Durable, safe and ef­fec­tive long-term kid­ney drug da­ta from Tri­ci­da fu­el block­buster po­ten­tial

Kid­ney drug de­vel­op­er Tri­ci­da’s shares shot up on Thurs­day, af­ter long-term da­ta high­light­ed its lead drug’s durable ef­fi­ca­cy and safe­ty pro­file as a treat­ment for meta­bol­ic aci­do­sis, in which faulty kid­neys are not able to ex­pel the acid caus­ing a buildup in the body.

The drug — TRC101 — is de­signed to bind to hy­drochlo­ric acid in the GI tract, trig­ger­ing the ejec­tion of acid via ex­cre­tion — there­by di­min­ish­ing acid lev­els and stim­u­lat­ing blood bi­car­bon­ate. The com­pa­ny ex­pects to sub­mit an ap­pli­ca­tion to mar­ket the drug by the sec­ond half of this year for the con­di­tion com­mon­ly caused by chron­ic kid­ney dis­ease (and be­lieved to ac­cel­er­ate the pro­gres­sion of CKD), in­crease the risk of mus­cle wast­ing and cause the loss of bone den­si­ty. If ap­proved, it will be the first drug to win the FDA nod specif­i­cal­ly for meta­bol­ic aci­do­sis.

Ger­rit Klaern­er

Da­ta post­ed last June showed the drug in­duced a sta­tis­ti­cal­ly sig­nif­i­cant in­crease in blood bi­car­bon­ate in 208 pa­tients af­ter 12 weeks in a Phase III study, hours af­ter the com­pa­ny ad­ver­tised plans to go pub­lic in a $150 mil­lion IPO. On Thurs­day, Tri­ci­da re­vealed da­ta from a 40-week ex­ten­sion to that study in the 185 pa­tients that com­plet­ed one year as part of the tri­al.

The drug met all the pri­ma­ry and sec­ondary goals of the ex­ten­sion por­tion of the tri­al. The main goal of the ex­ten­sion study was the as­sess­ment of the long-term safe­ty pro­file of TRC101 ver­sus place­bo — and da­ta showed 2.6% of the pa­tients on TRC101 ver­sus 9.8% on place­bo dis­con­tin­ued the 40-week treat­ment pe­ri­od pre­ma­ture­ly.

Sig­nif­i­cant­ly, da­ta on the drug’s dura­bil­i­ty were al­so pos­i­tive. Over 52 weeks, 63% of the 111 TRC101-treat­ed pa­tients ex­hib­it­ed an in­crease in blood bi­car­bon­ate lev­el of at least 4 mil­liequiv­a­lents per liter, or achieved a blood bi­car­bon­ate lev­el in the nor­mal range — com­pared to 38% of the 74 place­bo sub­jects (p=0.0015).

The sta­tis­ti­cal plan al­so called for the eval­u­a­tion of TRC101 ver­sus place­bo for the com­pos­ite end­point of: all-cause mor­tal­i­ty, dial­y­sis/kid­ney trans­plant or a ≥50% de­cline in es­ti­mat­ed glomeru­lar fil­tra­tion rate (a test used to check how well the kid­neys are work­ing) — DD50 when tak­en to­geth­er — over the 52 week pe­ri­od. Of the 124 sub­jects giv­en TRC101, 4% (5) had a DD50 event, in­clud­ing one pa­tient who ini­ti­at­ed dial­y­sis. In con­trast, of the 93 sub­jects ran­dom­ized to the place­bo group, 10.8% (10) sub­jects had a DD50 event, in­clud­ing four deaths and one who ini­ti­at­ed dial­y­sis.

While the tri­al was not pow­ered to as­sess all-cause mor­tal­i­ty and/or the pro­gres­sion of CKD out­comes, Tri­ci­da said it ob­served a 65% re­duc­tion in the an­nu­al­ized event rate of the com­pos­ite end­point of all-cause mor­tal­i­ty and/or the pro­gres­sion of CKD in TRC101-treat­ed sub­jects ver­sus the place­bo group.

“The 52-week…re­sults far ex­ceed­ed our ex­pec­ta­tions,” said com­pa­ny chief Ger­rit Klaern­er said in a state­ment. “We did not an­tic­i­pate that we would ob­serve ev­i­dence of clin­i­cal ben­e­fit be­yond the in­crease in blood bi­car­bon­ate in pa­tients treat­ed with TRC101 un­til the read out of the re­sults of our post­mar­ket­ing tri­al…in the 2022 to 2023 time­frame.”

Shares of the South San Fran­cis­co-based drug de­vel­op­er $TC­DA leapt more than 57% on Thurs­day, clos­ing at $37.80.

Cowen’s Phil Nadeau, who deemed the da­ta ‘im­pres­sive,’ ex­pects TRC101 will achieve $1 bil­lion in rev­enue by 2025.

(T)here is a ma­jor need to con­trol meta­bol­ic aci­do­sis and slow the pro­gres­sion of CKD. Though sodi­um bi­car­bon­ate is ef­fec­tive, its high sodi­um con­cen­tra­tion makes most CKD pa­tients in­el­i­gi­ble for it…With 25 mil­lion peo­ple in the U.S. hav­ing stage 3, 4, or 5 CKD, TRC101 al­so ad­dress­es a large pa­tient pop­u­la­tion, and even mod­est pen­e­tra­tion could yield bil­lions in sales.

(T)he com­pos­ite end­point da­ta com­bined with the phys­i­cal func­tion­ing scores show clear, clin­i­cal­ly mean­ing­ful ben­e­fits to pa­tients. In fact, the dra­mat­ic re­duc­tion in the com­pos­ite end­point im­plies that physi­cians need to treat at most 3 pa­tients in or­der for 1 to de­rive a clin­i­cal­ly mean­ing­ful re­duc­tion in CKD pro­gres­sion.

Sep­a­rate­ly, Tri­ci­da on Thurs­day said it had amend­ed its debt fa­cil­i­ty with Her­cules Cap­i­tal, rais­ing the to­tal amount avail­able to up to $200 mil­lion from the $100 mil­lion agreed in Feb­ru­ary 2018.

John Hood [file photo]

UP­DATE: Cel­gene and the sci­en­tist who cham­pi­oned fe­dra­tinib's rise from Sanofi's R&D grave­yard win FDA OK

Six years after Sanofi gave it up for dead, the FDA has approved the myelofibrosis drug fedratinib, now owned by Celgene.

The drug will be sold as Inrebic, and will soon land in the portfolio at Bristol-Myers Squibb, which is finalizing a deal to acquire Celgene.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: AveX­is sci­en­tif­ic founder was axed — and No­var­tis names a new CSO in wake of an ethics scan­dal

Now at the center of a storm of controversy over its decision to keep its knowledge of manipulated data hidden from regulators during an FDA review, Novartis CEO Vas Narasimhan has found a longtime veteran in the ranks to head the scientific work underway at AveXis, where the incident occurred. And the scientific founder has hit the exit.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

Ab­b­Vie gets its FDA OK for JAK in­hibitor upadac­i­tinib, but don’t look for this one to hit ex­ecs’ lofty ex­pec­ta­tions

Another big drug approval came through on Friday afternoon as the FDA OK’d AbbVie’s upadacitinib — an oral JAK1 inhibitor that is hitting the rheumatoid arthritis market with a black box warning of serious malignancies, infections and thrombosis reflecting fears associated with the class.

It will be sold as Rinvoq — at a wholesale price of $59,000 a year — and will likely soon face competition from a drug that AbbVie once controlled, and spurned. Reuters reports that a 4-week supply of Humira, by comparison, is $5,174, adding up to about $67,000 a year.

The top 10 fran­chise drugs in bio­phar­ma his­to­ry will earn a to­tal of $1.4T (tril­lion) by 2024 — what does that tell us?

Just in case you were looking for more evidence of just how important Amgen’s patent win on Enbrel is for the company and its investors, EvaluatePharma has come up with a forward-looking consensus estimate on what the list of top 10 drugs will look like in 2024.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Sci­en­tist-CEO ac­cused of im­prop­er­ly us­ing con­fi­den­tial in­fo from uni­corn Alec­tor

The executive team at Alector $ALEC has a bone to pick with scientific co-founder Asa Abeliovich. Their latest quarterly rundown has this brief note buried inside:

On June 18, 2019, we initiated a confidential arbitration proceeding against Dr. Asa Abeliovich, our former consulting co-founder, related to alleged breaches of his consulting agreement and the improper use of our confidential information that he learned during the course of rendering services to us as our consulting Chief Scientific Officer/Chief Innovation Officer. We are in the early stage of this arbitration proceeding and are unable to assess or provide any assurances regarding its possible outcome.

There’s no explicit word in the filing on what kind of confidential info was involved, but the proceeding got started 2 days ahead of Abeliovich’s IPO.

Abeliovich, formerly a tenured associate professor at Columbia, is a top scientist in the field of neurodegeneration, which is where Alector is targeted. More recently, he’s also helped start up Prevail Therapeutics as the CEO, which raised $125 million in an IPO. And there he’s planning on working on new gene therapies that target genetically defined subpopulations of Parkinson’s disease. Followup programs target Gaucher disease, frontotemporal dementia and synucleinopathies.

But this time Abeliovich is the CEO rather than a founding scientist. And some of their pipeline overlaps with Alector’s.

Abeliovich and Prevail, though, aren’t taking this one lying down.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

Chi­na has be­come a CEO-lev­el pri­or­i­ty for multi­na­tion­al phar­ma­ceu­ti­cal com­pa­nies: the trend and the im­pli­ca­tions

After a “hot” period of rapid growth between 2009 and 2012, and a relatively “cooler” period of slower growth from 2013 to 2015, China has once again become a top-of-mind priority for the CEOs of most large, multinational pharmaceutical companies.

At the International Pharma Forum, hosted in March in Beijing by the R&D Based Pharmaceutical Association Committee (RDPAC) and the Pharmaceutical Research and Manufacturers of America (PhRMA), no fewer than seven CEOs of major multinational pharmaceutical firms participated, including GSK, Eli Lilly, LEO Pharma, Merck KGaA, Pfizer, Sanofi and UCB. A few days earlier, the CEOs of several other large multinationals attended the China Development Forum, an annual business forum hosted by the research arm of China’s State Council. It’s hard to imagine any other country, except the US, having such drawing power at CEO level.

As dis­as­ter struck, Ab­b­Vie’s Rick Gon­za­lez swooped in on Al­ler­gan with an of­fer Brent Saun­ders couldn’t say no to

Early March was a no good, awful, terrible time for Allergan CEO Brent Saunders. His big lead drug had imploded in a Phase III disaster and activists were after his hide — or at least his chairman’s title — as the stock price continued a steady droop that had eviscerated share value for investors.

But it was a perfect time for AbbVie CEO Rick Gonzalez to pick up the phone and ask Saunders if he’d like to consider a “strategic” deal.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

CEO Pascal Soriot via Getty Images

As­traZeneca's jug­ger­naut PARP play­er Lyn­parza scoops up an­oth­er dom­i­nant win in PhI­II as the FDA adds a 'break­through' for Calquence

AstraZeneca’s oncology R&D group under José Baselga keeps churning out hits.

Wednesday morning the pharma giant and their partners at Merck parted the curtains on a successful readout for their Phase III PAOLA-1 study, demonstrating statistically significant improvement in progression-free survival for women with ovarian cancer in a first-line maintenance setting who added their PARP Lynparza to Avastin. This is their second late-stage success in ovarian cancer, which will help stave off rivals like GSK.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

ICER blasts FDA, PTC and Sarep­ta for high prices on DMD drugs Em­flaza, Ex­ondys 51

ICER has some strong words for PTC, Sarepta and the FDA as the US drug price watchdog concludes that as currently priced, their respective new treatments for Duchenne muscular dystrophy are decidedly not cost-effective.

The final report — which cements the conclusions of a draft issued in May — incorporates the opinion of a panel of 17 experts ICER convened in a public meeting last month. It also based its analysis of Emflaza (deflazacort) and Exondys 51 (eteplirsen) on updated annual costs of $81,400 and over $1 million, respectively, after citing “incorrect” lower numbers in the initial calculations.