FDA Approves New Treatment Combination of Gilead Sciences, Inc.’s (GILD) Letairis(r) with Tadalafil for Pulmonary Arterial Hypertension

gildGilead Sciences, Inc. (NASDAQ:GILD) announced that the U.S. Food and Drug Administration (FDA) has approved the use of Letairis® (ambrisentan) in combination with tadalafil for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to reduce the risks of disease progression and hospitalization for worsening PAH, and to improve exercise ability. Letairis is an endothelin receptor antagonist that was first approved in 2007 in the U.S. as monotherapy for PAH to improve exercise ability and delay clinical worsening. Tadalafil is a PDE5 inhibitor that was initially approved for PAH in the U.S. in 2009 to improve exercise ability.

“The evidence to support the use of ambrisentan and tadalafil in PAH is well-established, however an outstanding question has been whether combining these two medications up front may further delay the progression of this disease over the long term for patients who are newly starting PAH therapy,” said Ronald J. Oudiz, MD, Professor of Medicine, David Geffen School of Medicine at UCLA and Director, Liu Center for Pulmonary Hypertension, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center. “Based on the data supporting today’s approval, we now know that patients receiving ambrisentan and tadalafil up front are less likely to experience disease progression or be hospitalized, and have more improvement in exercise ability than patients receiving either effective therapy alone. As such, this combination represents a new treatment strategy for patients living with this debilitating and life-threatening disease.”

The new labeling is supported by data from the AMBITION study (a randomized, double-blind, multicenter study of first-line combination therapy with AMBrIsentan and Tadalafil in patients with pulmonary arterial hypertensION). In AMBITION, 605 patients with WHO Functional Class II or III PAH were randomized (2:1:1) to receive once-daily Letairis plus tadalafil (n=302) or to Letairis (n=152) or tadalafil (n=151) alone. Treatment was initiated with Letairis 5 mg and tadalafil at 20 mg. If tolerated, tadalafil was increased to 40 mg at four weeks and Letairis was increased to 10 mg at eight weeks. The primary endpoint was time to first occurrence of death, hospitalization for worsening PAH, greater than 15 percent decrease from baseline in six-minute walk distance (6MWD) combined with WHO Functional Class III or IV symptoms sustained over 14 days (short-term clinical worsening) or reduction in 6MWD sustained over 14 days combined with WHO Functional Class III or IV symptoms sustained over 6 months (inadequate long-term clinical response).

In the study, combination therapy with Letairis and tadalafil demonstrated superiority in reducing the risk of the composite primary endpoint by 49 percent and 45 percent, respectively, versus monotherapy with Letairis (hazard ratio = 0.51; 95 percent CI: 0.35, 0.73; p=0.0002) or tadalafil (hazard ratio = 0.55; 95 percent CI: 0.37, 0.81; p=0.002). Overall, 20 percent of patients receiving combination therapy experienced a primary endpoint event compared to 35 percent and 30 percent, respectively, in patients receiving Letairis or tadalafil.

Combination therapy also demonstrated a reduced risk of hospitalization for worsening PAH of 67 percent and 56 percent, respectively, compared to Letairis (hazard ratio = 0.33; 95 percent CI: 0.19, 0.55) or tadalafil (hazard ratio = 0.44; 95 percent CI: 0.25, 0.79). Overall, 8 percent of patients receiving combination therapy were hospitalized for worsening PAH compared to 22 percent and 15 percent, respectively, in patients receiving Letairis or tadalafil.

Patients receiving Letairis plus tadalafil also experienced statistically significant improvements from baseline in 6MWD versus individual monotherapy, with a median difference of 24 meters and 20 meters, respectively, from Letairis (95 percent CI: 11, 37; p=0.0004) or tadalafil (95 percent CI: 8, 32; p=0.0016) at Week 24.

When Letairis is used in combination with tadalafil, the common adverse reactions (>5 percent than on either monotherapy) were peripheral edema (Combination: 45 percent; Letairis: 38 percent; tadalafil: 28 percent), headache (Combination: 41 percent; Letairis: 34 percent; tadalafil: 35 percent), nasal congestion (Combination: 19 percent; Letairis: 16 percent; tadalafil: 11 percent), cough (Combination: 18 percent; Letairis: 13 percent; tadalafil: 16 percent), anemia (Combination: 15 percent; Letairis: 7 percent; tadalafil: 11 percent), dyspepsia (Combination: 11 percent; Letairis: 3 percent; tadalafil: 12 percent) and bronchitis (Combination: 10 percent; Letairis: 4 percent; tadalafil: 9 percent). Letairis has a labeled BOXED WARNING and an associated Risk Evaluation and Mitigation Strategy (REMS) program regarding the risk of embryo-fetal toxicity; see below for Important U.S. Safety Information for Letairis.

Data from AMBITION were published in The New England Journal of Medicine and Letairis plus tadalafil was the only recommended initial combination therapy option for PAH in the “2015 European Society of Cardiology / European Respiratory Society Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension” published in the European Heart Journal in August 2015.

AMBITION was cosponsored by Gilead and GlaxoSmithKline (GSK). Eli Lilly and Company also provided funding and tadalafil drug supply for the trial. Gilead commercializes ambrisentan under the tradename Letairis in the U.S. and GSK commercializes ambrisentan under the tradename Volibris® in territories outside of the U.S. (Original Source)

Shares of Gilead Sciences closed today at $98.28, up $0.01 or 0.01%. GILD has a 1-year high of $123.37 and a 1-year low of $85.95. The stock’s 50-day moving average is $105.92 and its 200-day moving average is $108.64.

On the ratings front, Gilead has been the subject of a number of recent research reports. In a report released today, Morgan Stanley analyst Matthew Harrison downgraded GILD to Hold, with a price target of $127, which represents a potential upside of 29.2% from where the stock is currently trading. Separately, on September 22, William Blair’s John Sonnier reiterated a Buy rating on the stock .

According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Matthew Harrison and John Sonnier have a total average return of 4.8% and 13.0% respectively. Harrison has a success rate of 48.1% and is ranked #1296 out of 3755 analysts, while Sonnier has a success rate of 50.0% and is ranked #490.

Overall, one research analyst has assigned a Hold rating and 11 research analysts have given a Buy rating to the stock. When considering if perhaps the stock is under or overvalued, the average price target is $128.00 which is 30.2% above where the stock opened today.


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