NDA Watch: TherapeuticsMD Inc (TXMD) and Yuvvexy

At the end of last week, female healthcare focused biotech company TherapeuticsMD Inc (NYSEMKT:TXMD) submitted a new drug application (NDA) to the FDA for its lead development candidate, Yuvvexy. The drug is targeting a condition called vulvar and vaginal atrophy (VVA), and specifically, a symptom of this condition called dyspareunia, which is moderate-to-severe vaginal pain during sexual intercourse.

There are a host of branded treatments currently available in this space, but TherapeuticsMD Inc (NYSEMKT:TXMD) is hoping certain features of Yuvvexy can set its candidate apart, and in doing so, give the company access to a double digit billion-dollar market.

Here’s a look at the science and the data behind the NDA.

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First, a quick look at the condition. It’s not too difficult to understand, and this makes explaining the MOA relatively simple as well. Vaginal tissue is composed of three primary different types of cell – superficial, intermediate and parabasal – with superficial (as the name suggests) the exterior layer cells, with intermediate and parabasal underneath. Healthy individuals have these three layers in something like the following proportion: superficial (>15%), intermediate (80%) and parabasal (<5%). In woman that have VAA, the ratio is more like this: <5%, 60% and >30%. The overly thin superficial layer causes dryness and friction related pain, while the excessive parabasal layer translates to a pH >5 (alkali), compared to a healthy pH of <5, exacerbating dryness and pain.

There are a few ways to tackle this problem. The first is to go after the symptoms, through things like lubricating gel and other topical formulations. Another is to go after the underlying cause – i.e. the lack of superficial cells – through hormonal treatment (estrogen). Yuvvexy is the latter. It’s a digitally inserted estrogen capsule that dissolves on vaginal insertion, and aims to increase the proportion of the vaginal wall that is composed of superficial cells.

The NDA is based on data from a phase III trial called Rejoice. The trial measured a host of endpoints against three doses (25 mcg, 10 mcg and 4 mcg) of Yuvvexy, and compared the results to a placebo arm, in post menopausal women with moderate-to-severe dyspareunia.

There were four co-primary endpoints – change in vaginal superficial cells, vaginal parabasal cells, vaginal pH, and the severity of dyspareunia. The trial hit on each of these endpoints, across all three doses, in as far as the active arms showed a stat-sig improvement over the placebo arms in each, as measured from baseline and again at 12 weeks.

So there’s the efficacy.

Safety also came in positive, with the only a few minor AEs reported, and patients generally reported as satisfied based on a post-study questionnaire. Indeed, by some quirk, two of the most common AEs (vaginal discharge and vulvovaginal pruritus) came in higher for the placebo arm than for the active arm.

Science done, data covered; what about the market? As mentioned, there are a few options available, and Yuvvexy aims to differentiate itself from each in a different way. For example, the biggest seller in terms of 2015 revenues is Pfizer Inc. (NYSE:PFE)’s Premarin. It’s a vaginal estrogen cream, and requires an applicator for self administration. This can be messy and inconvenient. Yuvvexy requires no applicator, and the capsule means no mess. The second biggest seller is Novo Nordisk A/S (ADR) (NYSE:NVO)’s Vagifem. These are oral administration tablets, take a while to have any effect, and require more constant administration that Yuvvexy is targeting.

Looking at the numbers, there are a reported 32 million women in the US that exhibit symptoms of VVA. Around 50% of these actively seek treatment. 50% of this treatment group use OTC products (creams, topicals, etc.). 36% have used HRT (i.e. the same MOA as Yuvvexy) but have stopped for one reason or another – generally unsuccessful or unsatisfied with the results. 14% use HRT treatments. TherapeuticsMD Inc (NYSEMKT:TXMD) is going after each of these three subsectors of the market – a reported $11 billion opportunity given current pricing and demand.

So what are we watching going forward? Well, the FDA is yet to accept the submission, but assuming everything is in order this should happen before the close of this quarter. Tack the standard review period of 10 months on to a conservative acceptance date (end September, 2016) and we could be looking at a PDUFA circa End-July next year.

Note: This article is written by Mark Collins and was originally published at Market Exclusive.