah. That should be kind of where we would like to get to by the end of 2023, and I think that even could be better from after that as well. We think that's a reasonable approach to kind of if you're looking to go forward in 2023.
Okay, great. Thank you.
Great. Thanks, David.
Thank you. Our next question comes from Annabel Samimy of Stifel. Your line is open.
Hi, this is Stacy calling in for Annabel. Thanks for taking our questions, and congrats on the fourth quarter numbers. Two questions. First one is, how much copay assistance was baked into the fourth quarter relative to the third quarter? Secondly, guidance has already taken effect this year. Have you seen any evidence of benefits from an access perspective? Prescription trends are, you know, showing their typical first quarter patterns, which presumably shouldn't be pronounced with a $0 copay, or would you say it's still too early to tell? Thank you.
Jay, do you wanna take the first one?
Yeah, I'll take the first one. Yeah, no, that's a great question actually because Q4 is an interesting kind of anomaly with how gross to net works. Copay assistance itself in theory was on as kind of a full bore approach with denial conversion on technically through the entire fourth quarter of last year. However, how we forecast gross to net knowing that it was turning off in January does have a positive impact on how we calculate gross to net in December. Long story short, we did see some lift in gross to net in Q4, not the majority 'cause October and November were full blast.
Q1 of this year will be the very first quarter where we have the full implementation of our adjustments to the copay program, and you'll see that reflected in our net revenue number for the quarter.
To the next question. We have already seen a lift. We have. There are some small and middle plans that frankly, they saw the writing on the wall, right? When this new mandate came out, they knew that it was inevitable. Now, for example, some of them said, "Well, you know, we update our system administratively at the beginning of the year or the middle of the year. So we will update it in July." But the majority said, "Look, this is inevitable, and we understand that the legislative mandate is intended to give a woman zero out-of-pocket pay for one product in every category." That's what the intention is under ACA. A lot of the plans have done it already, and so we've already seen that positive uplift.
You know, as I said, you know, to the answer to David's previous question, you know, there's still two big players that are culprits that we are whittling away at. To be honest, even the conversations with them are much more positive. We feel good that we're already seeing increased access without question already out of the gate. I also appreciate your point too. You know, January is always hard for any company for script growth. We actually are very, very positive and optimistic that the coverage is continuing to grow and, you know, it's just a matter of time.
Amazing. Thank you so much.
Yeah, thank you.
Thank you. Our next question comes from Raghuram Selvaraju of H.C. Wainwright. Your line is open.
Thanks so much for taking my questions, and congrats on all the progress. I just wanted to know when you anticipate you might be in a position to provide some frame of reference with respect to revenue guidance for 2022. Also wanted to see if there are specific metrics that you expect to be in a position to provide as we go further into the year pertaining to effectively, you know, the commercial performance of Phexxi. And also, if you could maybe comment on, you know, with respect to those insurers who are likely to be more reluctant who are actively looking for ways to get around the guidance, you know, if you can quantify to what extent those insurers represent, you know, X percent of covered lives that you're seeking to reach with Phexxi? Thank you.
Yeah. Jay, do you want to talk about first the guidance?
Yeah, sure. Ram, you might have joined the call late. We did give an idea that we are expecting 2022 net revenue to be somewhere between $30 million-$35 million for 2022.
Okay, great. Thank you.
Yeah. Like, is there any specific metrics that we're gonna be giving?
Yeah, I think, you know, it's fair to say that we're gonna continue to assess what makes sense to give guidance-wise and metrics as the quarters go on. I wouldn't necessarily say we're not willing to give more guidance. We're continuing definitely to get a better understanding of what the commercialization is and some of the underlying metrics that are used on that. You know, last year was our first twelve months of the year, and now we've made some adjustments to the co-pay program. Not to mention the reset with insurance at the beginning of the year. We do wanna get some bit of a level playing field under this new kind of environment.
I think as the year goes on, we'll be much more comfortable to probably expand on some of the guidance we've been given, and try and be a little bit more insightful on some of those.
Yeah. Ram, to the point about, you know, these plans that are really trying to find these loopholes, I would say. Look, we still have about a 30% gap to get to our goal of 100% coverage, and our goal of 100% coverage is not unrealistic. I mean, it's realistic particularly because of the category, right? The tough part for us is that, you know, UnitedHealthcare and Express Scripts do represent a lot of lives. The interesting part is that the prior authorizations have become a daily part of the rep sales call, right? In the areas in which UnitedHealthcare and Express Scripts are, you know, the big players, so to speak.
Although we don't like it, you know, we wanna be very transparent with the shareholders, you know, in hopes, frankly, that maybe one of them are on the board of UnitedHealthcare and Express Scripts, frankly. You know, I don't wanna seem delusional and say, "Oh, you know, we don't think it's a huge issue." Our leadership of our sales team was at our corporate office this week, and we had a very serious come to Jesus about, you know, how difficult is this? We know 2023, it's gonna be great. Frankly, they said, "Look, these reps are so keenly focused on prior auth because they know that's how they're gonna get their money, how they're gonna get paid." I would tell you that we're still getting those scripts through. I don't wanna misrepresent that.
Yes, it's not great. We wish the plans would comply to the law, and we know the way the law is intended, but we still are getting those scripts covered almost 85% of the time. There's still a percentage of the time that they're not going through, but we actually see our business growing this year. You know, I feel good about that.
Okay. Just two other very quick ones. Firstly, with respect to the Orion collaboration, you know, you had talked about, you know, HIV infection and some other indications. Can you elaborate on what the other indications might be?
Well, here's what I would tell you. Yes. The first and foremost, they're looking at HIV. What I said or what I meant was that, you know, this product could prevent pregnancy, prevent STIs and HIV. They're also looking at HSV. The bigger thing with this partnership that I think is gonna be most interesting is we are looking at two different delivery systems. We're obviously looking at the gel in an applicator as it is now, but we're also looking at a thin film. Almost like when you look at those breath mints, those Listerine that you know can put on. They dissolve on your tongue.
We're looking at a thin film vaginally applied to dissolve as the method that this new, you know, this new drug would be in so that we can take it all over the world, obviously. You know, cost of goods, our biggest cost of goods right now is our applicator. We've actually done a great job looking at all of our costs. But if we can use this new formulation of this thin film, and we're working in combination with the inventor of Phexxi, a gentleman named Dr. Sanjay Garg, then that's what I think is gonna be an incredible innovation. That's what's gonna be game changing. Really the focus is mostly HIV, not much other indications. It's just a way to, you know, figure out to be the first and the only product that will be able to deliver results for that.
Okay. Just wanted to make sure I fully understood, with respect to the business development initiatives on Phexxi outside of the United States, can you give us kind of a sense of what direction those are heading and when you might anticipate being in a position to announce something on that front?
Yes. One of the reasons that the process has been slowed slightly by us is because some of the countries, the contraceptive market is not as fruitful. The U.S. is the largest market opportunity for contraception. There is just no question the profit that can be made in the U.S. Some of the markets where we've talked to partners, it's over the counter. We really want this asset to be valued appropriately, not just with an upfront payment, with the milestones and the royalties. Some of the companies who are very interested in Phexxi, they came back to the table really doing a full market assessment to say, yes, there's a big opportunity, but once you get chlamydia and gonorrhea indications, it's game-changing because then it's a drug, then it gets registered differently. There's a whole different valuation system that applies to it.
What we really found is that some of the players that can give us the most non-dilutive upfront capital and the best and most significant milestones and royalties are the ones that really want the STI indications. We didn't want to give away market and just take in any money we could get for contraception and know that we would lock up those markets when we know a much bigger player with a lot more money wants to come to the table once we have our top-line readout. That's what we've really done. We've slowed the process down a little bit.
We still intend to make an announcement this year, but as you heard on the call, we are not gonna release our top-line data until the second half of this year, you know, end of third, fourth quarter timeline, because obviously, right, we need to collect the data, clean the data, all of that. That's really the reason that we haven't made an announcement. Now, we have had ongoing parties interested in Asia-Pacific and Latin America. The EU market, we've had interest, but that is one of the exact culprits I'm talking about, meaning that the contraceptive market is just not that fruitful. There's just not a lot of money to be made.
The bottom line is, there are a lot of parties interested, which we appreciate, but we think it's gonna be better for the company and the shareholders and frankly, access for women, if we hold off a little bit longer until we get closer to our readout for chlamydia, gonorrhea.
Thank you.
Thanks, Ram.
Thank you. Our next question comes from Jeff Hung of Morgan Stanley. Your line is open.
Thanks for taking the questions. What has the refill rate been like for Phexxi, and how are you thinking about the refill rate in 2022 for your net product sales guidance? Can you talk about the profile of women who are refilling scripts and how that compares to what you had been expecting earlier in the launch? Thanks.
Yeah. No, thanks for the question, Jeff. In December, they were 37%, which is actually a little ahead of what we expected. The one thing that we continue to say, and I know I'm a bit like a broken record here, but that Phexxi is on demand. I know that some people wanna look at refills for other contraceptive products that are much like rinse and repeat, right? You get your pill every month 'cause you take your pill every day, and Phexxi is on demand, so entirely different. 37% was December. We actually feel that that's gonna grow. I mean, I know this is a captain obvious statement, but one of the reasons we're so interested in this young constituency that we've attracted is they're gonna be on contraception a lot longer, you know.
We're gonna be able to capture these women now and hopefully have Phexxi users for the rest of their fertility years. The one thing that I am most excited about, frankly, is the young demographic, right? The majority of our users are under 35. When we first launched, I did get a lot of questions, is this product just for women who live in, who are in monogamous relationships and live in suburbia and have sex one day a month? No, that's definitely not the case. We actually have found this huge groundswell of young women who say I would tell you this, there's a self-care movement that is happening. Yes, it's been happening for a while, but COVID has made it happen faster.
These young women, now that they're back on college campuses, we get inundated with feedback from them, asking if they can do studies, if they can, you know, they wanna do a whole health day. Our new head of commercial has some very creative ideas on how we're going to target these campuses, talking about maybe having something called a SHAG week, which is sexual health and awareness. The young constituency is growing, and it's growing, you know, 18-25, as I said, is about 30%. We really feel like those are the women that are using the product properly. They love the product. They're talking about it on social media. They're telling all their friends about it so much more, you know, than a little bit older patient profile.
I don't know if that answers your question, but what we're seeing right now in the refills, and I know this is broad, it is the 18-35. That's a big range. We're trying to capture the younger woman constantly, and this is the year that we intend to do it.
Thanks. Just to clarify, so then for your net product sales guidance, are you assuming a rate higher than 37%, and is it meaningfully higher, or is it more driven by growth in younger patients?
Go ahead, Jeff
Yeah, no, I wouldn't necessarily attribute it exactly to a higher refill rate, but we do anticipate that it's going up. Keep in mind, obviously, 2021, we're emerging out of COVID. You know, I know everyone says it, but obviously, considering what our product is, that does get affected, and we're starting to come out of that. We think that's going to be a positive lift. Then also too, with the new guidelines as well, with those going away and impacting co-pays, we think that's going to be a positive lift as well. I think by natural default, yes, we do anticipate that will continue to grow, and that's ultimately what we're expecting to see over the next course of the year.
All right. Thank you.
Thank you. This concludes the question and answer period. I'd like to turn the call back over to Saundra Pelletier for any closing remarks.
In 2021, we asked investors to be patient so that we could build our foundation of women who love Phexxi, so we could build our foundation of prescribers who will write Phexxi for them, so that we could have our DTC outreach to build a brand for Phexxi and build a brand for Evofem as the company that will continue to deliver on innovation. We understand that patience is not always a virtue. However, you have heard on this call that the wait is over. We are committed to delivering on revenue growth, improvements to gross-to-net, and building our Phexxi franchise. Much has happened since our last earnings call, and all of it is positive. All of it. Demand for Phexxi increased significantly in Q4 with 109% growth in net product sales.
Our total prescriptions grew by 70%, and our units shipped increased by 73%. Our total operating expenses decreased, and we significantly reduced our net cash burn. We expect this will continue to trend down in 2022. We raised $10 million in unsecured debt and obtained a $50 million equity line of credit. The federal government took a crucial step in increasing women's access to contraception without copays. We completed enrollment in the EVOGUARD trial one month ahead of schedule. We received Qualified Infectious Disease Product designation for the prevention of chlamydia. We submitted regulatory registrations in Mexico, Nigeria, and Ethiopia. We entered into a collaboration with Orion Biotechnology to explore the development of a new product candidate that could protect against unintended pregnancies, STIs, and HIV.
Abraham Lincoln said, "Things may come to those who wait, but only the things left by those who hustle." Our performance in Q4 clearly demonstrated our drive and our ability to hustle. We are confident that 2022 is going to be the year of Evofem. Thank you so much for your time and attention.
Thank you. Ladies and gentlemen, this does conclude today's conference. Thank you all for participating. You may now disconnect. Have a great day.