Kate Haviland, Blueprint Medicines CEO

Blue­print met all its end­points in bid for ex­pand­ed Ay­vak­it la­bel — but stock trends low­er any­way

Blue­print Med­i­cines an­nounced this morn­ing that the sec­ond part of its study on Ay­vak­it in non-ad­vanced sys­temic mas­to­cy­to­sis (SM) — a rare dis­ease in which a type of white blood cells known as mast cells builds up — met all end­points, but the bio­phar­ma left key ques­tions unan­swered.

In 212 pa­tients, with 141 in the treat­ment arm and 71 in the con­trol arm, pa­tients who got Ay­vak­it saw an av­er­age 15.6-point de­crease in their symp­tom scores com­pared to a 9.2-point de­crease in the place­bo arm at 24 weeks. In an ex­ten­sion study, those on Ay­vak­it saw their symp­tom scores drop by 20.2 points by week 48.

Lat­er this year, the Mass­a­chu­setts biotech plans to file for a sup­ple­men­tary ap­proval for Ay­vak­it, which was green­lit for the rar­er ad­vanced form of SM back in 2021.

De­spite the ap­par­ent pos­i­tive read­out, Blue­print $BPMC was trad­ing down by over 20% this morn­ing, drop­ping from around $68 to $54.

For one, an­a­lysts not­ed that the dif­fer­ence be­tween the av­er­age symp­tom scores of the treat­ment and place­bo arms in the Part 2 re­sults was just over 6 points, sub­stan­tial­ly less than the 16-point dif­fer­ence in the small­er Part 1 study. Not on­ly did the treat­ment have a small­er ef­fect in Part 2 than in Part 1, in which pa­tients saw a 19-point im­prove­ment in their symp­tom scores, but the place­bo plus stan­dard of care fared con­sid­er­ably bet­ter than in Part 1 as well, where the con­trol arm saw on­ly a 3-point im­prove­ment in symp­tom scores.

Christy Rossi

When asked about the dif­fer­ence in the con­trol arm, Blue­print COO Christy Rossi told End­points News that it was “hard to spec­u­late,” but not­ed the mul­ti-cen­ter, glob­al scale of the sec­ond part of the study.

In ad­di­tion, Blue­print didn’t share ex­act num­bers on a key sec­ondary end­point — re­spon­der rate — leav­ing the ques­tion of how many pa­tients the treat­ment worked for on the ta­ble, though it did reach sta­tis­ti­cal sig­nif­i­cance here. Rossi main­tained that Blue­print would in­clude that da­ta in a fu­ture con­fer­ence pre­sen­ta­tion.

The re­spon­der rate, or the pro­por­tion of pa­tients with a ≥30% de­crease in to­tal symp­tom score, was ini­tial­ly the pri­ma­ry end­point of the study, but fol­low­ing dis­cus­sions with the FDA, Blue­print swapped its pri­ma­ry and sec­ondary end­points for the study.

Phili­na Lee

In ad­di­tion, when asked about price dur­ing the in­vestor call, Blue­print chief com­mer­cial of­fi­cer Phili­na Lee didn’t go in­to specifics, say­ing, “As we get clos­er to a po­ten­tial launch, we will con­tin­ue to en­gage with providers and pay­ers and oth­er stake­hold­ers, and we will use all of these in­puts to in­form our ul­ti­mate pric­ing ap­proach.”

All of these is­sues lead up to one ma­jor ques­tion: Will the ex­pand­ed la­bel in­to non-ad­vanced SM make Blue­print prof­itable?

Ay­vak­it, Blue­print’s long­time lead drug, was first ap­proved for a very spe­cif­ic form of in­testi­nal can­cer in 2020. At the time, the bio­phar­ma priced Ay­vak­it at $32,000 a month, a price point that was twice what an­a­lysts an­tic­i­pat­ed, as well as one it main­tained when Ay­vak­it was ap­proved for ad­vanced SM. Last year, Ay­vak­it made $53 mil­lion, while Blue­print func­tioned at a loss of $644 mil­lion. In the first half of this year, Blue­print has made $52 mil­lion, and ex­pects Ay­vak­it sales rev­enue to jump to $115 to $130 mil­lion for 2022.

While SVB Se­cu­ri­ties an­a­lysts de­scribed the non-ad­vanced SM da­ta as “ap­prov­able,” they not­ed:

In our view, these da­ta will fur­ther mag­ni­fy the com­mer­cial de­bate, as in­vestors ques­tion the size of the ad­dress­able ISM pop­u­la­tion for a chron­i­cal­ly used ther­a­py with a lim­it­ed treat­ment ef­fect that could cost >$350,000 per year. We think some physi­cians, pay­ors and pa­tients may balk at the an­tic­i­pat­ed cost giv­en that Ay­vak­it ap­pears to add about a 10% im­prove­ment in symp­toms ver­sus best sup­port­ive care.

The an­a­lysts al­so added that Blue­print’s da­ta Wednes­day “opens the door for com­pe­ti­tion” from the likes of Co­gent Bio­sciences, “while large­ly de-risk­ing the con­cerns about a large place­bo ef­fect caus­ing the tri­al to fail.” Co­gent has a read­out for its drug bezu­clas­tinib in non-ad­vanced SM slat­ed for ear­ly next year, and its stock $COGT was trad­ing up 18% Wednes­day morn­ing.

The Fac­tors Dri­ving a Rapid Evo­lu­tion of Gene & Cell Ther­a­py and CAR-T Clin­i­cal Re­search in APAC

APAC is the fastest growing region globally for cell & gene therapy trials representing more than a third of all cell & gene studies globally, with China leading in the region. 

APAC is the leading location globally for CAR-T trials with China attracting ~60% of all CAR-T trials globally between 2015-2022. The number of CAR-T trials initiated by Western companies has rapidly increased in recent years (current CAGR of about 60%), with multiple targets being explored including CD19, CD20, CD22, BCMA, CD30, CD123, CD33, CD38, and CD138.

The End­points 11; blue­bird's $3M gene ther­a­py; Bio­gen tout new neu­ro da­ta; Harsh re­views for can­cer drugs; 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.

Reading about John Carroll’s pick of biotech’s most promising startups has become a treasured tradition. If you ever get curious about previous classes of the Endpoints 11, you can find all of them (plus a number of our other regular specials) here.

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EMA warns of short­ages of two Boehringer heart drugs due to a spike in de­mand

The EMA is putting EU member states on alert over the shortage of two drugs that counter heart attacks due to an uptick in demand.

On Friday, the EMA sent out a warning that two Boehringer Ingelheim drugs are experiencing a shortage: Actilyse and Metalyse. The drugs are used as emergency treatments for adults experiencing acute myocardial infarction, or a heart attack, by dissolving blood clots that have formed in the blood vessels.

The End­points 11: The top pri­vate biotechs in pur­suit of new drugs. Push­ing the en­ve­lope with pow­er­ful new tech­nolo­gies

Right around the beginning of the year, we got a close-up look at what happens after a boom ripples through biotech. The crash of life sciences stocks in Q1 was heard around the world.

In the months since, we’ve seen the natural Darwinian down cycle take effect. Reverse mergers made a comeback, with more burned out shells to go public at a time IPOs and road shows are out of favor. And no doubt some of the more recent arrivals on the investing side of the business are finding greener pastures.

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Mene Pangalos (AstraZeneca via YouTube)

As­traZeneca shuts the PhI­II door for Ion­is' PC­SK9 drug de­spite pos­i­tive PhI­Ib

When Ionis and AstraZeneca unveiled the first round of mid-stage data for their antisense PCSK9 drug, Mene Pangalos, AstraZeneca’s EVP of biopharmaceuticals R&D, underscored the drug’s “potential best-in-class efficacy profile.”

But now that the second batch is in, it appears AZD8233 isn’t hitting the mark after all.

Ionis announced Friday morning that although the candidate, also dubbed ION449, met the primary endpoint in the Phase IIb SOLANO trial, its partners at AstraZeneca have decided not to move it into Phase III studies because the “results did not achieve pre-specified efficacy criteria.”

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Up­dat­ed: Bio­gen throws it­self back in­to mud­dled da­ta ar­gu­ments with more de­tails on its an­ti­sense ALS drug

With a highly watched FDA decision deadline coming in late January, Biogen and Ionis dropped the full data on the Phase III study of their ALS drug tofersen in the New England Journal of Medicine on Wednesday.

Biogen is looking for approval for tofersen in a very small subset of ALS patients — some 2%, according to the paper — who have a SOD1 gene mutation, which has previously been linked to ALS. Tofersen is meant to reduce levels of mutant SOD1 proteins.

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As­traZeneca, Mer­ck cull one Lyn­parza in­di­ca­tion in heav­i­ly pre­treat­ed ovar­i­an can­cer pa­tients

Just one day after blockbuster Lynparza got access to another indication in China, its Big Pharma owners have decided to withdraw it in certain patients after reviewing Phase III data.

The two companies that work together on Lynparza decided to recall one of the indications several weeks ago in a specific type of ovarian cancer, Lynparza’s first indication when it was first FDA-approved in 2014. Initial data showed that rates of overall survival in patients with at least three rounds of chemo before getting on the PARP inhibitor were lower than in patients with less previous chemo treatment.

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Solicitor General Elizabeth Prelogar

Should SCO­TUS hear Am­gen's Repatha case? So­lic­i­tor gen­er­al says no

Back in April, Amgen said it was encouraged by the solicitor general’s anticipated review of its Supreme Court petition to rehear a Repatha patent case. They’re likely much less optimistic about the outcome now.

Solicitor General Elizabeth Prelogar wrote in a recent 27-page brief that Amgen’s arguments “lack merit and further review is not warranted.”

The case traces back to a suit filed in 2014 against Sanofi and Regeneron’s Praluent, which ended up beating Amgen’s PCSK9 blockbuster Repatha to market by a month just a year later.

Phil Sharp, Nobel Prize laureate (L), and John Carroll, Endpoints News co-CEO (via Michael Last)

The End­points 11: Fire­side chat with No­bel Prize lau­re­ate Phil Sharp

On Thursday evening in Boston I had the great good fortune to talk about the creation of the biotech industry with Nobel Prize-winning scientist Phil Sharp. I learned quite a bit about the early days of Genentech, Biogen and Alnylam, which all helped birth this unusual drug development ecosystem. And that’s why we can do things like the Endpoints 11. Here’s my talk with Phil Sharp, which you can either watch or read below.

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