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.” 

89bio said its drug was better than placebo at lessening fibrosis without worsening nonalcoholic steatohepatitis, or NASH, in two of three dose groups.

The San Francisco biotech said it thinks the Phase IIb data pave the way for a potential Phase III, following in the footsteps of another biotech in its drug class, Akero Therapeutics. To fund a late-stage study, CEO Rohan Palekar told Endpoints News 89bio “would need to raise additional capital,” with the company having about $188 million at the end of last year.