Es­pe­ri­on of­fers an­oth­er up­beat cut of piv­otal cho­les­terol da­ta for their com­bo, bumps back read­out for key safe­ty study

Over the past few months Es­pe­ri­on $ES­PR has been grad­u­al­ly dig­ging out of the hole it found it­self in af­ter a small im­bal­ance of deaths in a re­cent cho­les­terol study trig­gered an alarm for some of the an­a­lysts cov­er­ing the com­pa­ny. And the com­pa­ny’s ex­ecs will be keep­ing their fin­gers crossed this morn­ing that in­vestors will re­main sat­is­fied with their lat­est set of Phase III da­ta in the buildup to a mar­ket­ing ap­pli­ca­tion and an­tic­i­pat­ed roll­out next year.

But there are no guar­an­tees for this com­pa­ny, which to­day al­so sig­naled that it is bump­ing back the read­out on its big, piv­otal safe­ty tri­al to Oc­to­ber, push­ing back from a planned show­down next month as Au­gust proved a tough month to get all pa­tients in for their fi­nal vis­it.

Tim Mayleben

Es­pe­ri­on’s sup­port­ing cast on Wall Street can be ex­pect­ed to nod ap­prov­ing­ly as a fixed dose com­bi­na­tion of their be­mpe­doic acid with a shot of Ze­tia hit an added 35% re­duc­tion in LDL (on top of statins) for the on-treat­ment ef­fect at 12 weeks — 32% in the in­tent-to-treat analy­sis. That com­pares to 24% for eze­tim­ibe and 20% for be­mpe­doic acid.

In the ITT analy­sis that scored 21% for Ze­tia and 18% for BA. Place­bo re­spons­es were neg­li­gi­ble, al­low­ing for a com­pelling p val­ue on ef­fi­ca­cy (p=0.001).

But what about safe­ty, where all eyes are on any kind of threat?

Where Es­pe­ri­on got in­to trou­ble in the spring was a slight im­bal­ance in the rate of death be­tween their drug arm and the place­bo group — 13 to 2 — even though none of the deaths were di­rect­ly linked to the drug and no one changed or halt­ed the study. Sta­tis­ti­cal­ly, that may have been noth­ing more than an un­lucky drop of the cards — sta­tis­ti­cal­ly in­signif­i­cant — but Es­pe­ri­on faces its own unique stan­dards on suc­cess that are craft­ed for each hur­dle.

In this lat­est tri­al re­searchers tracked se­ri­ous ad­verse events, but they evened out among the ther­a­peu­tic dos­es, with 8% in the fixed dose arm, 6% for BA, 9% for Ze­tia and 2% in the sug­ar pill arm. But there were no fa­tal­i­ties.

Es­pe­ri­on re­searchers al­so tracked a 34% re­duc­tion in C-re­ac­tive pro­tein for the com­bo — a key safe­ty bio­mark­er though well short of an out­comes ben­e­fit — com­pared to an in­crease in the place­bo group of 4% and re­duc­tions of 20% for BA and 9% for EZE.

“We’re the lipid man­age­ment ex­perts,” says Es­pe­ri­on CEO Tim Mayleben, who sees his chief task right now as ed­u­cat­ing the field on what the da­ta in­di­cate. Priced right, Mayleben and his crew be­lieve that they can make their drug the top choice for mil­lions of pa­tients who don’t do well enough on cheap gener­ic statins but al­so don’t need the full weight of a more ex­pen­sive PC­SK9 drug.

PC­SK9 lead­ers Am­gen, Re­gen­eron and Sanofi, though, are do­ing all they can to un­der­cut that mar­ket, squeez­ing Es­pe­ri­on with low­er prices.

Now in­vestors will be wait­ing un­til Oc­to­ber to find out more about Study 2, which will pro­vide 52-week safe­ty re­sults on a large group of pa­tients. That will set the stage for a mar­ket­ing pitch on both the monother­a­py as well as the com­bi­na­tion, Mayleben tells me. The on­ly oth­er study is its big out­comes study in 2022, which Es­pe­ri­on be­lieves won’t be re­quired ahead of a green reg­u­la­to­ry light.

That still presents a big hur­dle, how­ev­er.

Pay­ers have set a high bar for cho­les­terol drugs, leav­ing Es­pe­ri­on at work try­ing to thread the nee­dle on ef­fi­ca­cy — where PC­SK9 drugs can do bet­ter — and safe­ty, where any hand­i­cap is seen as a po­ten­tial deal killer with in­sur­ers who may well not like the idea of see­ing mil­lions of pa­tients grav­i­tate to a pricey new brand­ed drug.

Their see-saw bat­tle for prov­ing ef­fi­ca­cious enough to al­low the com­pa­ny to shoot for a sweet spot where every­one can be sat­is­fied with a less ex­pen­sive al­ter­na­tive to PC­SK9 will keep the de­bate alive right up un­til the com­pa­ny gets a de­ci­sion on its mar­ket­ing ap­pli­ca­tion. Even af­ter that, the stock could re­main a volatile se­cu­ri­ty.

Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

UP­DAT­ED: Es­ti­mat­ing a US price tag of $5K per course, remde­sivir is set to make bil­lions for Gilead, says key an­a­lyst

Data on remdesivir — the first drug shown to benefit Covid-19 patients in a randomized, controlled trial setting — may be murky, but its maker Gilead could reap billions from the sales of the failed Ebola therapy, according to an estimate by a prominent Wall Street analyst. However, the forecast, which is based on a $5,000-per-course US price tag, triggered the ire of one top drug price expert.