Berndt Modig, Pharvaris CEO

Phar­varis hits a snag with hered­i­tary an­gioede­ma pill as FDA places hold on tri­als

Swiss biotech Phar­varis an­nounced Mon­day that the FDA has placed a hold on the clin­i­cal tri­als for its oral drug PHA121 which aims at treat­ing hered­i­tary an­gioede­ma, or HAE, a rare ge­net­ic con­di­tion.

The reg­u­la­tors placed the hold af­ter re­view­ing the com­pa­ny’s non­clin­i­cal da­ta, Phar­varis said. The FDA’s de­ci­sion is a set­back for the com­pa­ny’s Phase II study, which aims to eval­u­ate the ef­fi­ca­cy and safe­ty of the drug.

Phar­varis is among the few com­pa­nies to de­vel­op an oral drug for HAE, a dis­ease char­ac­ter­ized by painful swelling in hands, feet, and oc­ca­sion­al­ly in the air­ways or in­testi­nal walls. While ef­fec­tive ther­a­pies al­ready ex­ist, such as CSL’s Hae­gar­da and Take­da’s Cin­ryze, Takhzy­ro and Fi­razyr, all of them are in­jecta­bles.

HAE is caused by a de­fi­cien­cy in the blood plas­ma pro­tein C1 es­terase in­hibitor, and both Hae­gar­da and Cin­ryze try to boost the lev­el of that pro­tein in the blood. Fi­razyr, on the oth­er hand, blocks bradykinin, a blood pro­tein that is over­pro­duced in HAE be­cause of in­creased lev­els of C1. El­e­vat­ed lev­els of bradykinin cause blood cells to leak and tis­sues to swell.

Phar­varis’ drug PHA121 is an oral pill that works as a bradykinin B2 re­cep­tor an­tag­o­nist. Phase I da­ta from 16 healthy vol­un­teers sug­gest their mol­e­cule is 24 times as po­tent as Fi­razyr, and the com­pa­ny has al­ready launched two Phase II tri­als: one for pro­phy­lax­is and one for treat­ing acute pain.

Oth­er com­pa­nies have tried to de­vel­op oral ther­a­pies for HAE, but so far on­ly one has crossed the FDA fin­ish line. BioCryst’s Or­ladeyo, ap­proved in De­cem­ber 2020, passed a Phase III tri­al, with the high­er dose re­duc­ing the an­gioede­ma at­tack rate by 44% ver­sus place­bo (p<0.001), while the low­er dose cut the at­tack rate by 30% (p=0.024).

Though an­a­lysts were left unim­pressed at the time af­ter sug­gest­ing that the drug need­ed least a 50% re­duc­tion of at­tack rate to en­sure com­pet­i­tive­ness, Or­ladeyo sales fig­ures have been on the rise. Af­ter pulling in $121.6 mil­lion last year, the drug net­ted BioCryst $114.9 mil­lion in the first half of this year alone, the biotech re­port­ed.

Mean­while, Phar­varis CEO Berndt Modig said the com­pa­ny was work­ing close­ly with the FDA to ad­dress the agency’s con­cerns. The com­pa­ny’s stock $PHVS fell near­ly 20% on Mon­day af­ter the com­pa­ny an­nounced the hold.

Phar­varis was found­ed by Modig, and oth­er vet­er­ans from Jeri­ni, the biotech that orig­i­nal­ly de­vel­oped Fi­razyr. In No­vem­ber 2020, the com­pa­ny raised an $80 mil­lion Se­ries C led by Viking Glob­al In­vestors and Gen­er­al At­lantic.

Ed­i­tor’s note: This ar­ti­cle has been up­dat­ed to clar­i­fy that BioCryst’s Or­ladeyo was ap­proved in De­cem­ber 2020. 

The Big Phar­ma dis­card pile; Lay­offs all around while some biotechs bid farewell; New Roche CEO as­sem­bles top team; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

With earnings seasons in full swing, we’ve listened in on all the calls so you don’t have to. But news is popping up from all corners, so make sure you check out our other updates, too.

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Trodelvy notch­es a win in most com­mon form of breast can­cer

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

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David Kirn, 4D Molecular Therapeutics CEO (via website)

FDA places hold on 4D Mol­e­c­u­lar’s Fab­ry gene ther­a­py

4D Molecular Therapeutics quietly tucked an FDA clinical hold on its Fabry gene therapy into an SEC filing.

Meanwhile, the biotech issued a press release the same day after the closing bell on Thursday touting an IND for another asset, in diabetic macular edema.

The California biotech had paused enrollment of patients in its two trials of the Fabry gene therapy (4D-310) last month after three patients experienced kidney issues, all of which were resolved within four weeks. At the time, 4DMT said it would wait until the second half of this year to look at 12-month clinical data on six patients in the Phase I/II trials, one in the US and one in Taiwan and Australia.

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Raymond Stevens, Structure Therapeutics CEO

Be­hind Fri­day's $161M IPO: A star sci­en­tist, GPCR drug dis­cov­ery and a plan to chal­lenge phar­ma in di­a­betes

What does it take to pull off a $161 million biotech IPO these days?

In Structure Therapeutics’ case, it means having a star scientist co-founder paired with the computational drug discovery company Schrödinger, $198 million in private funding from blue-chip investors, almost six years of research work on G protein-coupled receptors and a slate of oral, small-molecule drugs, with an eye on the huge and growing diabetes and weight-loss market.

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Af­ter 13 years, Ramy Mah­moud steps in­to CEO seat at Opti­nose; Ru­pert Vessey set to ex­it Bris­tol My­ers in Ju­ly

After 13 years as president and COO at Optinose, Ramy Mahmoud has stepped into a new role as its CEO. He is taking the place of Peter Miller, who stepped down earlier this week, though Miller is still staying with the company as a consultant.

In 2010, the two business partners joined Optinose to take it in a new direction, transforming it from a delivery platform to product company. They previously worked together at Johnson & Johnson, when Miller was president at Janssen and Mahmoud headed medical affairs. Miller said after he learned about Optinose, “I did what I always do, which is find people smarter than me to talk with about the idea. And the first person I called was Ramy … and I said, ‘Hey, Ramy, what do you think of this technology?’”

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Ma­gen­ta halts stem cell work and may sell it­self fol­low­ing pa­tient death, clin­i­cal hold

Magenta Therapeutics said it is halting work on its stem cell transplant drug pipeline and may sell itself, a week after the company reported the death of a patient in an early stage trial of its antibody-drug conjugate.

The Cambridge, MA-based company said it will conduct a “review of strategic alternatives,” and that could include an “acquisition, merger, business combination, or other transaction.”

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FDA ap­proves GSK's ane­mia drug with safe­ty warn­ing — af­ter bat­ting back sim­i­lar drugs

GSK has secured the first of four US approvals it’s hoping for this year, as the FDA greenlit daprodustat as a treatment for anemia due to chronic kidney disease.

But the FDA limited the use of the drug, to be marketed as Jesduvroq, to patients who have been receiving dialysis for at least four months and stopped short of approving it for patients not dependent on dialysis — in line with the recommendations of the advisory committee it consulted.

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Photo: Julia Weeks/AP Images

FDA ax­es re­quire­ment for pos­i­tive Covid test be­fore Paxlovid use

FDA announced today that doctors and pharmacists can now prescribe Paxlovid to patients without a positive test for Covid-19.

CDER Director Patrizia Cavazzoni reissued Paxlovid’s authorization letter Wednesday, saying it has revised the authorization to “no longer require positive results of direct SARS-CoV-2 viral testing.” The EUA now requires instead that adults and kids 12 years of age and older have a “current diagnosis of mild-to-moderate COVID-19.”