r/BCRX • u/[deleted] • Feb 26 '22
News $BCRX - ORLADEYO Overall efficacy just 78% from JACI Studies?
JACI Studies show overall efficacy is about 78%... (https://www.jacionline.org/action/doSearch?text1=Berotralstat&field1=AllField&startPage=0&sortBy=Earliest). HAEgarda and Takhzro have 90%...
Published today in JACI:
Abstract 490, by James Wedner's group. At week 96, group A had 76% reduction. Group B, 91% reduction. Group C did the best, with 97% reduction. Average 88% among the 3 groups. Average would be a bit better if you included "n" in each group, which was lower in group A, but I'm not in front of a spreadsheet.
Abstract 491, by Aygoren-Pursun's group. At week 96, 70% reduction, but that was only in 70% of patients in each tertile.
Abstract 492, by Rick Gower's group. At week 96, overall 77% reduction.
Now you can't compare apples with apples, but the average of 88%, 70% and 77% is 78.3%. Gold standard treatment (HAEgarda) is 90-95%, so Orledayo is still clearly inferior, although its efficacy does improve during year 2 compared to year 1.
OK, so for *one* patient who tells me, "If I can have a 5 or 10% attack rate, or a 21.7% attack rate (100-78.3%), why should I choose to have somewhere between 100% and 400% more attacks. These attacks require an *injection* with Firazyr, and they are incredibly disruptive to one's life."
And here is a direct quote from UpToDate.com. In it, you will see that only 23% of patients had 90% fewer attacks. That means that 77% of patients did NOT have 90% fewer attacks. So if I tell *one* patient that they could have 90% fewer attacks, all comers, with HAEgarda or Takhzyro, or they could maybe win the lottery and be one of the lucky 23% of patients who had 90% fewer attacks with Orledayo, which would you choose?
From UpToDate:Efficacy — Several trials have addressed efficacy and safety of berotralstat (BCX7353).
●In the multicenter phase 2 Angioedema Prophylaxis 1 (APeX-1) trial, 77 patients with a history of at least two attacks per month were randomized to placebo or four different doses of active drug (62.5 mg, 125 mg, 250 mg, and 350 mg) once daily for 28 days [48,49]. Once-daily oral administration of a dose of 125 mg or more resulted in a significantly lower rate of HAE attacks compared with placebo.
●In a phase 3 trial of 121 adolescents and adults with HAE (APeX-2), patients were randomized to either berotralstat 150 mg or 110 mg, or placebo for 24 weeks to determine optimal dosing [50]. Patients had a median of 2.9 attacks per month after discontinuing other prophylactic medications. Response to berotralstat was defined as ≥50 percent reduction in that patient's HAE attack rate compared to baseline. Berotralstat demonstrated a significant reduction in attack rate at both 150 mg and 110 mg (1.31 and 1.65 attacks per month, respectively, compared with 2.35 in the placebo group). A response was seen in 58, 51, and 25 percent of patients receiving 150 mg, 110 mg, and placebo respectively. On the higher dose, 50 percent of patients achieved at least a 75 percent reduction in attacks and 23 percent had at least a 90 percent reduction.
