Are the PAD Interventions for Men Safe in Women?

 Because women are underrepresented in clinical trials evaluating endovascular therapy with stent implantation and bypass surgery for symptomatic femoropopliteal peripheral artery disease (PAD), interventionalists have scant clinical evidence on which approach is best for their female patients. 

Now, a pooled analysis of data from the REVIVE study has shown that both procedures have similar outcomes in women and men, with endovascular therapy having an edge in some metrics.

"In patients with symptomatic PAD involving the femoropopliteal segment, endovascular therapy with stent implantation vs bypass surgery was associated with a similar rate of 2-year major adverse limb events and amputation-free survival, but a lower rate of complications and significantly lower lengths of hospitalization, regardless of sex," Serdar Farhan, MD, assistant professor at the Icahn School of Medicine at Mount Sinai in New York City, reported here at the Society for Cardiovascular Angiography and Intervention (SCAI) 2024 Scientific Sessions.

"This pooled analysis of individual patient data further supports the efficacy and safety of endovascular therapy with stent implantation as an alternative to bypass surgery in both women and men," he said.

The analysis drew on individual patient data for 639 participants in the REVIVE study.

The data came from five randomized controlled trials comparing the two procedures; of the participants, 185 (29%) were women. 

The goal, Farhan said, was to evaluate 2-year rates of major adverse limb events and other key outcomes such as amputation-free survival and primary patency. Shorter-term endpoints were 30-day complications related to a composite of bleeding, infection, and death as well as bleeding and infection as singular findings.

Where Are the Women in PAD Trials? 

"Women are underrepresented in PAD revascularization trials and, so far, no robust data exist on sex-specific outcomes related to revascularization strategy," Farhan said when he presented the results. "The optimal revascularization strategy for women with symptomatic PAD remains unknown, and the treatment recommendations are mainly based on clinical trial data, which predominantly enrolled men." 

At 2 years, the rates of major adverse limb events with endovascular therapy and bypass surgery were not significantly different for the two sexes, at 40.6% and 42.1% (P = .764), respectively, in women and at 39.7% and 34.4% (P = .963), respectively, in men. 

Rates of major adverse limb events, individual components of major adverse limb events, and primary patency were similar for the two procedures, regardless of sex. Endovascular therapy had significantly lower 30-day complication rates than did bypass surgery — 8.7% vs 25.9% (P = .002) in women and 5.9% vs 21.5% (P = .770) in men — along with significantly shorter hospital stays for both women (3.7 ± 5.7 vs 7.2 ± 4.2 days; P = .001) and men (2.8 ± 3.2 vs 7.4 ± 5.1 days; P = .001).

Farhan also reported 23 cases of technical failure in the endovascular arms — a rate of 2.9% (n = 3) for women and 9% (n = 20) for men — whereas none were reported in the bypass surgery arms.

Other key outcomes of endovascular therapy vs bypass surgery were: 

• A composite of bleeding, infection, and death: 8.7% vs 25.9%, respectively, in women (P = .002) and 5.9% vs 21.5%, respectively, in men (P < .001)
• Bleeding: 5.8% vs 14.8%, respectively, in women (P = .04) and 4.5% vs 8.2%, respectively, in men (P < .11)
• Infection: 2.9% vs 16%, respectively, in women (P = .001) and 0.9% vs 15%, respectively, in men (P < .001)
• Death: 1% vs 0%, respectively, in women (P = NA) and 0.5% vs 0.4%, respectively, in men (P < .96).

"Ideally, this means an operator has the choice to offer two strategies to the patient that are similarly effective," Farhan explained after his presentation.

"Interestingly, we saw that the composite of bleeding, infections, or death within 30 days is significantly less with endovascular therapy in both sexes," he added, noting that the rate of bleeding in women who had endovascular therapy was one third the rate in those who had bypass surgery, whereas in men, the bleeding rate with endovascular therapy was half that of bypass.

"It means that there might be a signal toward a lower risk of bleeding in the early phase in women than in men when we apply endovascular therapy with stent implantation instead bypass surgery," Farhan added. "However, we need larger studies to validate this."

Call for Broader Studies

This pooled analysis of REVIVE data reinforces the efficacy and safety of endovascular therapy for PAD for both sexes, said Ethan Korngold, MD, chair of structural and interventional cardiology at Providence Health Institute in Portland, Oregon.

However, he added, future studies of endovascular therapy for PAD should broaden their scope.

"It's notable that this trial focused on patients treated with stents," Korngold said. "I would love to see future research focus on other techniques that we use to treat PAD, whether it's drug-coated balloons or atherectomy, just to encompass the full range of endovascular treatments, but it's very encouraging that both sexes benefited from it and both did very well."

That focus on one specific therapy is perhaps the study's primary limitation, he said. "But I think these are great data, and we need to be doing more of this type of research to see the patients that we're reaching and to see how they benefit from this," Korngold added.

https://www.medscape.com/viewarticle/are-pad-interventions-men-safe-women-2024a1000ape

Biomea Fusion BMF-219 in Diabetes Placed on Clinical Hold

 Biomea Fusion, Inc. (“Biomea” or the “Company”) (Nasdaq: BMEA), announced that the Company has received notice from the U.S. Food and Drug Administration (FDA) that a full clinical hold has been placed on Biomea’s ongoing Phase I/II clinical trials of the Company’s investigational covalent menin inhibitor BMF-219 in type 2 and type 1 diabetes (COVALENT-111 and COVALENT-112), respectively. The Company will continue ongoing safety and efficacy data collection during the hold.

“We respect the FDA’s decision and agree that patient safety is paramount and our top priority. We are fully collaborating and working diligently with the FDA to put a plan in place as quickly as possible to ensure patient safety and look forward to resuming the studies once we have authorization from the FDA. The results to date have supported that BMF-219 is generally well-tolerated and can restore glucose-controlled insulin production and improve glycemic control. Based on the totality of the safety and efficacy data for BMF-219 in diabetes to date, we remain committed to advancing BMF-219 with its potentially transformative profile,” stated Thomas Butler, Biomea Fusion’s Chief Executive Officer and Chairman of the Board.

The FDA cited deficiencies based on the level of possible drug-induced hepatotoxicity observed in the completed Dose Escalation Phase of COVALENT-111. During the Dose Escalation studies, higher doses (up to 400 mg), various food intake regimens, medical history and concomitant medications may have contributed to observed liver enzyme elevations. As previously reported, the majority of adverse events (AEs) have been mild to moderate in nature and no serious adverse reactions (SARs) have been reported to date with BMF-219 in COVALENT-111 and COVALENT-112.

https://www.globenewswire.com/news-release/2024/06/06/2895065/0/en/Biomea-Fusion-Announces-BMF-219-in-Diabetes-Placed-on-Clinical-Hold.html

QIAGEN to discontinue NeuMoDx integrated PCR testing system, support customers during transition

 

NeuMoDx 96 and NeuMoDx 288 Molecular Systems decision taken in light of challenging post-pandemic market development trends // Reaffirms Q2 2024 outlook, raises full-year 2024 outlook for adjusted diluted EPS to $2.14 CER, has started discussions with NeuMoDx customers to assess impact on 2024 sales // Restructuring charge of approximately $400 million – including about $300 million of non-cash charges – planned to be recognized primarily in 2024

https://www.globenewswire.com/news-release/2024/06/06/2895056/8690/en/QIAGEN-to-discontinue-NeuMoDx-integrated-PCR-testing-system-support-customers-during-transition-period.html

Waystar prices IPO at $21.50 midpoint

 Waystar Holding Corp. ("Waystar") today announced the pricing of its initial public offering of 45,000,000 shares of its common stock at a price to the public of $21.50 per share. Waystar granted the underwriters in the offering a 30-day option to purchase up to an additional 6,750,000 shares of common stock at the initial public offering price, less the underwriting discount. The shares are expected to begin trading on The Nasdaq Global Select Market ("Nasdaq") on June 7, 2024, under the symbol "WAY." The offering is expected to close on June 10, 2024, subject to customary closing conditions.

Waystar intends to use the net proceeds from the offering to repay outstanding indebtedness.

J.P. Morgan, Goldman Sachs & Co. LLC, and Barclays are acting as joint lead book-running managers of the offering and as representatives of the underwriters for the offering. William Blair, Evercore ISI, BofA Securities, RBC Capital Markets, and Deutsche Bank Securities are acting as joint bookrunners for the offering. Canaccord Genuity and Raymond James are acting as co-managers for the offering.

https://www.prnewswire.com/news-releases/waystar-announces-pricing-of-initial-public-offering-302166624.html

Seres, indebted and in need of cash, agrees to sell microbiome pill to Nestle

 

• Seres Therapeutics plans to sell all the rights to its microbiome pill to Nestlé Health Science as it struggles to fund operations.

• Under a nonbinding memorandum of understanding announced Thursday, the Swiss company will acquire all the product and intellectual property rights to Vowst, which was approved in the U.S. in 2023 to prevent the recurrence of difficult-to-treat C. diff infections. Seres expects the transaction to close within 90 days.

• The company didn’t disclose exact financial terms for the deal, saying only that it would receive capital infusions including an upfront payment. Seres said it will use the money to retire an existing debt facility with Oaktree Capital Management and extend its cash runway into the fourth quarter of 2025.

The sale will allow Seres to focus on advancing SER-155 and other experimental microbiome therapies designed to fight infections. In April, the company announced it had completed patient enrollment for a Phase 1b trial of SER-155 in patients who received allogeneic hematopoietic stem cell transplants.

Seres has been working with Nestlé since 2016 when the companies signed a development and commercialization deal involving four medicines. In 2021, Nestlé agreed to pay Seres to expand the collaboration and acquire more commercialization rights to one of those drugs, SER-109, now sold under the brand name Vowst.

The pill is made from human fecal matter that’s been screened and purified. It’s designed to repopulate the gut with helpful bacteria to ward off infections. It was the second microbiota therapy to win Food and Drug Administration approval and the first one cleared for oral administration. But a year after the launch of Vowst, Seres is struggling. The company posted a net loss of $40.1 million in the first quarter and told investors in May that its cash was sufficient to carry operations only into the fourth quarter of this year. That was even after eliminating 41% of its workforce in a restructuring announced in November.

Seres said it will enter into a service agreement with Nestlé to support the transition of the product. Its new cash runway guidance is subject to performance under the service agreement.

https://finance.yahoo.com/m/4940e794-67f9-330e-91fa-c113f76b0893/seres%2C-indebted-and-in-need.html

FibroBiologics withdraws registration statement for public offering

 Securities and Exchange Commission

Division of Corporation Finance

Office of Life Sciences

100 F Street, N.E.

Washington, D.C. 20549

 

	RE:	FibroBiologics, Inc.
		Request to Withdraw Registration Statement on Form S-1
		File No. 333-278938

 

Ladies and Gentlemen:

 

Pursuant to Rule 477 under the Securities Act of 1933, as amended (the “Securities Act”), FibroBiologics, Inc. (the “Company”) hereby respectfully requests that the Company’s Registration Statement on Form S-1 (File No. 333-278938), as amended, together with all exhibits thereto (the “Registration Statement”), initially filed with the Securities and Exchange Commission (the “Commission”) on April 26, 2024, be withdrawn, effective as of the date hereof. The reason for such withdrawal is that the Company has determined not to pursue the public offering to which the Registration Statement relates and will consider other alternatives. The Registration Statement has not been declared effective by the Commission, and no securities have been issued or sold under the Registration Statement. Accordingly, withdrawal of the Registration Statement is consistent with the public interest and the protection of investors, as contemplated by paragraph (a) of Rule 477.

 

The Company requests that, in accordance with Rule 457(p) under the Securities Act, all fees paid to the Commission in connection with the filing of the Registration Statement be credited for future use.

 

Pursuant to Rule 477(c) under the Securities Act, the Company advises the Commission that it may, upon consideration of its financing needs and options, undertake one or more subsequent private offerings in reliance on Rule 155(c) under the Securities Act.

 

Pursuant to Rule 477(b), the Company understands that this request to withdraw the Registration Statement will be deemed granted as of the date hereof unless the Company receives notice from the Commission within 15 days of the date hereof that such request will not be granted. Thank you for your assistance and cooperation in this matter.

 

	Very truly yours,
	FibroBiologics, Inc. https://www.sec.gov/Archives/edgar/data/1958777/000149315224022878/formrw.htm

Inflation Reduction Act Is Bad for Oncology Medicines

 The Inflation Reduction Act makes some significant changes to the Medicare program. Notably, the law directs the federal government to intervene and set the price for certain medicines. Medicare “negotiation” starts with ten medicines already selected for price setting in 2026 and expands to twenty by 2029. This Inflation Reduction Act price intervention for drugs includes an odd selection criterion not seen in any other price-setting system outside of the United States. The IRA treats medicines made from small molecules, typically pills, differently from medicines made from large molecules, typically injections. This is particularly bad for future clinical development in the types of medicines most of us rely on, pills we can take at home, which include cancer medicines.

Small molecule medicines are made from simple chemical synthesis; they have a low enough molecular weight to pass through a cell wall, making them particularly effective for getting inside an organ like the brain or for getting in and killing a cell that is causing illness. Large molecule medicines are derived from living organisms like proteins or plasma and can attach to a cell and can cause the body to respond with its own immune system. Both types of medicines are important, and both should be evaluated on the same merits for their potential to improve patient health.

The Inflation Reduction Act selects the biggest revenue drugs for price setting, and it selects small molecules seven years after they were approved by the U.S. Food and Drug Administration (FDA) and large molecules after eleven years. With this setup, the price setting for the small molecules cuts more deeply into expected revenues for small-molecule medicines relative to large molecules. Simply put, less years on the market before the government steps in to set the price means less revenue opportunity. While this is likely an unintended consequence of the design of law, it has the effect of being more punitive to the expectation of profitability for small molecule medicines (and financial incentives to invest in expensive often unsuccessful clinical development programs). Moreover, because of technological advances that have allowed more medicines for cancer to be developed as small molecule pills which have become highly used drugs in Medicare Part D where the price setting starts, the design price setting has a large effect on oncology, which is among the biggest therapeutic classes in Medicare. By reducing the expectation of revenue from successful development of those medicines to a larger degree relative to other treatments, the Inflation Reduction Act will send investor money, which pays for clinical studies, to other types of therapies not affected by the law, or out of medicine to other business sectors.

In a recently published study my co-authors and I simulate the expected effect of the federal price setting in the Inflation Reduction Act. We examine the medicines already selected for price setting and then forecast which medicines are likely to be selected in 2027 and 2028. We find that the vast majority of medicines that will be selected are made from small molecules and that the most common therapeutic area selected is cancer treatments, followed by respiratory conditions and diabetes. We find that IRA price setting, if done conservatively at the upper limit of what the law permits, will reduce future revenues of the small molecule medicines by 28%. This will mean that there will be less investment in those medicines, particularly in post market trials which are large and expensive and often used to study medicines in people not represented in earlier stage trials including children.

Some policymakers and policy analysts have suggested that price setting will not affect clinical development. This is not consistent with the large body of evidence demonstrating that investment There is an established relationship between investment in drug development and an expectation of the financial return on that investment.  Drug development is a risky and expensive process. There are many places to place bets on science, and investors will place them on the clinical development programs most likely to transform health outcomes and earn their money back. When considering two medicines, one that has its expected revenues of $750,000 is simply less attractive than one that has expected revenues of $1 billion, particularly when there is a high likelihood that both will probably fail. The price setting system in the Inflation Reduction Act will steer investment away from drugs for conditions common in seniors and disabled people and in particular small molecules. By distorting the odds of financial success for pills, and particularly pills for cancer treatment, the Inflation Reduction Act is playing a dangerous game with the future of better health through medicine.

Kirsten Axelsen is a visiting scholar with the American Enterprise Institute and a biopharmaceutical company consultant.

https://www.realclearhealth.com/blog/2024/06/06/the_inflation_reduction_act_is_bad_for_oncology_medicines_1036431.html