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Vertex CF Competitor Proteostasis Falters, Galapagos Up Next

Xconomy Boston — 

Data released Wednesday afternoon looks to have eased a potential threat to Vertex Pharmaceuticals’ burgeoning cystic fibrosis franchise, though news from another challenger looms later this month.

Proteostasis Therapeutics (NASDAQ: PTI) released data from a 49-patient Phase 1 study testing its experimental cystic fibrosis drug, PTI-801, in combination with Vertex’s (NASDAQ: VRTX) FDA-approved CF drug ivacaftor/lumacaftor (Orkambi).

In a press release, Proteostasis pointed to statistically significant changes the drug combo produced in patients’ “sweat chloride,” a surrogate marker for a therapy’s effect on CF patients. But the PTI-801/Orkambi combination didn’t lead to a statistically significant improvement in lung function—the gold standard for a CF drug’s effectiveness—over Orkambi and a placebo. Specifically, patients on a low dose of PTI-801 and Orkambi saw a 1.9 percent improvement in lung function after 14 days, compared to a 2.5 percent increase on a medium dose, a 0.6 percent increase on a high dose. By comparison, the lung function of patients on Orkambi and a placebo improved by 1.7 percent.

On a conference call Wednesday afternoon, Proteostasis executives pointed to a post hoc analysis showing that an acute drop in lung function occurred in many patients on Orkambi. Those that didn’t have the same reaction performed much better, meaning Orkambi may have masked the benefits of Proteostasis’ drug. “We regard this post hoc interpretation of the data as largely spurious, and still not quite competitive,” wrote Leerink Partners analyst Geoffrey Porges, in a research note.

Proteostasis shares fell 36 percent Thursday morning, to $3.15 apiece. The company went public in February 2016 at $8 per share.

Proteostasis is one of the companies trying to challenge Vertex, which has remade itself into the CF market leader over the past several years after its hepatitis C franchise was wiped out. Since 2012, the company has won FDA approval of three drugs: ivacaftor (Kalydeco), Orkambi, and ivacaftor/tezacaftor (Symdeko). Known as CFTR modulators, they are the first approved drugs to treat the molecular malfunction underlying the disease, which causes a steady buildup of thick mucus in the lungs and pancreas that leads to infections and other health problems.

These drugs aren’t cures, but they help improve lung function in segments of the CF population. Vertex has been developing a variety of multi-drug “cocktails” to treat a wider swath of patients—and dominate the CF landscape. It currently has two three-drug regimens in late stage testing, for instance, that, if effective, could help treat up to 90 percent of people with the disease.

Others are trying to break in with similar plans, among them Proteostasis. PTI-801 is part of two multi-drug regimens—a two and three-drug cocktail—set to begin Phase 2 testing shortly and produce results later this year. AbbVie (NYSE: ABBV), through a partnership with Galapagos (NASDAQ: GLPG), is also in the mix. This month, Galapagos will report data from a Phase 2 study, PELICAN, that combines its experimental CF drug GPLG-2737 with Orkambi.

Today’s data lessens the likelihood that Proteostasis will threaten Vertex, Porges wrote. Sweat chloride reduction “has never been accepted as a surrogate endpoint for approval,” as opposed to lung function changes, he wrote. Porges deemed PTI-801 “a marginally effective CFTR modulator” that “will not be competitive” with Vertex. “We also believe this result challenges Proteostasis development plans for a proprietary triple [combination]…which would be the company’s only avenue to compete head-to-head, rather than be a complement to Vertex,” Porges wrote.

Here’s more on Vertex, Proteostasis, and the landscape of cystic fibrosis drugs.