#AS­CO18: Ab­b­Vie con­vinces one top an­a­lyst that its $6B 'megablock­buster' Ro­va-T is worth­less

Ab­b­Vie $AB­BV has man­aged to con­vince at least one promi­nent an­a­lyst that Ro­va-T is ab­solute­ly worth­less, as the com­pa­ny’s vi­sion of a $5 bil­lion earn­er grad­u­al­ly dis­solves.

Ge­of­frey Porges, Leerink

Ge­of­frey Porges at Leerink took a look at Ab­b­Vie’s for­mal pre­sen­ta­tion of its Trin­i­ty tri­al da­ta at AS­CO and came away shak­ing his head. His con­clu­sion:

The re­sults shown in the pre­sen­ta­tion were even worse than we had feared, and al­though Ab­b­Vie’s stock sold off much more than the val­ue of Ro­va- T af­ter the an­nounce­ment, we can’t help but re­gard the on­go­ing tri­als as large­ly fruit­less ex­er­cis­es. Fur­ther­more, the tox­i­c­i­ty sig­nal from the tri­al, along with the rel­a­tive­ly mar­gin­al ef­fi­ca­cy sig­nal, jus­ti­fies the com­plete elim­i­na­tion of all rev­enue as­so­ci­at­ed with Ro­va-T from our com­pa­ny fore­cast and val­u­a­tion for Ab­b­Vie. 

There was a lot to dis­like about the da­ta, he says, in­clud­ing the high 34% dis­con­tin­u­a­tion rate in the study; “49 or these 116 pre­ma­ture dis­con­tin­u­a­tions were due to pro­gres­sive dis­ease, with the oth­ers be­ing due to ad­verse events or oth­er undis­closed rea­sons.”

For the pri­ma­ry end­point over re­sponse rate, mea­sured by change in the tar­get le­sion, of the 301 evalu­able pa­tients (pre­sum­ably the oth­er 38 pa­tients were de­ceased or lost to fol­low up), the in­ves­ti­ga­tor-mea­sured re­sponse rate was 18%, in­creas­ing mod­est­ly to 19.7% in the DLL3 high group.

As mea­sured by the in­de­pen­dent re­view board,  the re­sponse rate fell to 12.4% for the com­bined pop­u­la­tion, and 14.3% in the DLL3-high pa­tients. And se­ri­ous ad­verse events in the drug group ran high.

Ab­b­Vie paid $5.8 bil­lion in cash for this drug, promis­ing up to $4 bil­lion more in mile­stones to ac­quire the lit­tle-known biotech uni­corn Stem­cen­trx. And with mon­ey like that on the ta­ble, ex­pec­ta­tions were run­ning high, fu­el­ing fore­casts that the phar­ma com­pa­ny could get past the even­tu­al loss of patent pro­tec­tion on Hu­mi­ra in style. Ab­b­Vie it­self pro­ject­ed peak sales at $5 bil­lion a year.

Porges’ con­clu­sion: The drug and the class look dead on ar­rival at AS­CO.

Ul­ti­mate­ly it seems un­like­ly in our view that Ro­va-T, or per­haps any vari­ant of DLL3 an­ti­body-drug con­ju­gate med­i­cine, will come to mar­ket, at least while the pro­file looks the way it did in TRIN­I­TY.

Con­quer­ing a silent killer: HDV and Eiger Bio­Phar­ma­ceu­ti­cals

Hepatitis delta, also known as hepatitis D, is a liver infection caused by the hepatitis delta virus (HDV) that results in the most severe form of human viral hepatitis for which there is no approved therapy.

HDV is a single-stranded, circular RNA virus that requires the envelope protein (HBsAg) of the hepatitis B virus (HBV) for its own assembly. As a result, hepatitis delta virus (HDV) infection occurs only as a co-infection in individuals infected with HBV. However, HDV/HBV co-infections lead to more serious liver disease than HBV infection alone. HDV is associated with faster progression to liver fibrosis (progressing to cirrhosis in about 80% of individuals in 5-10 years), increased risk of liver cancer, and early decompensated cirrhosis and liver failure.
HDV is the most severe form of viral hepatitis with no approved treatment.
Approved nucleos(t)ide treatments for HBV only suppress HBV DNA, do not appreciably impact HBsAg and have no impact on HDV. Investigational agents in development for HBV target multiple new mechanisms. Aspirations are high, but a functional cure for HBV has not been achieved nor is one anticipated in the forseeable future. Without clearance of HBsAg, anti-HBV investigational treatments are not expected to impact the deadly course of HDV infection anytime soon.

UP­DAT­ED: In a land­mark first glimpse of hu­man da­ta from Ver­tex, CRISPR/Cas9 gene ther­a­py sig­nals ear­ly ben­e­fit

Preliminary data on two patients with blood disorders that have been administered with Vertex and partner CRISPR Therapeutics’ gene-editing therapy suggest the technology is safe and effective, marking the first instance of the benefit of the use of CRISPR/Cas9 technology in humans suffering from disease.

Patients in these phase I/II studies give up peripheral blood from which hematopoietic stem and progenitor cells are isolated. The cells are tinkered with using CRISPR/Cas9 technology, and the edited cells — CTX001 — are infused back into the patient via a stem cell transplant. The objective of CTX001 is to fix the errant hemoglobin gene in patents with two blood disorders: beta-thalassemia and sickle cell disease, by unleashing the production of fetal hemoglobin.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 66,000+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Make that 2 ap­proved RNAi drugs at Al­ny­lam af­ter the FDA of­fers a speedy OK on ul­tra-rare dis­ease drug

Seventeen years into the game, Alnylam’s pivot into commercial operations is picking up speed.
The bellwether biotech $ALNY has nabbed their second FDA OK for an RNAi drug, this time for givosiran, the only therapy now approved for acute hepatic porphyria. This second approval came months ahead of the February deadline — even after winning priority review following their ‘breakthrough’ title earlier.
AHP is an extremely rare disease, with some 3,000 patients in Europe and the US, not all diagnosed, and analysts have projected peak revenue of $600 million to $700 million a year. The drug will be sold as Givlaari.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 66,000+ biopharma pros reading Endpoints daily — and it's free.

David Ricks. Eli Lilly

Eli Lil­ly touts $400M man­u­fac­tur­ing ex­pan­sion, 100 new jobs to much fan­fare in In­di­anapo­lis — even though it's been chop­ping staff

Eli Lilly is pouring in $400 million to beef up manufacturing facilities at its home base of Indianapolis. The investment, which was lauded by the city’s mayor, is expected to create 100 new jobs.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 66,000+ biopharma pros reading Endpoints daily — and it's free.

Am­gen chops 172 more staffers in R&D, op­er­a­tions and sales amid neu­ro­science ex­it, rev­enue down­turn

Neuroscience wasn’t the only unit that’s being hit by a reorganization underway at Amgen. As well as axing 149 employees in its Cambridge office, the company has disclosed that 172 others nationwide, including some from its Thousand Oaks, CA headquarters, are being let go.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 66,000+ biopharma pros reading Endpoints daily — and it's free.

Stephen Hahn (via Senate HELP Committee)

Stephen Hahn gets through Sen­ate’s soft­ball job in­ter­view — but most­ly plays dodge­ball on the is­sues fac­ing the FDA

Anyone looking for fresh insights on what kind of FDA commissioner Stephen Hahn will be got precious few clues during Wednesday’s Senate hearing on the nomination.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Op­di­vo/Yer­voy com­bo for melanoma fails in key pa­tient pop­u­la­tion

Bristol-Myers Squibb’s efforts to expand their checkpoint inhibitor combination have run into another recalcitrant cancer.

The NJ-based pharma announced that a combination of Yervoy and Opdivo didn’t beat out Opdivo alone in patients with resected high-risk melanoma who had very low levels of PD-L1. The drug combo couldn’t improve recurrence-free survival in these post-surgery patients.

Ver­tex's stel­lar quar­ter car­ries on with French re­im­burse­ment deal

Vertex’s golden quarter just got brighter. About a month after the US drugmaker finally clinched a deal with UK authorities to cover its slate of cystic fibrosis (CF) drugs following years of protracted negotiations, the company on Wednesday secured a deal with France for its CF therapy, Orkambi.

After the UK, France has one of the largest CF populations outside the United States. Achieving French reimbursement unlocks an ~7000-patient CF population, around ~2500-3000 of which will likely be eligible to receive (and be reimbursed for) Orkambi, Stifel’s Paul Matteis wrote in a note.

Nello Mainolfi, Kymera via Youtube

Kymera hands the helm to No­var­tis vet — and found­ing CSO — Nel­lo Main­olfi

Kymera Therapeutics is turning to a co-founder to run the company.
The protein degradation specialist with a deep-pocket syndicate behind them has opted to give the helm officially to Nello Mainolfi. The new CEO is a veteran of the Novartis Institutes for Biomedical Research. He joined Atlas Venture in their entrepreneur-in-residence program and helped launch Kymera as the CSO three years ago with Atlas’ Bruce Booth.
The boast at Kymera is that they’re angling to create a new class of protein degraders, a popular field where there’s been a variety of startups. One of its chief advocates is NIBR head Jay Bradner, who launched C4 just ahead of joining Novartis, where he’s also been doing new work in the field.