AstraZeneca’s Setback, Novartis Under Pressure & Scholar Rock’s Approval

AstraZeneca is launching a new breast-cancer drug. But the trial intended to support using it from the start of treatment failed to meet its main goal. At Novartis, pipeline setbacks and shareholder demands put acquisition choices under closer scrutiny.

And Scholar Rock's approval adds a muscle-directed treatment in spinal muscular atrophy. For patients already receiving therapy, the choice now includes extra motor benefit, fracture risk and another regular infusion.

Welcome to The Pharma Closeout Week in Review for Sunday, September thirteenth. I'm Alex Mercer.

And I’m Maya Patel. Here is what happened this week, what changed, and what comes next.

Our top story of the week. On September fourth, AstraZeneca received accelerated U.S. approval for Etcamah, or camizestrant, its oral breast-cancer drug. That allows a mutation-triggered switch during first-line care, before disease progression.

It's for adults with hormone receptor-positive, HER2-negative advanced breast cancer, after at least six months on an aromatase inhibitor plus a CDK4/6 inhibitor. Blood testing every three months looks for an ESR1 mutation. If one appears before progression, the new drug replaces the endocrine treatment while the same CDK4/6 inhibitor continues. That approval came from SERENA-6 and still requires verification of clinical benefit.

Then this Friday, the separate SERENA-4 trial missed its primary progression-free-survival endpoint. It tested starting the drug with the initial advanced-disease regimen. The approval stands, but the opportunity to start treatment with it is a different commercial proposition. How much broader was that study?

It enrolled patients with ER-positive, HER2-negative advanced disease who hadn't received systemic treatment for that advanced cancer. They didn't need an ESR1 mutation to enter. The comparison was camizestrant against anastrozole, each with palbociclib. AstraZeneca reported a numerical improvement but hasn't disclosed its size, so we can't tell how far the trial fell short.

Success would have supported use from the start, without waiting for that mutation. That's the larger opportunity AstraZeneca hasn't secured. For the approved launch, the work is getting eligible patients from a blood-test result to a treatment switch. Where does that leave the other oral options?

They come later. Stemline's Orserdu and Lilly's Inluriyo are approved after progression on at least one endocrine-therapy line. Their setting is ER-positive, HER2-negative, ESR1-mutated advanced breast cancer. Etcamah's switch comes earlier, within first-line treatment, so those approvals don't describe the same treatment decision.

For AstraZeneca, there's still a launch to execute, alongside endocrine treatments such as Faslodex. The setback is to how broadly this new drug can expand.

On the deal side, Frazier Life Sciences closed more than $1.1 billion in commitments to its Public Fund. That brings the vehicle to roughly $2.8 billion raised since 2021. Frazier manages the fund, which focuses on small- and mid-cap public biotech. There's more specialist capital available to invest; where and when it goes to work hasn't been disclosed.

Another financing from earlier in the week: Solstice Oncology launched with a $225 million Series A. Backed by RA Capital, Canaan and Forbion, it plans to test porustobart, a CTLA-4 antibody, with pembrolizumab in colon cancer before surgery.

The planned Phase 2 targets stage two and three microsatellite-stable disease. Canaan's bet is that earlier treatment could succeed where immunotherapy has struggled. That remains unproven here; the study must test benefit without compromising surgery.

Turning to Karyopharm: the company missed a $15.8 million principal installment on September tenth and negotiated a conditional standstill with creditors. It has $252.6 million in outstanding principal on loans and notes, though that wasn't all due that day. Those creditors include funds managed by Highbridge and Braidwell.

The debt grew out of financing and refinancing the business. A 2024 secured loan partly repaid earlier royalty-financing obligations, with the remaining proceeds for expenses and corporate needs, including clinical trials. The standstill has an October fifteenth outside date. Maya, what could bring it to an end sooner?

The FDA refusing to accept the selinexor and ruxolitinib filing in myelofibrosis, or Karyopharm withdrawing it. Acceptance still wouldn't mean approval. The agreement also leaves the defaults and payment deadlines in place.

Separately, Karyopharm expects to issue preferred shares September seventeenth to pay a $20 million fee. Those shares would cover the fee, not settle the debt. And the stakes go beyond the myelofibrosis filing. Karyopharm warns it can't continue as a going concern without funding or a strategic transaction to extend its runway beyond October fifteenth.

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On the regulatory and clinical side, the FDA approved Scholar Rock's ISEMBYLD, apitegromab, on Friday for adults and children age two and older already receiving an SMN2-targeted therapy. The agency calls it the first spinal muscular atrophy treatment that directly targets muscle loss.

That gives Scholar Rock a way into care without replacing the therapy patients already take. How much extra motor benefit does it offer, weighed against the added infusions and fracture risk?

In SAPPHIRE, the advantage over placebo was 2.2 points on the Hammersmith motor-function scale at one year, at the recommended dose. That analysis involved nonambulatory children ages two through twelve on background SMN2 therapy. The p-value was nominal. We shouldn't carry that average across everyone on the label.

For families, this is about basic movements, like rolling over in bed or getting into a sitting position. Doing those with less help can matter day to day. But the average score difference doesn't tell us which ability any one child gained.

And the fracture finding matters alongside those movements. In the study, fractures occurred in nine percent at the recommended dose, versus two percent with placebo. Treatment also means an intravenous infusion every four weeks, on top of the SMN2 therapy that continues. That's the benefit-and-burden discussion clinicians and families now face.

Next, Roivant's PHocus study. We covered the result briefly Tuesday; the walking data deserve a closer look. In pulmonary hypertension associated with interstitial lung disease, inhaled mosliciguat met its randomized Phase 2 primary endpoint. Pulmonary vascular resistance fell by a placebo-adjusted 56.3 percent at sixteen weeks.

A change in blood-flow resistance matters more if patients can do more with it. What did the walking test show?

It measures how far patients can walk in six minutes. At sixteen weeks, the treatment group had a 35.2-meter advantage over placebo on that secondary endpoint. That adds evidence on exercise capacity, without establishing fewer hospitalizations or longer survival. The twenty-four-week follow-up was exploratory, with nominal p-values.

Roivant can take both findings into the next stage: improved vascular resistance and better walking distance. It says Phase 3 PHrontier has begun enrolling. Now a larger study has to show whether they hold up.

Now to Novartis, where the HARBOR miss puts part of the Avidity acquisition's growth case in doubt. Del-desiran failed the primary hand-opening-time endpoint in myotonic dystrophy type one. It was one of three late-stage neuromuscular programs in that $12 billion deal, with launches planned before 2030.

There are also setbacks in programs outside the Avidity deal. Novartis told trade reporters it had paused autoimmune studies of rap-cel, its internally developed CAR-T, over safety concerns. Pelacarsen, licensed from Ionis, missed the primary endpoint of its cardiovascular-outcomes trial. These are separate problems. HARBOR doesn't tell us the other acquired therapies will fail; Novartis is still reviewing the full dataset.

But Novartis hasn't lowered its forecast of five to six percent compound annual sales growth from 2025 through 2030. That keeps the pressure on the remaining pipeline. Reuters reported that shareholder Artisan Partners criticized the deal record and wants board changes and an acquisition committee. The Avidity miss brings the buying decisions into this discussion, alongside what went wrong in the trial.

Our next story is Biohaven's partial clinical hold on BHV-7000 in focal epilepsy. In its September tenth filing, the company described the FDA's September fourth letter. The agency sought more nonclinical data on a metabolite seen in rodents, citing insufficient information to assess human risk. New enrollment is paused; already-randomized patients can continue dosing.

That leaves the two studies in different positions. Biohaven reports no timeline impact for the fully enrolled study, while the other loses enrollment time. We're working from the company's description of the FDA letter, so that reassurance about timing is also Biohaven's assessment.

Continued dosing doesn't resolve the metabolite question. The additional nonclinical work is what Biohaven needs to address before enrollment can resume.

One more regulatory update, from Exelixis. The FDA's decision on zanzalintinib with atezolizumab in previously treated metastatic colorectal cancer is now due March third, 2027. Updated safety and efficacy data were deemed a major amendment. The potential launch moves further out; the extension doesn't tell us whether approval will follow.

In our under-the-radar story this week, we’re returning to Encoded Therapeutics. We covered its financing in our Wednesday episode. This time, we’re looking at the patient results behind the program.

Encoded is developing ETX101, an investigational gene therapy for Dravet syndrome, a childhood epilepsy involving seizures and developmental difficulties. The POLARIS results come from small, open-label Phase 1/2 cohorts. What are we seeing in those children?

These results cover follow-up through fifty-two weeks or the latest visit. In a dose group of five children, the median reduction in monthly countable seizures was about 75 percent. At the next dose level, a group of nine children had a median reduction of about 60 percent. These are sponsor-reported observations, with different follow-up lengths.

That gives the next studies a seizure-control signal to test. The harder question is whether treatment can also change how children develop.

For children treated before age two, Encoded reported cognitive gains against the ENVISION natural-history comparison, with follow-up out to seventy-six weeks. It separately reported adaptive-behavior gains through fifty-two weeks. These observations don't establish a developmental benefit; they weren't randomized evidence. Seizure control and development still need separate proof.

The company's $275 million Series F is intended to advance pivotal and expansion studies and scale up manufacturing. That financing gives Encoded a way to test those questions beyond small cohorts.

The week ahead brings two BioNTech presentations at the World Conference on Lung Cancer. First, updated survival data for gotistobart, a CTLA-4-targeting candidate, are scheduled for early Monday morning, Eastern time.

That's a chemotherapy-free approach in previously treated squamous non-small cell lung cancer after prior PD-L1 therapy. These are stage-one data from the PRESERVE-003 Phase 3 program. The pivotal second stage is still ongoing, so we're looking for longer survival follow-up from that earlier stage.

The second BioNTech presentation comes late Monday night Eastern, crossing into Tuesday. It brings the first global data for a combination using pumitamig, the company's PD-L1-and-VEGF bispecific. It's paired with elfetabart drozuntecan, an antibody-drug conjugate targeting B7-H3.

That Phase 1/2 study includes advanced non-small cell and small cell lung cancer. We'll get an initial activity-and-toxicity picture for that pairing, alongside the longer survival follow-up for the separate approach. Both presentations remain ahead of us.

That’s your Pharma Closeout for this Sunday. Next week, we’ll look at the BioNTech lung-cancer data we previewed and bring you meaningful updates on stories we’ve covered, as they develop.

Enjoy the rest of your Sunday, and thanks for spending part of it with us.

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