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.” 

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

FDA chief Stephen Hahn on Capitol Hill earlier this week (Getty Images)

As FDA buck­les un­der the strain of a pan­dem­ic work­load, Trump again ac­cus­es the agency of a po­lit­i­cal hit job

Peter Marks appeared before a virtual SVB Leerink audience yesterday and said that his staff at FDA’s CBER is on the verge of working around the clock. Manufacturing inspections, policy work and sponsor communications have all been pushed down the to-do list so that they can be responsive to Covid-related interactions. And the agency’s objective right now? “To save as many lives as we can,” Marks said, likening the mortality on the current outbreak as equivalent to “a nuclear bomb on a small city.”

Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

Play-by-play of Gilead­'s $21B Im­munomedics buy­out de­tails a fren­zied push — and mints a new biotech bil­lion­aire

Immunomedics had not really been looking for a buyout when the year began. Excited by its BLA for Trodelvy, submitted to the FDA in late 2019, executive chairman Behzad Aghazadeh started off looking for potential licensing deals and zeroed in on four potential partners, including Gilead, following January’s JP Morgan Healthcare Conference in San Francisco. Such talks advanced throughout the year, with discussions advancing to the second round in mid-August.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 90,500+ biopharma pros reading Endpoints daily — and it's free.

The win­dow is wide open as four more biotechs join the go-go IPO class of 2020

It’s another day of hauling cash in the biopharma world as four more IPOs priced Friday and a fifth filed its initial paperwork.

The biggest offering comes from PMV Pharma, an oncology biotech focusing on p53 mutations, which raised $211.8 million after pricing shares at $18 apiece. Prelude Therapeutics, developing PRMT5 inhibitors for rare cancers, was next with a $158 million raise, pricing shares at $19 each. Graybug Vision raised $90 million after pricing at $16 per share for its wet AMD candidates, and breast cancer biotech Greenwich Lifesciences brought up the rear with a small, $7 million raise after pricing shares at $5.75.

J&J of­fers PhI/IIa da­ta show­ing its sin­gle-dose vac­cine can stir up suf­fi­cient im­mune re­sponse

Days after J&J dosed the first participants of its Phase III ENSEMBLE trial, the pharma giant has detailed the early-stage data that gave them confidence in a single-dose regimen.

Testing two dose levels either as a single dose or in a two-dose schedule spaced by 56 days in, the scientists from Janssen, the J&J subsidiary developing its vaccine, reported that the low dose induced a similar immune response as the high dose. The interim Phase I/IIa results were posted in a preprint on medRxiv.

President Donald Trump reacts after signing an executive order following his remarks on his healthcare policies yesterday in Charlotte, North Carolina (Getty Images)

Op-ed: Will phar­ma re­al­ly pay for Trump’s lat­est law­less promise to 33 mil­lion Medicare ben­e­fi­cia­ries? Not like­ly

Sitting atop the executive branch, President Donald Trump is the ultimate authority at the FDA. He can fast track any vaccine to approval himself. If it came to that, of course.

What he can’t do is unilaterally order the legislative branch to loosen the Treasury’s coffers for $6.6 billion. Nor can he command pharmaceutical companies to pay for $200 vouchers sent to 33 million Medicare beneficiaries for prescription drugs before the election.

Pal­la­dio bags $20 mil­lion Se­ries B to top­ple a prob­lem­at­ic kid­ney dis­ease drug

Palladio Biosciences just took one step further in its quest to topple Otsuka’s Samsca with its own — it hopes safer — autosomal dominant polycystic kidney disease (ADPKD) drug.

The Pennsylvania-based biotech announced a $20 million Series B on Friday, which will fund a 10-person Phase III trial of its vasopressin V2 receptor agonist, lixivaptan. CEO Alex Martin expects to read out data in the first half of next year, then launch straight into a larger pivotal Phase III study with about 1,200 participants.

New York governor Andrew Cuomo (AP Images)

An­drew Cuo­mo says New York will un­der­take its own vac­cine re­view process, and wouldn’t rec­om­mend trust­ing the fed­er­al gov­ern­ment

The concerns keep mounting over President Donald Trump’s politicization of the FDA and other federal agencies guiding the development of a safe and effective vaccine. And today, the telegenic New York governor Andrew Cuomo appeared to introduce even more politics into the matter — latest in an ongoing series of incidents that have cast the proudly independent FDA in starkly political terms.

During his daily press conference Cuomo said that the state will review any coronavirus vaccines approved by the federal government, citing a lack of trust in the Trump administration. The announcement comes one day after Trump accused the FDA of making an “extremely political” move in proposing stricter vaccine guidance.

PhII Alzheimer's fail­ure deals new blow to Roche, AC Im­mune — but the tau hy­poth­e­sis is far from dead

The leading anti-tau antibody has failed its first Phase II testing, casting a shadow on a popular target (just trailing amyloid beta) for Alzheimer’s disease.

Roche and AC Immune are quick to acknowledge disappointment in the topline readout, which suggested that semorinemab did not reduce cognitive decline among patients with early Alzheimer’s disease, who are either just starting to have symptoms or have mild manifestations.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 90,500+ biopharma pros reading Endpoints daily — and it's free.