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.

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.

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.

Pre-pandemic, the life sciences industry had settled into a pattern. The average drug took 12 years and $2.9 billion to bring to market, and it was an acceptable mode of operations, according to Nimita Limaye, Research Vice President for Life Sciences R&D Strategy and Technology at IDC.

COVID-19 changed that, and served as a proof-of-concept for how technology can truly help life sciences companies succeed and grow, Limaye said. She recently spoke about industry trends at Egnyte’s Life Sciences Summit 2022. You should watch the entire session, free and on-demand, but here’s a brief recap of why she’s urging life sciences companies to embrace digital transformation.

James Sabry’s BD team at Roche has a long track record in hunting the globe for new biotech deals. But they’ve never journeyed into China before to ink a worldwide development and commercialization pact with a China-based biotech on an experimental med.

As Max Gelman reported yesterday, Roche fronted a new alliance with China’s Jemincare with $60 million in cash and $590 million in milestones for worldwide commercial rights to an oral androgen receptor degrader. The deal itself is fairly typical of an early-stage alliance around a promising treatment. The Shanghai-based biotech is largely unknown outside China, but this is a classic high-risk, modest upfront pact that Roche routinely inks.

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Martin Landray knows what controversy in clinical drug development feels like, from first-hand experience.

Landray was the chief architect of RECOVERY, a study that pitted a variety of drugs against Covid-19. And he offered some landmark data that would help push dexamethasone out into broader use as a cheap treatment, while helping ice hydroxy’s reputation as a clear misfire.

“Lots of people told us we shouldn’t use it,” Landray says about dexamethasone and Covid-19. “It was dangerous. We shouldn’t even do a trial. They also cared about hydroxychloroquine and lots of people said we shouldn’t do a trial because it must be used. I’ve got the letters from both sets of people.”

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Biopharma companies that win new accelerated approvals typically have no financial incentive to complete their confirmatory trial because the price of the treatment doesn’t change once an accelerated approval converts to a full approval, researchers from Harvard, the University of Pennsylvania and the Brookings Institution wrote in a new Health Affairs study published yesterday.

Even as new cancer drugs approved under the AA pathway are launched at prices in excess of $100,000, companies often gain little from completing a quick confirmatory trial, and at least part of the problem, the researchers say, is that the FDA rarely withdraws a drug from the market because a company has failed to conduct a confirmatory trial or because the confirmatory trial showed no benefit.

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PI3K is a protein that is part of a pathway that regulates cell growth, survival and metabolism — earning it the inscription of master regulator for cancer. However, while a number of PI3K inhibitor drugs have been approved since 2014, the class as a whole has dwindled, as it has been plagued by toxicity issues in various blood cancers.

For example, the FDA hit Secura Bio’s PI3K inhibitor Copiktra, which earned accelerated approval in 2018, with an increased death warning in June following the results of its confirmatory Phase III trial. That warning came after a number of companies, including Secura, Gilead and Incyte, withdrew their accelerated approvals for their PI3K inhibitors after failing to complete confirmatory trials. The FDA now requires randomized trials to be conducted for PI3K inhibitors in blood cancers.

Roche’s Genentech is going high style next month for New York Fashion Week. The pharma is hosting its first-ever runway fashion show to raise disability visibility, featuring models from the spinal muscular atrophy (SMA) community.

“Double Take” will be held Sept. 8, the day before the official New York event begins, with models walking and rolling across the stage wearing stylish and functional adaptive clothing. Eleven people living with SMA and four advocates will show off the custom fashions created by Open Style Lab, a Brooklyn nonprofit and accessible clothing design collaborative.

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As Congress continues to mull whether and how to reform the FDA’s accelerated approval pathway, new research on the pathway continues to crop up, attempting to guide the way for new reforms.

Earlier this week, several prominent researchers from Harvard, UPenn and the Brookings Institution called for new financial incentives to encourage companies to finish the trials necessary to convert accelerated approvals to full approvals, or at least reform how companies are paid after winning an accelerated approval.

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It’s been just two days since Endo International filed for bankruptcy in an attempt to dig itself out of thousands of opioid lawsuits. Now one of its top sellers is in trouble.

A federal appeals court on Thursday affirmed a Delaware judge’s decision that Eagle Pharmaceuticals’ generic version of Endo’s vasopressin injection Vasostrict does not infringe on the company’s patents. Eagle’s version won approval back in December, and already, the generic and others like it have driven down Vasostrict sales.

Another Covid-19 vaccine will enter the fray as the EMA kicks off its conditional marketing authorization application for SK’s vaccine, dubbed Skycovion.

SK Chemicals GmbH submitted data to the EMA on how well the vaccine triggers the production of antibodies against the original strain of SARS-CoV-2, along with data on the safety and quality of the vaccine.

“The evaluation of Skycovion is one of the ongoing evaluations of data on Covid-19 vaccines. As the pandemic continues to evolve, it is important that the EU has a wide array of vaccines and treatments to enable the Member States to combat the pandemic effectively. EMA and its scientific committees are committed to ensuring a robust review of all data on COVID-19 vaccines and medicines,” the EMA said in a statement.

Bioscience & Technology Business Center The University of Kansas Lawrence, Kansas

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