Apel­lis bags FDA nod for Soliris chal­lenger with a dif­fer­ent path­way to PNH — but can it slay the gi­ant?

With a block­buster rare dis­ease gi­ant in its sights in Alex­ion’s Soliris, small biotech Apel­lis has rea­son to think its com­peti­tor is wor­thy of the spot­light. Now, with the FDA on its side, Apel­lis will get its chance to be the David to Alex­ion’s Go­liath.

The FDA on Fri­day ap­proved Em­paveli (pegc­eta­coplan), a C3 com­ple­ment in­hibitor the biotech thinks can prove a wor­thy chal­lenger to Alex­ion’s C5 in­hibitors Soliris and fol­low-up drug Ul­tomiris in rare dis­ease parox­ys­mal noc­tur­nal he­mo­glo­bin­uria (PNH).

In piv­otal Phase III da­ta on which the agency based its re­view, Em­paveli best­ed Soliris in a head-to-head test in terms of he­mo­glo­bin pro­duc­tion with a rel­a­tive in­crease of 3.9 g/dL (p<0.0001), and some fa­vor­able trend lines in sec­ondary end­points such as trans­fu­sions and fa­tigue.

Em­paveli will come with the same black box warn­ing la­bel as Soliris, re­strict­ing use un­der a risk eval­u­a­tion and mit­i­ga­tion strat­e­gy for meningo­coc­cal in­fec­tions. The ther­a­py was ap­proved for pa­tients re­gard­less of pri­or ther­a­pies, mean­ing its use won’t be re­strict­ed to for­mer C5 pa­tients alone.

On a call with an­a­lysts Mon­day, Apel­lis said Em­paveli would come with an av­er­age an­nu­al whole­sale ac­qui­si­tion cost of $458,000. That’s “at par­i­ty” with Ul­tomiris and a dis­count on Soliris, the com­pa­ny said.

Apel­lis thinks that a big bump in he­mo­glo­bin lev­els could help it im­me­di­ate­ly cap­ture about a third of the ex­ist­ing PNH pa­tients who have a low and falling he­mo­glo­bin count that is cur­rent­ly un­der­served by the C5 drugs, CEO Cedric Fran­cois told End­points News pri­or to the ap­proval.

“If the Phase III study did one thing it is mak­ing it very clear that by con­trol­ling ex­travas­cu­lar he­mol­y­sis, you can el­e­vate the stan­dard of care in these pa­tients,” Fran­cois said.

The key to Apel­lis’ pitch is C3, which it be­lieves can of­fer a longer-last­ing so­lu­tion for he­mo­glo­bin pro­duc­tion as C5 of­ten doesn’t boost lev­els for more than a few days, the team said. With an ap­proval in hand, Apel­lis said it plans to tar­get those 500 or so US pa­tients with the low­est he­mo­glo­bin counts but thinks Em­paveli could have a mean­ing­ful up­take across the en­tire PNH spec­trum.

The com­pa­ny has al­ready built up a sales team that has been do­ing some of the ground­work on physi­cian out­reach in the lead-up to ap­proval. It’s a small group of PNH spe­cial­ists, and Apel­lis thinks it’s found a work­able, hy­brid dig­i­tal/in-per­son ed­u­ca­tion cam­paign to tell doc­tors about the drug’s ben­e­fits.

But beat­ing Alex­ion — and soon to be As­traZeneca — won’t be an easy task by any means. Alex­ion’s en­tire fran­chise was built around build­ing Soliris in­to a block­buster, and the com­pa­ny has been busy amid a gung-ho switch­ing cam­paign to fol­low-up drug Ul­tomiris.

As­traZeneca an­nounced its in­tent to buy Alex­ion late last year for a cool $39 bil­lion. The rare dis­ease spe­cial­ist will im­port its ex­pan­sive port­fo­lio of C5 drugs, which sport in­di­ca­tions be­yond PNH.

This sto­ry will be up­dat­ed.

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.”