Merck's reported $11B Acceleron buy could help it diversify; antitrust hurdles loom

 Merck has emerged as a finalist to acquire Acceleron for around $11 billion. The deal dovetails with the Big Pharma company’s plan to diversify beyond its immuno-oncology megablockbuster Keytruda, but overlapping businesses could attract antitrust scrutiny, two analysts say.

Merck is in advanced talks to buy Acceleron in what could be one of the New Jersey drugmaker’s biggest deals, The Wall Street Journal reported Monday, citing people familiar with the matter. The price tag would land around $180 per share for a total of over $11 billion, Bloomberg reported Friday.

If successful, the deal would give Merck the FDA-approved anemia drug Reblozyl, which Acceleron markets with partner Bristol Myers Squibb. But the real focus is sotatercept, an experimental drug for pulmonary arterial hypertension (PAH), and that med could spell trouble for the deal with regulators, SVB Leerink analysts Daina Graybosch, Ph.D., and Geoffrey Porges said in separate notes Tuesday.

Merck entered the PAH space in 2014 through a licensing deal with Bayer on first-in-class sGC modulator Adempas. And Merck recently pushed an inhaled sGC agent, MK-5475, into a phase 2/3 trial in PAH.

Sotatercept does have a different mechanism of action: It is designed to restore BMPR-II signaling, a driver of PAH. While keeping both sotatercept and MK-5475 would strengthen Merck’s PAH presence, doing so would likely “cause regulatory scrutiny and slow deal close,” Graybosch said in her note. The U.S. Federal Trade Commission might require Merck to divest MK-5475, Porges wrote in his note. Another explanation? It's possible “that program has run into obstacles promoting this overture,” he added.

Acceleron’s PAH candidate could reach over $2 billion in peak sales by Porges’ estimate, constituting about two-thirds of Acceleron’s current value, he said. Assuming sotatercept is successful, Porges put Acceleron’s share price at $182, which makes the reported deal price a fair offer, he figured.

Merck has long been under investor pressure to reduce its reliance on Keytruda, even as the PD-1 inhibitor expands its lead across a range of cancer types. About half of Merck’s 2026 sales will come from Keytruda, and the addition of Acceleron would reduce that percentage to 48% if sotatercept successfully launches by 2024, Graybosch predicts.

Beyond the obvious injection of additional revenues, “Merck could realize significant cost synergies with the transaction, as it absorbs the program teams and cuts overhead,” Graybosch said.

What’s more, Merck is moving from a strengthened balance sheet after its $9 billion spinoff of Organon, Porges noted. As of the second quarter, the New Jersey pharma had $8.6 billion in cash and a relatively low debt-to-EBITDA ratio of 1.4x.

Merck may look like a reasonable new home for Acceleron, but other companies with interests in cardiovascular disease and enough cash could throw their hats in the ring, Porges suggested.

BMS would be a natural bidder, and the best fit in Porges’ view, given its existing 11.5% stake in Acceleron, which it got from the Celgene acquisition. BMS CEO Giovanni Caforio, M.D., has confirmed the company’s intention to secure its growth path for the second half of the decade by seeking out deals.

Cardiovascular disease is also a core focus area at BMS, as evident in its recent $13.1 billion acquisition for Myokardia, developer of obstructive hypertrophic cardiomyopathy candidate mavacamten. Sotatercept could “contribute to a cadence of launches in the cardiovascular space” for BMS, Porges said.

Pfizer, which has largely been quiet on the M&A front in recent years, could also be a potential acquirer. Pfizer’s experience in pulmonary hypertension includes Revatio, which is marketed by Viatris, and Viagra, plus a CDK4/6 inhibitor dubbed PF-06842874 in phase 1 development for PAH, Porges noted.

As for PAH bigwig Johnson & Johnson, it's unlikely to make a move, Porges said, despite having plenty of financial firepower to pull off such a deal. J&J claims over 50% of the PAH market thanks to its 2017 acquisition of Actelion. That would make an Acceleron acquisition difficult to get past antitrust regulators.

https://www.fiercepharma.com/pharma/buying-acceleron-for-11b-a-good-fit-for-merck-to-diversify-from-keytruda-but-antitrust

In preclinical tests, Merck’s COVID-19 antiviral seems to work against variants

 Merck & Co. is reporting preclinical work showing that the experimental COVID-19 treatment it is developing with Ridgeback Therapeutics will likely block common variants of the SARS-CoV-2 virus, including the highly transmissible delta variant.

The treatment, an oral antiviral called molnupiravir, is in two Phase 3 human clinical trials, one as a treatment for early COVID-19 disease, the other for prevention of SARS-CoV-2 infection.

The experiments on variants were not performed in humans, but Jay Grobler, Merck’s executive director of infectious diseases and vaccines, says that “molnupiravir is equally active across all the variants we looked at,” and that the variants the firm tested are representative of those circulating the globe. Because of when the experiments were performed, the data do not include the newly described mu variant.

The results were reported during IDWeek, the annual meeting of several infectious disease organizations, including the Infectious Diseases Society of America. If molnupiravir is cleared by the US Food and Drug Administration, it will be only the second approved COVID-19 antiviral. Gilead Sciences’ Velkury (remdesivir) has been in use for much of the 18-month pandemic, but the treatment is an infusion that must be given in the hospital.

Molnupiravir is a nucleoside analog—it looks like the natural building blocks of the virus’s genome, so when the SARS-CoV-2 virus tries to copy itself, the enzyme that stitches that genetic information together is fooled into incorporating the antiviral into the growing chain. The virus can’t easily build itself with that doctored information, and it becomes non-infectious.

“Even if you see the virus, it can’t replicate,” Grobler says. “It’s sort of like a dead-end product.”

The molnupiravir tests were very preliminary: the compound was only examined for its ability to prevent the growth of virus in cells. But Grobler says he is confident the results will be similar in people with COVID-19. To that end, Merck and Ridgeback are collecting virus samples from people in the ongoing Phase 3 trials to determine which variant each person has. Those trials are expected to be completed in the coming months.

https://cen.acs.org/pharmaceuticals/drug-development/preclinical-tests-Mercks-COVID-19/99/i36

J&J Starts Phase 3 Trial for RSV Vaccine in Older Adults

 The Janssen Pharmaceutical Companies of Johnson & Johnson today announced the initiation of its Phase 3 EVERGREEN study. The study will evaluate the efficacy, safety and immunogenicity of Janssen's investigational adult vaccine against lower respiratory tract disease (LRTD) caused by respiratory syncytial virus (RSV), when compared with placebo in approximately 23,000 adults aged 60 years and older throughout North America and a selection of countries across Europe, Asia and the Southern Hemisphere.

The EVERGREEN study was initiated based on positive results from the Phase 2b CYPRESS study, the first large study evaluating the efficacy and safety of Janssen's investigational RSV vaccine against RSV-associated LRTD in vaccinated adults aged 65 and older in the United States.

Efficacy and immunogenicity data from the Phase 2b CYPRESS study will be presented at the virtual IDWeek 2021 taking place from September 29 – October 3 (Abstract #1106286).

Older adults are at high risk of developing a serious infection from RSV, a highly contagious, potentially life-threatening respiratory virus affecting more than 64 million people worldwide in a typical year, across all age groups.1

In September 2019, the U.S. Food and Drug Administration granted Breakthrough Therapy Designation for Janssen's investigational RSV adult vaccine for the prevention of LRTD caused by RSV in adults aged 60 years or older. This was based on clinical data indicating the potential for substantial improvement compared to available standard of care on a clinically significant endpoint(s). In November 2020, the European Medicines Agency's Committee for Medicinal Products for Human Use designated Janssen's investigational RSV adult vaccine as eligible for the priority medicines (PRIME) scheme based on promising clinical data and an unmet need for a prophylactic option to prevent RSV in older adults.

https://www.kpvi.com/news/national_news/janssen-announces-start-of-phase-3-trial-for-investigational-respiratory-syncytial-virus-rsv-vaccine-in/article_47114553-9c49-5f66-ac89-768b0b8afe8a.html

NuCana Soars as FDA Fast Tracks Potential Drug for Biliary Tract Cancer

 NuCana stock (NASDAQ:NCNA) climbed 22% in Wednesday’s premarket trading as the Food and Drug Administration fast-tracked the company’s experimental drug for treatment of biliary tract cancer.

The drug, acelarin, is currently being evaluated in a phase-III study for the first-line treatment of patients.

The FDA's announcement means that company and regulator will now stay in constant touch throughout the entire drug development and review process. This will ensure quick resolution of questions and issues to eventually result in earlier drug approval and access by patients, assuming the drug meets FDA norms.

A drug is fast tracked when no previous treatment exists or when the proposed solution has proven to be better than the available therapy.

The biliary tract comprises the gallbladder and interconnecting ducts responsible for the transport of bile from the liver to the gallbladder and small intestine. Approximately 178,000 new cases of biliary tract cancer are diagnosed each year worldwide, with more than 18,000 of those diagnoses in the U.S.

https://finance.yahoo.com/news/nucana-soars-fda-fast-tracks-084640047.html

FDA Expands Lilly Erbitux Label With Braftovi For Colorectal Cancer

 Eli Lilly and Co. (LLY) said that the U.S. Food and Drug Administration has granted approval of a new indication for Erbitux or cetuximab injection in combination with Braftovi or encorafenib, marketed by Pfizer, Inc., for the treatment of adult patients with metastatic colorectal cancer with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy.

Erbitux is the first and only anti-EGFR antibody approved, in combination with encorafenib, for this indication and is based on results from Pfizer's BEACON CRC trial, the only Phase 3 trial to specifically study patients with previously treated metastatic colorectal cancer with a BRAF V600E mutation.

With this approval, Erbitux has now received seven FDA approvals to treat certain types of colorectal cancer and squamous cell carcinoma of the head and neck.

The BEACON study showed that the combination of Erbitux and encorafenib significantly improved overall survival in patients with metastatic colorectal cancer with a BRAF V600E mutation - a subtype that typically has worse outcomes compared to those without the mutation.

The labeling for Erbitux includes warnings and precautions for infusion reactions, cardiopulmonary arrest, pulmonary toxicity, dermatologic toxicity, hypomagnesemia and accompanying electrolyte abnormalities, and embryo-fetal toxicity.

On April 8, 2020, Pfizer's encorafenib was approved by the FDA for this indication, based on data from the BEACON colorectal cancer study.

https://www.nasdaq.com/articles/fda-expands-lillys-erbitux-label-with-braftovi-for-treatment-of-metastatic-colorectal

AstraZeneca to Buy Remaining Stake in Caelum Biosciences for $150M

 AstraZeneca PLC said on Wednesday that it will acquire the remaining equity in Caelum Biosciences Inc. for $150 million upon completion.

Caelum is developing CAEL-101, an antibody used for the treatment of light chain amyloidosis, a rare disease which can cause significant organ damage and failure.

The London-listed biopharmaceutical company said that Alexion, its rare diseases division, will pay Caelum Biosciences the agreed option exercise price for its remaining equity, and that the transaction has potential for additional payments of up to $350 million upon regulatory and commercial milestones being achieved.

AstraZeneca said it will advance and accelerate the Phase 3 clinical development of CAEL-101.

"With a median survival time of less than 18 months following diagnosis, there is an urgent need for new treatments for this devastating disease. CAEL-101 has the potential to be the first therapy to target and remove amyloid deposits from organ tissues, improve organ function, and, ultimately, lead to longer lives for these patients," Alexion Chief Executive Marc Dunoyer said.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/AstraZeneca-to-Buy-Remaining-Stake-in-Caelum-Biosciences-for-150-Million-36543180/

FDA leaning toward approving Moderna half-dose booster

 The U.S. Food and Drug Administration (FDA) is leaning toward authorizing half-dose booster shots of the Moderna Inc COVID-19 vaccine, Bloomberg News reported https://bloom.bg/3EXGHjA on Tuesday, citing people familiar with the matter.

The FDA had been seeking information about the effectiveness of a full third dose of the Moderna vaccine, but is now ready to move forward and consider the half-dose booster Moderna has proposed, the report said.

Moderna and the FDA did not immediately respond to Reuters request for comment outside regular business hours.

Moderna on Sept. 1 submitted its application to the U.S. Food and Drug Administration seeking authorization for a booster shot.

The original Moderna vaccine contains 100-micrograms of mRNA in each shot. The company's submission to regulators to authorize a half-dose booster would allow Moderna to produce more.

https://news.yahoo.com/u-fda-leans-toward-nod-025048820.html