Pfiz­er im­press­es car­dio crowd with mor­tal­i­ty and hos­pi­tal­iza­tion rates for tafamidis in AT­TR-CM -- but Al­ny­lam quick­ly blasts back

Pfiz­er has scored the kind of po­ten­tial­ly game-chang­ing piv­otal da­ta for tafamidis in rare cas­es of transthyretin amy­loid car­diomy­opa­thy that an­a­lysts have been on the look­out for. And the phar­ma gi­ant is rolling out an ex­pand­ed ac­cess pro­gram for AT­TR-CM pa­tients now — just as a ri­val ther­a­py from Al­ny­lam is hit­ting the mar­ket for the first time.

Re­searchers to­day fol­lowed up pos­i­tive top-line da­ta with the news that tafamidis spurred a 30% drop in mor­tal­i­ty risk along with a 32% re­duc­tion in the risk of car­dio-re­lat­ed hos­pi­tal­iza­tion.  That’s good enough to win over a key crowd of top an­a­lysts, but you can bet that there will be plen­ty of ques­tions to­day as every­one hunts for the dev­il in the de­tail. And Al­ny­lam wast­ed no time in rais­ing doubts about the da­ta, which is like­ly go­ing to re­lieve in­vestors fret­ting over the com­pe­ti­tion.

Cred­it Su­isse an­a­lysts ear­li­er not­ed that “even a mod­est im­prove­ment in mor­tal­i­ty (10% to 15%) would be fa­vor­able.” Any­thing 20% to 25% could prove to be a game-chang­er, they added, in a field where a land­mark RNAi ther­a­py from Al­ny­lam is about to hit the mar­ket and an­oth­er — less at­trac­tive — ther­a­py from Akcea and Io­n­is is like­ly right be­hind it.

The da­ta al­so hit a sec­ondary on an im­prove­ment in the re­duc­tion of per­for­mance in the 6-minute walk test along with an im­prove­ment in qual­i­ty of life scores.

But some ques­tions re­main. And at first blush Al­ny­lam got a quick thumbs up for re­main­ing com­pet­i­tive as a mar­ket show­down looms be­tween the lead­ers in the field.

Al­ny­lam fol­lowed up by point­ing out that Pfiz­er looks weak­est where it looks strongest, with­out a sta­tis­ti­cal­ly sig­nif­i­cant read­out for hered­i­tary AT­TR. The com­pa­ny al­so spot­light­ed the pooled dose re­sults, an un­usu­al de­ci­sion by Pfiz­er. They added:

  • In APOL­LO, over 50% of patisir­an pa­tients showed IM­PROVE­MENT rel­a­tive to base­line on both mNIS+7 and Nor­folk.
  • In APOL­LO car­diac sub­pop­u­la­tion of hAT­TR pa­tients*, patisir­an re­sult­ed in:
    • De­crease from base­line (i.e., IM­PROVE­MENT) in NT-proB­NP lev­els (55% re­duc­tion for pati rel­a­tive to pbo)
    • 31.6% of pati pa­tients had de­crease change from base­line of NT-proB­NP ≥30% and ≥300 pg/mL, a key mor­tal­i­ty prog­nos­ti­ca­tor, at Month 18, where­as no pbo pa­tients had de­creas­es of this mag­ni­tude.

Per­haps most sig­nif­i­cant­ly, Al­ny­lam al­so be­lieves that this field is pri­mar­i­ly a growth op­por­tu­ni­ty, as new and bet­ter di­ag­noses iden­ti­fy a grow­ing group of pa­tients for both. In that sce­nario, pa­tients and physi­cians can make their own choic­es as all the biotechs ben­e­fit.

You can get more de­tails in the study pub­lished in the New Eng­land Jour­nal of Med­i­cine.

In­vestors seem fair­ly hap­py ini­tial­ly with both sides. Al­nyam shares jumped 16% by the end of the day — a re­lief ral­ly — while Pfiz­er stock end­ed down a cou­ple of points.

Bren­da Coop­er­stone

Re­searchers of­fered pooled da­ta for two dos­es of the drug — an 80 mg and 20 mg reg­i­men — rather than break­ing the re­sults out in­to dosage groups, leav­ing it un­like­ly that they saw a clear dose re­sponse. An­a­lysts will be fol­low­ing up Pfiz­er’s state­ment to­day with more ques­tions on how the ther­a­py worked. But it’s clear that Pfiz­er will be claim­ing an ad­van­tage here, pro­vid­ing one rea­son for CEO Ian Read’s re­cent vote of con­fi­dence that the com­pa­ny’s late-stage pipeline can pro­vide the big drugs it needs to keep rev­enue on the up­swing.

The drug is al­ready armed with both a break­through ther­a­py des­ig­na­tion as well as a Saki­gake ti­tle from Japan­ese reg­u­la­tors. Look for some quick mar­ket­ing ap­pli­ca­tions and an ag­gres­sive roll­out if the da­ta hold up.

What we al­so didn’t get im­me­di­ate­ly was much de­tail on safe­ty da­ta. The drug arm and place­bo had a “com­pa­ra­ble” safe­ty pro­file, the com­pa­ny re­port­ed.

Cred­it Su­isse has es­ti­mat­ed peak sales at $600 mil­lion, with a shot at more un­der cer­tain cir­cum­stances. The big ques­tion now is how much Al­ny­lam — whose drug On­pat­tro was ap­proved for TTR polyneu­ropthay — might be af­fect­ed by the com­pe­ti­tion. Ac­cord­ing to the an­a­lysts:

Though the in­di­ca­tions may be dif­fer­ent, the prod­ucts will like­ly com­pete, as physi­cians we spoke with in­di­cat­ed that many pa­tients with car­diomy­opa­thy tend to al­so have polyneu­ropa­thy and vice ver­sa. A few physi­cians be­lieve Al­ny­lam’s prod­uct is the safer prod­uct and will use patisir­an to treat car­diomy­opa­thy while get­ting re­im­burse­ment for polyneu­ropa­thy. Oth­er physi­cians ex­pect to pri­mar­i­ly pre­scribe tafamidis if the out­come da­ta are clin­i­cal­ly mean­ing­ful.

Pfiz­er, though, al­so faces a chal­lenge in get­ting physi­cians to do a much bet­ter job at di­ag­nos­ing TTR-car­diomy­opa­thy. But their de­ci­sion to be­gin a wide-open ex­pand­ed ac­cess pro­gram is a clear shot over Al­ny­lam’s bow. The drug is al­ready ap­proved as Vyn­daqel and on the mar­ket to treat fa­mil­ial amy­loid polyneu­ropa­thy.

Their mar­ket ri­val­ry starts to­day.

Al­so af­fect­ed by to­day’s an­nounce­ment is Ei­dos Ther­a­peu­tics $EI­DX, which re­cent­ly went pub­lic as it pur­sued its own work in the field.

“We be­lieve the AT­TR-ACT study find­ings bring us a sig­nif­i­cant step clos­er to our goal of pro­vid­ing an ur­gent­ly need­ed ther­a­py for a se­ri­ous and of­ten fa­tal dis­ease,” said Bren­da Coop­er­stone, Pfiz­er’s chief de­vel­op­ment of­fi­cer for rare dis­ease. “We look for­ward to con­tin­u­ing dis­cus­sions with glob­al reg­u­la­to­ry au­thor­i­ties about the po­ten­tial of tafamidis as a treat­ment op­tion for peo­ple liv­ing with AT­TR-CM.” 

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

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

You may start to notice more stories exclusively available to Premium subscribers. This week alone, paid subscribers can read our in-depth reporting on Alzheimer’s data, digital therapeutics and Allogene’s cell therapy for solid tumors, as well as scoops on Twitter ads and Catalent. With your support, we can keep growing our team and spend more time on quality work. We have both individual and company plans available — check them out to unlock the full Endpoints experience.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 154,000+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 154,000+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints Premium

Premium subscription required

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

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 154,000+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 154,000+ biopharma pros reading Endpoints daily — and it's free.

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.