Es­ca­lat­ing R&D woes spur fresh M&A chat­ter for cash-rich Gilead

Gilead CSO Nor­bert Bischof­berg­er

Four years af­ter Gilead ac­quired mo­melo­tinib in its $510 mil­lion buy­out of YM Bio­Sciences, the big — and what ap­pears to be in­creas­ing­ly un­lucky — biotech was forced to re­port that the drug per­formed poor­ly in its two Phase III myelofi­bro­sis tri­als. And the fourth straight pipeline flop quick­ly spurred fresh spec­u­la­tion that Gilead will soon have to tap in­to its big cash re­serves for a ma­jor ac­qui­si­tion.

The JAK in­hibitor scored on a non-in­fe­ri­or­i­ty show­down with Jakafi (In­cyte’s rux­oli­tinib) in spleen re­duc­tion, but blew the key sec­ondary end­point of non-in­fe­ri­or­i­ty for the to­tal symp­tom score that was used to mea­sure the drugs. And it failed a sep­a­rate Phase III su­pe­ri­or­i­ty com­par­i­son against best avail­able treat­ment at week 24.

It all adds up to a fresh pipeline mess at Gilead, which saw its shares $GILD de­cline 1.25% Thurs­day morn­ing, shav­ing off more than a bil­lion dol­lars of its $100 bil­lion mar­ket cap. In­cyte {IN­CY}, mean­while, saw its shares shoot up 7% on the news, as spec­u­la­tion mount­ed that Gilead may now be pressed hard to make a bid for the com­pa­ny.

By the num­bers: mo­melo­tinib: 6.7%; BAT: 5.8%; 95 per­cent CI: -8.9% to +10.2%; p=0.90. And be­cause it didn’t suc­ceed on su­pe­ri­or­i­ty on the pri­ma­ry score, in­ves­ti­ga­tors didn’t run the num­bers on sec­ondary end­points.

That’s not what the com­pa­ny want­ed or need­ed to see. But af­ter high­light­ing some pos­i­tive trends from the two late-stage stud­ies, Gilead plans to see if reg­u­la­tors are feel­ing gen­er­ous about its prospects.

“The re­sults from both the SIM­PLI­FY-1 and SIM­PLI­FY-2 stud­ies in­di­cate that mo­melo­tinib pro­vides some treat­ment ben­e­fit, in­clud­ing ben­e­fit on ane­mia-re­lat­ed end­points,” said Nor­bert Bischof­berg­er, PhD, Ex­ec­u­tive Vice Pres­i­dent of Re­search and De­vel­op­ment and Chief Sci­en­tif­ic Of­fi­cer. “We plan to dis­cuss these re­sults with reg­u­la­to­ry au­thor­i­ties to de­ter­mine the next steps.”

The set­back on mo­melo­tinib comes near the end of what has turned in­to a grim year for Gilead. A re­cent run­down of its work on the NASH drug GS-4997 sparked con­sid­er­able skep­ti­cism from an­a­lysts, who want to see much more com­pelling num­bers be­fore they buy in.

Gilead re­cent­ly wrote off sim­tuzum­ab, along with the late-stage drug GS-5745 for ul­cer­a­tive col­i­tis and Crohn’s. And it’s top car­dio prospect — ele­clazine (GS-6615) — failed a late-stage study as well, sig­nif­i­cant­ly re­duc­ing its chances of be­com­ing the big new drug that Gilead needs as hep C wanes.

As the R&D hole keeps get­ting deep­er, some won­der if Gilead will be forced back to the deal ta­ble to buy some­thing big. Its hep C fran­chise may be wan­ing, but it cre­at­ed a huge wind­fall in cash re­serves. And Leerink’s Ge­of­frey Porges be­lieves that this lat­est black cloud comes with a sil­ver lin­ing, adding In­cyte to the list of big takeover tar­gets. On Thurs­day morn­ing he not­ed:

GILD in­di­cat­ed that they plan to dis­cuss these re­sults with reg­u­la­to­ry au­thor­i­ties to de­ter­mine the next steps, but it seems like­ly that mo­melo­tinib, which has been in de­vel­op­ment since 2009, will be writ­ten off, end­ing the po­ten­tial of yet an­oth­er small “bolt on” ac­qui­si­tion. One con­se­quence of this dis­ap­point­ment, how­ev­er, is that it does re­store IN­CY to the list of fea­si­ble can­di­dates for ac­qui­si­tion by Gilead, since they would no longer face the oblig­a­tion to di­vest one of the over­lap­ping JAK pro­grams.

Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Big week for Alzheimer’s da­ta; As­traZeneca buys cell ther­a­py start­up; Dig­i­tal ther­a­peu­tics hits a pay­er wall; and more

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Am­gen, years be­hind ri­vals, says PhI obe­si­ty drug shows dura­bil­i­ty signs

While NBC ran “The Biggest Loser” for 17 seasons, deemed toxic by critics for the reality show’s punishing exercise and diet upheavals, researchers in pharmaceutical labs have been attempting to create prescription drugs that induce weight loss — and one pharma betting it can require less frequent dosing is out with a new crop of data.

Amgen was relatively late to the game compared to its approved competitor Novo Nordisk and green light-approaching rival Eli Lilly. But early data suggested Amgen’s AMG 133 led to a 14.5% weight reduction in the first few months of dosing, buoying shares earlier this fall, and now the California pharma is out with its first batch of durability data showing that figure fell slightly to 11.2% about 150 days after the last dose. Amgen presented at the 20th World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease on Saturday afternoon.

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Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls

Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

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Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

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US month­ly costs for biosim­i­lars 'sub­stan­tial­ly high­er' than Ger­many or Switzer­land, JA­MA re­search finds

As the global biologics market is expected to hit nearly the half-trillion-dollar mark this year, new JAMA research points to the importance of timely biosimilar entry, particularly as fewer biosimilars are entering the US than in Europe, and as monthly treatment costs for biosimilars were “substantially higher” in the US compared with Germany and Switzerland.

Among the three countries, biosimilar market share at launch was highest in Germany, but increased at the fastest rate in the US, the authors from the University of Zurich’s Institute of Law wrote in JAMA Network Open today.

Kirk Myers is shown in a still image from a new film series showcasing the efforts of HIV advocates funded by Gilead.

Gilead spot­lights HIV projects and the com­mu­ni­ty lead­ers dri­ving them in new mi­ni-doc­u­men­tary films

Gilead is going behind the scenes of some of the HIV initiatives it funds through grants in a new film series narrated by the people helming the projects.

The first four films and leaders come from across the US — Arianna Lint in Florida and Puerto Rico, Cleve Jones in San Francisco, June Gipson in Mississippi and Kirk Myers in Texas. Their HIV-focused efforts range from addressing unmet needs of the transgender community to delivering social services and high-quality health care in underserved communities.

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EMA pulls an opi­oid from the 1950s used to treat dry cough

The European Medicines Agency said Friday that it’s pulling from all European markets pholcodine-containing medicines, which are an opioid used in adults and children for the treatment of dry cough and in combo with other drugs as a treatment for cold and flu.

The decision to pull the medicines comes as the EMA points to the results from the recent ALPHO study, which show that use of pholcodine during the 12 months preceding anesthesia is linked to a risk of an anaphylactic reaction related to the neuromuscular blocking agents (NMBAs) used (with an adjusted OR of 4.2, and a 95% confidence interval of 2.5 to 6.9).

David Arthur, Salarius Pharmaceuticals CEO

Salarius Phar­ma­ceu­ti­cals sees with­drawals, 3 of 13 pa­tient re­spon­ders in sar­co­ma tri­al

The Houston-based biotech Salarius Pharmaceuticals is lifting the cover on data from a Phase I/II trial for a drug currently on voluntary hold after a patient death, and the results appear to have underwhelmed investors.

Salarius’ candidate, dubbed seclidemstat, is an oral LSD1 inhibitor that is meant to treat Ewing sarcoma and FET-rearranged sarcomas in patients under 12 years old. The biotech had presented data with 13 patients with “first- and second-relapse Ewing sarcoma” who were treated in combination with topotecan and cyclophosphamide.