Ernest Loumaye, ObsEva CEO (ObsEva)

Ob­sE­va’s sec­ond uter­ine fi­broids PhI­II comes through, send­ing some in­vestors to the hills

In the three-com­pa­ny race to de­vel­op a new uter­ine fi­broid treat­ment, Ob­sE­va long lagged be­hind Ab­b­Vie and My­ovant. Still, they hoped that bet­ter ef­fi­ca­cy — in­clud­ing a 93.9% re­sponse rate in one Phase III tri­al — could ul­ti­mate­ly de­liv­er bet­ter sales.

Now, though, the sec­ond of those Phase III stud­ies is out, and it has brought the Swedish biotech back to earth.

In the sec­ond of their Phase III tri­als, 75.5% of pa­tients who took Ob­sE­va’s ex­per­i­men­tal tablet lin­zagolix plus a hor­mone saw their bleed­ing re­duced by at least 50% and at least 80 ml af­ter 24 weeks. Pool­ing those re­sults with new da­ta from their first Phase III tri­al — which showed a 93.9% re­sponse rate at 24 weeks and a 91.6% re­sponse rate at 52 weeks — Ob­sE­va cal­cu­lat­ed a col­lec­tive 84.7% re­spon­der rate for pa­tients tak­ing their ther­a­py and said the da­ta “con­firm po­ten­tial best-in-class” sta­tus.

“These ex­cel­lent da­ta move us clos­er to the po­ten­tial com­mer­cial­iza­tion of Ysel­ty and our im­me­di­ate pri­or­i­ty is to progress our reg­u­la­to­ry fil­ings,” Ernest Loumaye, Ob­sE­va CEO and co-founder said in a state­ment, us­ing the brand­ed name for his drug.

Yet some in­vestors and an­a­lysts were dis­ap­point­ed, not­ing that these new re­sults erase the edge that the first tri­al seemed to give Ob­sE­va. 75.5% falls right in line with the re­sults from Ab­b­Vie and My­ovant. Ab­b­vie had a 68.5% re­sponse rate in one Phase III tri­al and a 76.2% re­sponse rate in the sec­ond. My­ovant saw re­sponse rates of 71.2% and 73.4%.

In fact, SVB Leerink’s Ami Fa­dia wrote in a note to in­vestors that be­cause Ob­sE­va had high place­bo re­sponse in both tri­als. the com­pa­ny now has the worst place­bo-ad­just­ed re­sponse of any of the three.

“We be­lieve the place­bo-ad­just­ed re­sponse rate will be a key met­ric that in­vestors pay at­ten­tion to, and the PRIM­ROSE1 re­sults on that mea­sure like­ly fell short of ex­pec­ta­tions,” Fa­dia wrote, not­ing their own Ob­sE­va mod­el is now un­der re­view.

The mar­ket agreed, cut­ting Ob­sE­va’s stock $OB­SV by 40%, or $2.75, Mon­day morn­ing.

Even be­fore the new tri­al, an­a­lysts had ex­pressed reser­va­tions about Ob­sE­va’s ap­par­ent ef­fi­ca­cy. In De­cem­ber, Baird’s Bri­an Sko­r­ney chalked up their high score to a 29.4% place­bo re­sponse rate, far high­er than those seen in their two com­peti­tors’ tri­als. “We think the re­sound­ing take­away here is that the ef­fi­ca­cy pro­files of these 3 … in­hibitors are es­sen­tial­ly the same,” he wrote in a note to in­vestors.

If these drugs are ef­fec­tive­ly the same, Sko­r­ney bet that the first ones out of the gate will es­tab­lish a beach-head and gar­ner the most sales. That would spell bad news for Ob­sE­va. Tim­ing-wise, they now sit in third place. Ab­b­Vie’s drug has al­ready been ap­proved and My­ovant sub­mit­ted an NDA in June, while Ob­sE­va has yet to file an ap­pli­ca­tion. Known as GnRH in­hibitors, these drugs block a hor­mone re­cep­tor in the body.

Some an­a­lysts, though, bet that de­spite some ini­tial con­cerns, safe­ty could ul­ti­mate­ly be Ob­sE­va’s ad­van­tage. When the FDA ap­proved Ab­b­Vie’s drug, Ori­ahnn, they al­so put strict lim­its on its use af­ter mul­ti­ple pa­tients in their tri­al had throm­bot­ic events, in­clud­ing a pul­monary em­bolism. These like­ly came from ex­tra hor­mone treat­ments, known as add-back ther­a­py, pa­tients take to stop the menopause-like symp­toms GnRH in­hibitors can cause.

That’s part­ly why Ob­sE­va in­clud­ed an arm on both tri­als where pa­tients took a small­er dose of the drug and didn’t re­ceive the add-back ther­a­py. In the com­pa­ny’s first tri­al, a lit­tle over half of those pa­tients saw their bleed­ing cut in half. That could make it a good can­di­date for pa­tients with oth­er co-mor­bidi­ties, Fa­dia and oth­er an­a­lysts wrote. The new study showed a 56.6% rate of pa­tients on the no-add-back treat­ment arm, but it al­so had a 35% rate in place­bo, cut­ting the place­bo-ad­just­ed rate to just 21.4%. With new 52-week da­ta out, there were al­so ques­tions about how long the ther­a­py would last.

“We still view the pro­file of both the low dose and the high dose as ap­prov­able,” Fa­dia wrote, “al­though we see po­ten­tial ques­tions com­ing up re­gard­ing the treat­ment du­ra­tion on the la­bel and the com­mer­cial vi­a­bil­i­ty for the low dose.”

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA have vowed not to let politics get in the way of science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped health agencies under his purview — including the FDA — of their rulemaking ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Eli Lilly CSO Dan Skovronsky (file photo)

#ES­MO20: Eli Lil­ly shows off the da­ta for its Verzenio suc­cess. Was it worth $18 bil­lion?

The press release alone, devoid of any number except for the size of the trial, added nearly $20 billion to Eli Lilly’s market cap back in June. Now investors and oncologists will get to see if the data live up to the hype.

On Sunday at ESMO, Eli Lilly announced the full results for its Phase III MonarchE trial of Verzenio, showing that across over 5,000 women who had had HR+, HER2- breast cancer, the drug reduced the odds of recurrence by 25%. That meant 7.8% of the patients on the drug arm saw their cancers return within 2 years, compared with 11.3% on the placebo arm.

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Greg Friberg (File photo)

#ES­MO20: Am­gen team nails down sol­id ear­ly ev­i­dence of AMG 510’s po­ten­tial for NSCLC, un­lock­ing the door to a wave of KRAS pro­grams

The first time I sat down with Amgen’s Greg Friberg to talk about the pharma giant’s KRAS G12C program for sotorasib (AMG 510) at ASCO a little more than a year ago, there was high excitement about the first glimpse of efficacy from their Phase I study, with 5 of 10 evaluable non-small cell lung cancer patients demonstrating a response to the drug.

After decades of failure targeting KRAS, sotorasib offered the first positive look at a new approach that promised to open a door to a whole new approach by targeting a particular mutation to a big target that had remained “undruggable” for decades.

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#ES­MO20: Out to beat Tagris­so, J&J touts 100% ORR for EGFR bis­pe­cif­ic/TKI com­bo — fu­el­ing a quick leap to PhI­II

J&J’s one-two punch on EGFR-mutant non-small cell lung cancer has turned up some promising — although decidedly early — results, fueling the idea that there’s yet room to one up on third-generation tyrosine kinase inhibitors.

Twenty out of 20 advanced NSCLC patients had a response after taking a combination of an in-house TKI dubbed lazertinib and amivantamab, a bispecific antibody targeting both EGFR and cMET engineered on partner Genmab’s platform, J&J reported at ESMO. All were treatment-naïve, and none has seen their cancer progress at a median follow-up of seven months.

Exelixis CEO Michael Morrissey (file photo)

#ES­MO20: Look out Mer­ck. Bris­tol My­ers and Ex­elix­is stake out their com­bo’s claim to best-in-class sta­tus for front­line kid­ney can­cer

Now that the PD-(L)1 checkpoints are deeply entrenched in the oncology market, it’s time to welcome a wave of combination therapies — beyond chemo — looking to extend their benefit to larger numbers of patients. Bristol Myers Squibb ($BMY} and Exelixis {EXEL} are close to the front of that line.

Today at ESMO the collaborators pulled the curtain back on some stellar data for their combination of Opdivo (the PD-1) and Cabometyx (the TKI), marking a significant advance for the blockbuster Bristol Myers franchise while offering a big leg up for the team at Exelixis.

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Dan Skovronsky, Eli Lilly CSO

An­a­lysts are quick to pan Eli Lil­ly's puz­zling first cut of pos­i­tive clin­i­cal da­ta for its Covid-19 an­ti­body

Eli Lilly spotlighted a success for one of 3 doses of their closely-watched Covid-19 antibody drug Wednesday morning. But analysts quickly highlighted some obvious anomalies that could come back to haunt the pharma giant as it looks for an emergency use authorization to launch marketing efforts.

The pharma giant reported that LY-CoV555, developed in collaboration with AbCellera, significantly reduced the rate of hospitalization among patients who were treated with the antibody. The drug arm of the study had a 1.7% hospitalization rate, compared to 6% in the control group, marking a 72% drop in risk.

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#ES­MO20: As­traZeneca aims to spur PRO­found shift in prostate can­cer treat­ment with Lyn­parza OS da­ta

AstraZeneca has unveiled the final, mature overall survival data that cemented Lynparza’s first approval in prostate cancer approval — touting its lead against rivals with the only PARP inhibitor to have demonstrated such benefit.

But getting the Merck-partnered drug to the right patients remains a challenge, something the companies are hoping to change with the new data cut.

The OS numbers on the subgroup with BRCA1/2 or ATM-mutated metastatic castration-resistant prostate cancer are similar to the first look on offer when the FDA expanded the label in May: Lynparza reduced the risk of death by 31% versus Xtandi and Zytiga. Patients on Lynparza lived a median of 19.1 months, compared to 14.7 months for the anti-androgen therapies (p = 0.0175).

#ES­MO20: It’s not just Keytru­da any­more — Mer­ck spot­lights 3 top ear­ly-stage can­cer drugs

Any $12 billion megablockbuster in the portfolio tends to overshadow everything else in the pipeline. Which is something Merck can tell you a little bit about.

Keytruda not only dominates the PD-(L)1 field, it looms over everything Merck does, to the point some analysts wonder if Merck is a one-trick pony.

There’s no shortage of Keytruda data on display at ESMO this weekend, but now the focus is shifting to the future role of new drugs and combos in maintaining that lead position for years to come. And the pharma giant has a special focus for 3 early-stage efforts where Roger Perlmutter’s oncology team is placing some big bets.

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#ES­MO20: Trodelvy da­ta show that Gilead­'s $21B buy­out may have been worth the big pre­mi­um

Gilead CEO Dan O’Day has been on a shopping spree. And while some analysts gawked at the biotech’s recent $21 billion Immunomedics buyout, new data released at virtual ESMO 2020 suggest the acquisition may have been worth the hefty price.

The deal, announced last weekend, will give California-based Gilead $GILD Trodelvy, which was recently approved for metastatic triple-negative breast cancer (mTNBC).

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