Days af­ter FDA clears C3 drug, Apel­lis spot­lights ex-US PhI­II win among pa­tients who haven't tak­en Soliris

Through­out Apel­lis’ de­vel­op­ment pro­gram for pegc­eta­coplan — es­pe­cial­ly lead­ing up to its ap­proval days ago — CEO Cedric Fran­cois has of­ten billed its C3 in­hibitor as a chal­lenger to Alex­ion’s block­buster C5 drug Soliris, and it sug­gest­ed as much in the piv­otal study lead­ing to the FDA’s green light.

Cedric Fran­cois

But out­side the US, there are mar­kets where pa­tients may not have ready ac­cess to Soliris. And Apel­lis says it now has the da­ta sug­gest­ing the drug, now brand­ed Em­paveli, is just as com­pet­i­tive in the treat­ment-naïve pop­u­la­tion.

Re­port­ing topline re­sults from the Phase III PRINCE study, Apel­lis says Em­paveli beat stan­dard of care as a treat­ment for parox­ys­mal noc­tur­nal he­mo­glo­bin­uria in both he­mo­glo­bin sta­bi­liza­tion and re­duc­tion in lac­tate de­hy­dro­ge­nase af­ter 26 weeks of treat­ment, meet­ing the co-pri­ma­ry end­points. Stan­dard of care, in this con­text, did not in­clude com­ple­ment in­hibitors.

All told, 86% of those treat­ed with Em­paveli were able to avoid a drop of he­mo­glo­bin lev­els above 1 g/dL with­out trans­fu­sions, ver­sus 0% of pa­tients on stan­dard of care (p<0.0001). Mean LDH in the drug group fell by 90% from a base­line of 2151 U/L — which was 9.5 times high­er than the up­per lim­it of nor­mal — com­pared to a 14% re­duc­tion on the con­trol arm (p<0.0001).

The tri­al re­cruit­ed its 53 par­tic­i­pants from Hong Kong, Thai­land, Sin­ga­pore, Malaysia, Philip­pines, Ser­bia, Poland, Pe­ru, Mex­i­co and Colom­bia.

So­bi, the Swedish rare dis­ease com­pa­ny, will be in charge of in­tro­duc­ing Em­paveli to these places, and more, af­ter pay­ing $250 mil­lion up­front to nab ex-US com­mer­cial­iza­tion rights.

Fed­eri­co Grossi

“Com­bined with pre­vi­ous stud­ies, these re­sults em­pha­size the po­ten­tial of Em­paveli to pro­vide dis­ease con­trol for all adults with PNH re­gard­less of pri­or treat­ment,” Fed­eri­co Grossi, Apel­lis CMO, said in a state­ment.

The da­ta were a boost to the broad la­bel Apel­lis al­ready has, wrote Cowen an­a­lyst Phil Nadeau:

Apel­lis sub­mit­ted Em­paveli for FDA ap­proval based on re­sults from the Phase III PE­GA­SUS study in pa­tients who re­mained ane­mic on Soliris, and ini­ti­at­ed the PRINCE study in case the la­bel was ini­tial­ly re­strict­ed to the treat­ment-re­frac­to­ry pa­tient pop­u­la­tion. How­ev­er, Em­paveli’s broad la­bel has made these da­ta sup­port­ive rather than im­per­a­tive; Apel­lis need not sub­mit an sN­DA in or­der for treat­ment-naive pa­tients to be con­sid­ered el­i­gi­ble for treat­ment.

The com­pa­nies added that mean he­mo­glo­bin lev­els in the drug arm in­creased from 9.4 g/dL to 12.1 g/dL, com­pared to a rise of 8.7 g/dL to 9.4 g/dL (p=0.0019). Among those treat­ed with Em­paveli, 91% re­mained trans­fu­sion-free; on­ly 22% in the stan­dard of care group did.

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. Start­ing out in PNH, Apel­lis and So­bi have mapped out broad­er plans in ge­o­graph­ic at­ro­phy, cold ag­glu­tinin dis­ease and hematopoi­et­ic stem cell trans­plan­ta­tion-as­so­ci­at­ed throm­bot­ic mi­croan­giopa­thy.

In the US and Eu­rope, it will soon find it­self go­ing up against As­traZeneca, which has shelled out $39 bil­lion to buy Alex­ion — both up­beat about Soliris’ block­buster sales and the po­ten­tial of fol­low-on drug Ul­tomiris.

While an un­of­fi­cial cross-tri­al com­par­i­son would sug­gest that Em­paveli’s ef­fi­ca­cy is com­pa­ra­ble to both drugs, Nadeau ex­pects it to be used ini­tial­ly by pa­tients who re­main ane­mic on Soliris or Ul­tomiris as it launch­es in­to a PNH mar­ket dom­i­nat­ed by Ul­tomiris.

So­cial: Cedric Fran­cois, Apel­lis CEO (Op­tum via YouTube)

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.

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Div­ing deep­er in­to in­her­it­ed reti­nal dis­or­ders, No­var­tis gob­bles up an­oth­er bite-sized op­to­ge­net­ics biotech

Right about a year ago, a Novartis team led by Jay Bradner and Cynthia Grosskreutz at NIBR swooped in to scoop up a Cambridge, MA-based opthalmology gene therapy company called Vedere. Their focus was on a rather narrow market niche: inherited retinal dystrophies that include a wide range of genetic retinal disorders marked by the loss of photoreceptor cells and progressive vision loss.

But that was just the first deal that whet their appetite.

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FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

The FDA on Monday handed an accelerated approval to Seagen and Genmab’s Tivdak (tisotumab vedotin-tftv, or “TV”) in second-line patients with recurrent or metastatic cervical cancer who previously progressed after chemotherapy rather than PD-(L)1 systemic therapy, the companies said in a release.

Mi­rati's KRAS drug looks like the ear­ly fa­vorite in colon can­cer with new da­ta, putting the pres­sure square on Am­gen

With Amgen already providing proof-of-concept for KRAS inhibitors with its sotorasib, Mirati Therapeutics is piecing together a follow-up effort in lung cancer with data it thinks are superior. But in colon cancer, where solo sotorasib has turned in a dud, Mirati may now have a strong case for superiority.

Mirati’s adagrasib, dosed solo or in combination with chemotherapy cetuximab, showed numerically higher response rates than sotorasib solo and as part of a combination study in a similar patient population also revealed this week at #ESMO21. Mirati’s data were presented as part of a cohort update from the Phase II KRYSTAL-1 study testing adagrasib in a range of solid tumors harboring the KRAS-G12C mutation.

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Ex­elix­is pulls a sur­prise win in thy­roid can­cer just days ahead of fi­nal Cabome­tyx read­out

Exelixis added a thyroid cancer indication to its super-seller Cabometyx’s label on Friday — months before the FDA was expected to make a decision, and days before the company was set to unveil the final data at #ESMO21.

At a median follow-up of 10.1 months, differentiated thyroid cancer patients treated with Cabometyx (cabozantinib) lived a median of 11 months without their disease worsening, compared to just 1.9 months for patients given a placebo, Exelixis said on Monday.