Novartis’ $12B Avidity Bet Missed in Phase 3 as Amgen Fell 10.1% on Lp(a) Readacross and the FDA Approved AstraZeneca’s Etcamah on a ctDNA Resistance Signal (September 9, 2026)

Last updated: September 9, 2026

Novartis’ del-desiran missed its Phase 3 primary endpoint in myotonic dystrophy, the third pipeline blow in a week. Amgen fell 10.1% on Lp(a) readacross despite an overall survival win for Imdelltra, and the FDA approved AstraZeneca’s Etcamah on a ctDNA signal.

This page covers the September 8, 2026 news cycle: the HARBOR trial failure and what it means for the $12 billion Avidity acquisition, the Amgen selloff and the DeLLphi-305 result it overshadowed, the Etcamah approval and its regulatory history, Boston Scientific’s guidance withdrawal, and the day’s financings and market closes.

What happened to Novartis’ del-desiran in the HARBOR trial?

Del-desiran (delpacibart etedesiran) did not meet the primary endpoint of the Phase 3 HARBOR study in myotonic dystrophy type 1, failing to show a statistically significant improvement over placebo on video hand opening time. Novartis disclosed no p value and no effect size in its September 8 release.

HARBOR enrolled roughly 150 people with myotonic dystrophy type 1 (DM1), a genetic neuromuscular disease with no approved disease modifying treatment. The primary endpoint, video hand opening time (vHOT), measures how quickly the hand relaxes after a squeeze, the myotonia that defines the disease. Secondary endpoints included hand grip strength, quantitative muscle testing, the DM1-Activ measure of daily living, and the 10 meter walk run test. Novartis said “evidence of clinical activity in secondary endpoints and exploratory analyses were observed” but published none of those figures, saying it will evaluate the full dataset and engage health authorities on a path forward. Chief medical officer Shreeram Aradhye called setbacks “part of scientific progress.”

That language matters less than what was not in the release. For the third time in five days, a Novartis outcome disclosure arrived with the numbers withheld: pelacarsen’s Lp(a)HORIZON miss on September 4 carried no hazard ratio, and the del-desiran release carries no vHOT delta. Both datasets are now debts due at future congresses.

What does the miss change about the $12 billion Avidity deal?

Del-desiran was the most advanced asset in Avidity Biosciences’ antibody oligonucleotide conjugate platform, the centerpiece of the $12 billion acquisition Novartis struck in 2025. The lead program’s first Phase 3 readout under Novartis ownership is now a miss with no disclosed magnitude.

Before the readout, Barclays analysts had projected peak annual sales of about $3.1 billion for del-desiran and assigned it a 60% probability of success on the strength of Phase 2 data, per Reuters and Yahoo Finance reporting. The platform thesis is not dead: Avidity’s pipeline includes programs in facioscapulohumeral muscular dystrophy and Duchenne, and Novartis says it is evaluating the full HARBOR dataset. But the deal was priced for a lead asset that worked, and the market repriced accordingly. American depositary receipts of Novartis closed at $137.70 on September 8, down 13.9% from the prior US session. The move compressed two Zurich trading days into one American session, since US markets were closed Monday for Labor Day; the Zurich listed shares fell roughly 9% on Tuesday alone, a decline CNBC reported was tracking toward the stock’s worst single day on record, with Reuters putting the erased market value near 24 billion Swiss francs, about $29.6 billion. Coverage widely framed it as the third setback in a week, counting the September 2 pause of the rap-cel autoimmune cell therapy trials and the September 4 pelacarsen failure alongside HARBOR.

Why did Amgen fall 10.1% on the day it announced a survival win?

Amgen closed down 10.1% at $393.17 on September 8, and none of the decline traces to new Amgen data. Press coverage attributed the selloff to readacross from pelacarsen’s failure to Amgen’s Lp(a) program olpasiran, compounded by a BMO Capital downgrade.

Olpasiran is a small interfering RNA that lowers lipoprotein(a) by more than 90% in earlier studies, and its Phase 3 OCEAN(a) Outcomes trial (NCT05581303) is ongoing with no readout. Pelacarsen is a different modality, an antisense oligonucleotide, but the two programs share the same wager: that lowering Lp(a) prevents cardiovascular events. Lp(a)HORIZON printed a null on that wager in the overall population, and until the pelacarsen data are presented, nobody outside Novartis knows whether the miss was a near thing or a zero. Seeking Alpha reported the slide as olpasiran read through concern; Yahoo Finance noted BMO Capital cut Amgen from Outperform to Market Perform the same morning while keeping a $450 target, citing the stock’s roughly 34% year to date run and coming losses of exclusivity. Amgen made no public statement about olpasiran on Tuesday within the scope of our sweep.

The paradox is that September 8 also brought Amgen’s best oncology news of the year, and the market did not pay for it.

What did Amgen’s DeLLphi-305 trial show?

Imdelltra (tarlatamab-dlle) plus durvalumab significantly extended overall survival versus durvalumab alone as first line maintenance in extensive stage small cell lung cancer, meeting the Phase 3 DeLLphi-305 primary endpoint at a planned interim analysis. Amgen disclosed no hazard ratio and no median survival figures.

The trial randomized 563 patients who had not progressed after initial treatment with durvalumab, platinum chemotherapy and etoposide, adding the DLL3 targeted T cell engager to maintenance in one arm. Amgen said secondary endpoints of progression free survival and objective response rate were also met, that safety was consistent with the known profiles of both drugs, and that detailed data will go to an upcoming medical congress it did not name. R&D chief Jay Bradner called the results “landmark” and said they position Imdelltra to move into the first line setting, where small cell lung cancer still kills most patients within two years of diagnosis.

Note the structure: this is a withheld number after a win, which costs the holder nothing and gives them a second catalyst at the congress. Del-desiran’s is a withheld number after a miss, a debt the sponsor must eventually pay at a venue it does not control. The two releases landed hours apart and the market priced only one of them into Amgen’s stock, and it was not this one.

What did the FDA approve for AstraZeneca, and why is it a first?

The FDA granted accelerated approval to Etcamah (camizestrant), AstraZeneca’s oral selective estrogen receptor degrader, for HR positive, HER2 negative advanced breast cancer upon detection of an ESR1 mutation during aromatase inhibitor and CDK4/6 inhibitor therapy. It is the first cancer approval triggered by a resistance mutation found in blood before imaging shows progression.

The approval, announced Friday September 4 and absorbed by the market after the holiday weekend, rests on the SERENA-6 trial, which used circulating tumor DNA monitoring to catch emergent ESR1 mutations in first line patients and switched them to camizestrant before radiographic progression. The FDA simultaneously authorized Guardant Health’s Guardant360 CDx as the companion diagnostic. Angelo de Claro of the FDA’s Oncology Center of Excellence called it “the first FDA approval of a cancer therapy guided by the detection of a resistance mutation in circulating tumor DNA (ctDNA) before imaging tests show that the disease is progressing.” AstraZeneca estimates about 30% of patients with endocrine sensitive disease develop ESR1 mutations during first line treatment, within a US first line population of roughly 37,000. The label carries a boxed warning for cardiac rhythm risk with certain concomitant medications.

What did the SERENA-6 data show?

Switching to camizestrant at ESR1 mutation detection cut the risk of progression or death by 56% versus continuing standard therapy. Median progression free survival was 16.0 months against 9.2 months. Overall survival data remain immature.

Source: AstraZeneca US press release, September 4, 2026.

How did Etcamah overcome a negative advisory committee vote?

The Oncologic Drugs Advisory Committee convened on April 30, 2026 and voted against camizestrant, with BioSpace and CancerNetwork reporting the count as 6 to 3. Four months later the agency approved the drug anyway, the third time in under two months the FDA has overridden a contested review posture.

Panelists questioned whether SERENA-6 answered the clinical question that matters: whether switching at ESR1 mutation emergence beats waiting for radiographic progression, since every patient eventually gets a next line therapy. Leerink analysts wrote after the approval that clinicians share the doubt, and pegged the approved indication at modest revenues of roughly $750 million, rising toward $2.9 billion only if the first line SERENA-4 trial reads out positive in the second half of 2026. The pattern for regulatory handicappers now has three 2026 exhibits: Replimune’s Tudriqev was approved after two rejections and hostile briefing documents, uniQure’s AMT-130 reached its Huntington’s BLA filing after the agency reversed its earlier resistance to the program, and camizestrant cleared a 6 to 3 no vote. Adverse committee optics keep proving to be variance, not verdicts.

What did Boston Scientific’s 8-K say about the cyberattack?

Boston Scientific told the SEC on September 8 it is “unlikely to meet the net sales growth and adjusted EPS guidance ranges for the third quarter and full year 2026” and that the August cyberattack will have a material impact on results in both periods. It attached no numbers; revised guidance comes October 28.

The Item 1.05 filing is the disclosure we have been watching for since the incident surfaced in late August, and it arrived half full. Operationally, the company reports its distribution network substantially restored with major centers processing orders at or above normal levels, all sterilization facilities operational, and manufacturing resumed across most facilities globally, though it calls the timeline for full recovery uncertain. Financially, it says only that guidance issued July 29 is out of reach, that some portion of impacted revenue should be recovered as backlogs clear, and that management does not expect material long term damage. J.P. Morgan analysts noted, per MedTech Dive, that Boston Scientific’s disposables heavy mix gives it less room to recapture lost sales than Stryker had after its March attack, with four months left in the fiscal year against Stryker’s nine to ten. Shares closed at $44.98, down 5.9% from the prior session. Separately, MedTech Dive reported NovoCure disclosed that a mid August breach exposed more than 1,400 patient records, the sector’s second active cyber incident.

Which numbers were withheld this week, and when do they come due?

Four major readouts have now been announced without their headline figures in five days. Three follow misses and one follows a win, and the distinction determines who owes whom.

What else moved on September 8?

Two private financings and two clinical wins rounded out the day. BrainChild Bio closed a $116 million Series A to push CAR T cell therapy for pediatric brain tumors into a pivotal trial in diffuse intrinsic pontine glioma, evidence that ex vivo cell therapy still finances in oncology while the autoimmune side of the field sits in a safety pause. Moonwalk Biosciences raised a $70 million Series B, with Eli Lilly and ARCH Venture Partners participating, for MW101, a small interfering RNA therapy aimed at adipose tissue in obesity, with first in human trials planned for late 2027. Spyre Therapeutics said its anti IL-23 antibody SPY003 met the induction primary endpoint in the Phase 2 SKYLINE ulcerative colitis trial, completing proof of concept for all three antibodies in its planned inflammatory bowel disease combinations. And Roivant’s Pulmovant presented positive Phase 2 PHocus results for mosliciguat, its inhaled sGC activator licensed from Bayer, in pulmonary hypertension associated with interstitial lung disease at the ERS congress, unveiling an ongoing Phase 3 called PHrontier. In medtech, Abbott won FDA approval for its TactiFlex Duo ablation catheter, which delivers both pulsed field and radiofrequency energy for atrial fibrillation, and Sandoz laid out a biosimilars buildout it says runs through 2040.

How did the market close on September 8?

Official exchange closes for September 8 versus the September 4 session (US markets were closed Monday September 7 for Labor Day). Market data; no cause assigned unless a company disclosure exists.

Frequently asked questions

What is del-desiran?

Del-desiran (delpacibart etedesiran) is an antibody oligonucleotide conjugate developed by Avidity Biosciences, now Novartis, that delivers an siRNA into muscle cells to reduce the toxic DMPK RNA that causes myotonic dystrophy type 1.

Did the HARBOR trial disclose any numbers?

No. Novartis said the primary endpoint of video hand opening time was not met and reported no p value, no effect size, and no secondary endpoint figures. It said full data will be evaluated and discussed with health authorities.

Is myotonic dystrophy type 1 treatable today?

No disease modifying treatment is approved anywhere for DM1. Management is symptomatic. That unmet need is why HARBOR’s failure lands hard on patients as well as on Novartis’ deal math.

Why did Amgen stock drop if its lung cancer trial succeeded?

Press coverage attributed the 10.1% decline to readacross from pelacarsen’s Lp(a) outcomes failure to Amgen’s olpasiran, plus a BMO Capital downgrade on valuation. The DeLLphi-305 survival win, announced the same day without figures, did not offset the selloff.

What is olpasiran?

Olpasiran is Amgen’s small interfering RNA that lowers lipoprotein(a). Its Phase 3 OCEAN(a) Outcomes trial is ongoing, and no cardiovascular outcomes data for the drug exist yet.

Does the pelacarsen failure prove olpasiran will fail?

No. It removes the assumption that Lp(a) lowering translates to fewer events, which was the basis for the class trade. Whether magnitude, duration, or modality can rescue the hypothesis is exactly what OCEAN(a) will test.

What is Imdelltra and how does DeLLphi-305 change its use?

Imdelltra (tarlatamab-dlle) is a DLL3 targeted T cell engager approved in previously treated small cell lung cancer. DeLLphi-305 showed adding it to durvalumab maintenance extends survival in the first line setting, which would move it far earlier in treatment if approved there.

What exactly did the FDA approve Etcamah for?

For adults with HR positive, HER2 negative advanced breast cancer whose tumors develop an ESR1 mutation, detected by an FDA authorized test, while on an aromatase inhibitor plus a CDK4/6 inhibitor. Patients switch the endocrine backbone to camizestrant while continuing the CDK4/6 inhibitor.

Why is the Etcamah approval historic?

It is the first FDA cancer approval that acts on a resistance mutation found in blood before scans show progression, per the FDA’s own oncology leadership. It effectively makes serial ctDNA monitoring an actionable part of the treatment paradigm.

Did the FDA’s advisory committee support camizestrant?

No. The Oncologic Drugs Advisory Committee, convened April 30, 2026, voted against it, with the count reported by BioSpace and CancerNetwork as 6 to 3. The FDA approved the drug regardless, using the accelerated approval pathway.

What did Boston Scientific actually say about its 2026 guidance?

In an 8-K filed September 8, it said it is unlikely to meet the third quarter and full year 2026 net sales growth and adjusted EPS guidance issued July 29, that the cyberattack’s impact will be material, and that revised guidance will come with third quarter results on October 28.

Is Boston Scientific’s business back online?

Largely. The company says distribution is substantially restored, sterilization facilities are operational, and manufacturing has resumed across most facilities, but it has not put a date on full recovery and has not quantified the financial damage.

Who funded BrainChild Bio and Moonwalk Biosciences?

BrainChild Bio closed a $116 million Series A for pediatric brain tumor CAR T therapy. Moonwalk Biosciences raised a $70 million Series B led by Alpha Wave Ventures and YK Bioventures, with Eli Lilly, ARCH Venture Partners, Khosla Ventures, Gaorong Ventures and Future Ventures participating.

When will the missing trial numbers be published?

Novartis has committed pelacarsen and del-desiran data to future congresses without naming them. Amgen says DeLLphi-305 data will go to an upcoming congress. No Novo Nordisk primary document on the ziltivekimab discontinuations exists as of September 8.

Sources

Primary sources: Novartis press release on the HARBOR Phase III study (September 8, 2026); Amgen press release on DeLLphi-305 (September 8, 2026, via PR Newswire); AstraZeneca US press release on Etcamah approval (September 4, 2026); FDA press announcement on the Etcamah accelerated approval (September 4, 2026); Boston Scientific Form 8-K, Item 1.05 (filed September 8, 2026); BrainChild Bio Series A release (GlobeNewswire, September 8, 2026); Spyre Therapeutics SKYLINE release (GlobeNewswire, September 8, 2026); Roivant/Pulmovant PHocus release (GlobeNewswire, September 8, 2026); Abbott TactiFlex Duo release (PR Newswire, September 2026). Market data: official exchange closes, September 4 and September 8, 2026.

Trade press and analyst commentary (attributed): Reuters and Yahoo Finance on the Novartis market reaction and Barclays estimates (September 8, 2026); CNBC on the Novartis share decline (September 8, 2026); Seeking Alpha and Yahoo Finance on the Amgen selloff and BMO Capital downgrade (September 8, 2026); BioSpace and CancerNetwork on the April 30 ODAC vote; Leerink analyst commentary via BioSpace (September 8, 2026); MedTech Dive on Boston Scientific and NovoCure (September 8, 2026); Fierce Biotech and Fierce Pharma coverage (September 8, 2026).

Related coverage

• Pelacarsen’s Lp(a)HORIZON failure and the ziltivekimab discontinuations, with the surrogate framework this week’s tape is trading on
• Ivonescimab’s overall survival win and the Ultragenyx Angelman failure
• The Novartis and BMS autoimmune CAR T pauses that opened the cell therapy safety story
• Our first coverage of the Boston Scientific cyberattack
• The binary ledger reference table