AMAG Must Build Market For Approved Female Libido Drug To Avoid Addyi’s Fate
Executive Summary
AMAG Pharmaceutical’s HSDD drug Vyleesi, has been approved by the FDA. But analysts warn it must build the market in women who may not be aware they have a condition if it is to fare better than Sprout’s Addyi.
The US Food and Drug Administration has approved AMAG Pharmaceuticals Inc.’s Vyleesi (bremelanotide injection), a melanocortin receptor agonist, to treat hypoactive sexual desire disorder (HSDD) in premenopausal women.
The Vyleesi autoinjector is the first treatment for this patient population that can be self-administered as needed in anticipation of sexual activity.
The product will be commercially available in September through select specialty pharmacies, said the company, although analysts still retain some skeptism over market potential of the drug.
Analysts at Leerink said that “commercial potential of Vylessi remains an outstanding debate given its route of administration via injection and risks around market creation,” in a 23 June company update note.
Leerink analysts highlight the 6 million premenopausal women in the US (one in 10) with HSDD, of which the clear majority are not on therapy. AMAG’s strategy is to destigmatize the conversation, create an online community and focus on digital channels, much like it did for its vaginal atrophy drug Intrarosa (prasterone). But Leerink analysts believe AMAG “will have its work cut out to build this market”, as research suggests that 95% of women who have HSDD do not know they have a specific medical condition.
AMAG will work to improve on the fortunes of its only competitor in the market,Sprout Pharmaceuticals Inc.’s Addyi (flibanserin), which was approved in 2015 but has been unable to make in-roads in the market, so far peaking at around $13m sales in 2016.
Addyi has not been the commercial success its originators had hoped. Immediately following its approval, Valeant Pharmaceuticals International Inc., as was, acquired Sprout for $1bn. However, two years later, Valeant sold the subsidiary and Addyi back to its original owners in exchange for a 6% royalty on global sales of the drug. Payers had been questioning a price tag in the region of $800 for 30 tablets; the product needs to be taken every day. (Also see "Valeant Returns $1bn Female Libido Drug For Free" - Scrip, 7 Nov, 2017.)
Analysts at Jefferies has said in a 22 May note, based on AMAG’s analyst day, that “given the commercial failure of the same target market drug Addyi… commercial challenges remain although one could argue for difference in products' profiles.”
Addyi has a Black Box warning, is contraindicated with alcohol, and only available through a REMS program, while Vyleesi has none of these drawbacks. Its method of administration, however, has left some doubts in the minds of industry observers. (Also see "US FDA Squashes Sprout's Attempt To Remove Boxed Warning From Addyi Label" - Pink Sheet, 14 Apr, 2019.)
Leerink conceded that, while they had been concerned about the subcutaneous method of administration, they were surprised that physicians at AMAG's Analyst Day acknowledged how insignificant this issue was in the clinical trials. They also noted that nearly 80% of patients who completed the Phase III trials elected to remain in the open-label portion of the study.
Stephanie Yip, senior analyst at Datamonitor Healthcare, told Scrip, “The fact that Vyleesi is intended to be taken as needed is a key differentiating selling point for the brand over its once-daily competitor, Addyi. Although injections may not be the preferred route of administration for patients compared to oral pills, Vyleesi’s longer dosing schedule offers the benefit of convenience, which should drive its uptake.”
Leerink forecasts that Vyleesi can make around $90m per year by 2025, and sees the potential that Vyleesi can make inroads in this market where Addyi has not, and “be a much-needed growth driver for AMAG in the medium-to-longer term.”
RECONNECT Study
Bremelanotide is the first of a new class of drugs developed to treat sexual dysfunction, melanocortin agonists. It acts on the MC1 and MC4 receptors, the latter of which are associated with the regulation of metabolism, sexual behavior and male erectile function.
Vyleesi’s approval is based on two Phase III studies, named RECONNECT. The trials lasted for 24-weeks and enrolled 550 patients in each, in which they injected bremelanotide under the skin of the abdomen or thigh at least 45 minutes before sexual activity. Twenty five percent of patients had improved sexual desire scores compared with placebo patients (17%).
The FDA notes that patients shouldn't use more than one dose a day, or eight doses a month. Patients should stop treatment at eight weeks if they don't notice any improvement in sexual desire and distress.
The most common adverse events found in the trials were nausea, flushing, injection site reactions, and headache. In clinical trials, Vyleesi caused small, transient increases in blood pressure, and is contraindicated in women with uncontrolled high blood pressure or known cardiovascular risk.
AMAG in-licensed Vyleesi from Palatin Technologies Inc. in February 2017. Under the terms of the agreement, the approval of Vyleesi by the FDA triggers a $60m payment obligation to Palatin.
In addition, AMAG will pay Palatin tiered royalties on annual net sales of Vyleesi ranging from the high-single digits to the low double-digits. AMAG will also pay Palatin sales milestones based on escalating annual net sales thresholds, the first of which is $25m, triggered at annual net sales of $250m.