When September knocks on our door, time suddenly slows down a bit. Autumn lets herself into our lives with crisper air, fresh perspective, and a few stray leaves. As the harbinger of change and transformation, it resets our inner clocks, inspiring us to reevaluate our dreams, aspirations, goals, intentions, plans, habits, and every other element on which we build our daily lives. Fall is our cue to consider starting anew. Perhaps the next phase is long overdue? The magic of new beginnings is the message of Mother Nature this particular season.
Autumn is a brilliant mindfulness teacher, so spend some quality alone time with her. While anchoring us in the present moment, this season also encourages reminiscence. Look back on your life, dive into memories for a while, find what you can feel grateful for in your past. Remember when as a kid you used to jump into heaps of dry leaves in the yard? We had a rope swing specifically set up for that purpose, It would likely be considered a danger now, but we clamored to be the first to try it out.
Along comes nostalgia, a bittersweet feeling bearing gifts images of days long gone. No matter our age, it always feels like forever ago. There are clues in these mental projections and our emotions tied to them. Maybe something is missing? Maybe there are still wounds left to heal? Or, perhaps, we simply need more childish enthusiasm and spontaneity in our adult lives? Autumn gives us plenty of awe-igniting opportunities for that.
Especially when it greets us with its vibrant colorswith plums, pears, and shades of gold glistening in the lazy, autumnal sun. Somehow, the light always seems a little more golden in the fall.With its shifting shades, autumn nudges us in novel directions, whispering signs of reassurance that steady transformation breeds overwhelming beauty and a wider perspective. Change is the only constant and fall carries it with style. Let this special time transform you, too. Now, in this moment, take action and set yourself on a path towards where you want to be
Important Insurance Dates
Open Enrollment for most health insurance plans will soon be in full swing. Open enrollment dates and the process you must follow will vary by the type of health insurance and employer.
Open Enrollment Periods
• ACA Marketplace open enrollment is November 1st to January 15th. The end date can be as early as December 15th in some states other than New York.
• Traditional Medicare annual open enrollment is usually October 15th to December 7th, while the annual open enrollment period for Medicare Advantage is January 1st to March 31st.
• Employer provided open enrollment periods vary by employer, so it is important to stay on top of deadlines and learn about the coverage options offered by employers. If an employer’s health plan is selfinsured, it is especially critical to find out if an “alternative funding program” has been implemented by the employer. Alternative funding programs can significantly limit or completely exclude patient access to specialty medications or include time-consuming obstacles causing critical delays.
There is no limited enrollment period for Medicaid or the Children’s Health Insurance Program (CHIP). If you miss open enrollment, you may have to wait until the next open enrollment period to gain access to coverage unless you have a qualifying life event that qualifies you for a Special Enrollment Period (SEP) or if your household income is below 150% of the federal poverty level (FPL) you can still enroll or change your Health Insurance Marketplace plan.
Thank you to everyone who came out to support our Walk!
Special thanks to the Bloody Awesome Coulombes who brought the numbers, the Scott Family for their auction donation, the long time Huskie Family for supporting us year after year, our fabulous Walk Committee: Patty Marck, Linda Peacock and Jessica Smith and all who came out to enjoy the day!
Corporate sponsors include Sanofii, Takeda, Stewarts Shops, Dunkin Donuts, CVS Health and Callanan Industries.
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Women and Anemia
Von Willebrand’s disease and hemophilia don’t directly cause iron deficiency, but heavy menstrual bleeding can lead to iron loss. Women with a bleeding disorder who experience heavy menstrual bleeding are at an increased risk of developing iron deficiency and anemia compared with men.
Chronic blood loss from heavy menstrual periods and gastrointestinal bleeding are well-known causes of iron deficiency. This condition occurs when the body lacks sufficient iron to produce hemoglobin, the substance in red blood cells that enables them to carry oxygen. This deficiency can lead to various health issues, ranging from fatigue to more severe conditions like iron deficiency anemia.
Initially, iron deficiency anemia can be so mild that it goes unnoticed. But as the body becomes more deficient in iron and anemia worsens, the signs and symptoms intensify.
Iron deficiency anemia signs and symptoms may include:
• Extreme fatigue
• Weakness
• Pale skin
• Chest pain, fast heartbeat or shortness of breath
• Headache, dizziness or lightheadedness
• Cold hands and feet
• Inflammation or soreness of your tongue
• Brittle nails
• Unusual cravings for non-nutritive substances, such as ice, dirt or starch
Extreme fatigue, one of the most common symptoms, can itself be very debilitating. You can think of fatigue itself as a symptom, but here are some more detailed terms to describe what it might feel like:
Lack of energy– this is a kind of mental or physical exhaustion that makes it harder to move through daily life. It can impact your ability to work, spend time with your friends or family, or do other activities.
Drowsiness– you may feel like you have to fight to stay awake but your tiredness may still be there after you sleep.
Difficulty thinking also called “brain fog,” you may have trouble paying attention, remembering things, or focusing on detail-oriented tasks.
Apathy this refers to a feeling where you lose interest or motivation to do things.
Ferritin, a blood protein that stores iron in the body, is a key indicator of iron levels. The reference value in a lab for women with low ferritin is usually around 16 ng/mL, but clinicians note that a level below 50 ng/mL is definitive for iron deficiency. Experts recommend that women with bleeding disorders have their ferritin level checked at least once a year.
Iron deficiency is not just a minor inconvenience; it’s a significant health issue that deserves attention and proper management. Regular monitoring and proactive management of iron levels are key to preventing the debilitating effects of iron deficiency.
Gene Therapy Update
Uptake of Gene Therapy Remains Slow
Although BioMarin’s valoctocogene roxaparvovec (val-rox, marketed as Roctavian) was approved in June 2023, the first patient outside of clinical trials did not receive val-rox until December 2023, at the Center for Inherited Bleeding Disorders (CIBD) in California. Just this month, BioMarin announced that it will be scaling back its efforts with regard to val-rox, with the company now mainly focusing on distributing the gene therapy in the United States, Germany, and Italy, the 3 countries in which it has been approved for use by relevant regulatory authorities and is reimbursed. UniQure and CSL Behring’s hemophilia B gene therapy, etranacogene dezaparvovec (marketed as Hemgenix), which was approved by the FDA in November 2022, has also been slow to be embraced by patients.
“We haven't seen a lot of patients dosed yet,” Steven W. Pipe, MD, a professor of pediatric hematology/ oncology at CS Mott Children’s Hospital, told CGTLive regarding Hemegenix earlier in 2024. “And I don't think that’s related to either the enthusiasm of the clinicians or the patients, but really just the mechanics of how to deliver this in the clinical space, as opposed to the research trials... We've seen that a lot of the hemophilia treatment center sites have got their components together, their infrastructure and personnel so that they can actually start delivering this in the commercial setting. And so, I'm really looking forward to seeing this making a difference in patients' lives in a real-world setting.”
Additional Study Shows Gene Therapy for Hem B Significantly Outperforms Factor IX Prophylaxis
A study of Pfizer’s Beqvez, a gene therapy infusion for adults with hemophilia B showed that participants had a 44% decrease in the number of bleeds per year and almost three-fourths of participants discontinued prophylactic factor IX therapy with no increase in bleeding. The annualized rate of bleeding for total bleeding episodes decreased by 71% after treatment with fidanacogene elaparvovec (Beqvez), while the mean annualized rate of bleeding for treated bleeding episodes was reduced by 78%, reported the authors of BENEGENE-2 trial as reported in the New England Journal of Medicine. The majority (>80%) of the participants had factor IX activity in the mild-hemophilia range for a sustained period of 15 to 24 months, a finding that shows durable efficacy similar to that observed in other trials of gene therapy for hemophilia B, the study found.
An ongoing extended follow-up study to 15 years after gene therapy will provide further insights regarding the effects of fidanacogene elaparvovec.
Next Generation Gene Therapy Research
In other gene therapy news, researchers at Children's Hospital of Philadelphia (CHOP) announced the results of a new study offering insights into the development of next-generation gene therapies to treat hemophilia A. The findings were published in the journal Nature Communications. In 2023, the U.S. Food and Drug Administration (FDA), approved the first adeno-associated virus vector-based gene therapy for the treatment of adults with severe hemophilia A. The one-time gene therapy product administered as a single dose by intravenous infusion consists of a viral vector carrying a gene for clotting FVIII. The gene is expressed in the liver to increase blood levels of FVIII and reduce the risk of uncontrolled bleeding. However, multi-year available follow up data observed that FVIII levels are not consistently durable over time.
This study, led by Lindsey A. George, Director of Clinical In Vivo Gene Therapy and an attending physician in the Division of Hematology at CHOP, marks the first time that researchers have begun to understand via a mouse model why the FDA-approved treatment isn't sustainable. The research also evaluated how an enhanced variant of factor VIII protein, FVIII-QQ, which was developed in George's lab, resolved these issues in mice and could potentially be applied to people, including those under 18, under the rationale that an improved function FVIII may normalize blood clotting at low levels of expression to permit long-lasting treatment.
In the study, researchers used a mouse model and uncovered that the clotting was not sustainable because copies of the AAV vector decreased in quantity over time in the liver, which led to a reduction in FVIII protein levels. Since a sustained level of vector is necessary to continue long-term clotting function, the drop in vector copies signaled a lack of therapeutic durability.
George and her team subsequently showed that expressing the enhanced function FVIII variant, FVIII-QQ, enabled a balanced clotting process at low levels of expression that could be sustained over time. This result is significant because it has the potential to improve the longevity of gene therapy therapeutic applicability, while reducing side effects from high AAV doses.
Gene Editing
Metagenomi, a precision genetic medicines company committed to developing curative therapeutics for patients using its proprietary gene editing toolbox, announced on September 4 data from an ongoing preclinical study designed to provide evidence supporting the potential durability and safety of the company’s hemophilia A gene editing investigational therapy, MGX-001.
The non-human participant (NHP) study involved treating three NHPs with a single intravenous dose of an adeno associated virus (AAV) containing a FVIII donor template followed 35 days later by a single intravenous dose of a lipid nanoparticle containing a novel Metagenomi nuclease and associated guide RNA, targeting the first intron of the albumin gene. Each animal received only a single dose of dexamethasone prior to the AAV and LNP doses. The NHPs also underwent a liver biopsy on Day 7 to evaluate editing and integration efficiency.
All NHPs demonstrated durable FVIII activity levels over the twelve month period. At the twelve month time point two of the NHPs had FVIII activity levels within normal/near normal range while the third NHP had FVIII activity level in the mild hemophilia range.
The study remains ongoing. Company management will participate in Chardan’s 8th Annual Genetic Medicines Conference.
Metagenomi has been beset with some recent financial and legal challenges, however. Metagenomi launched its bid to start trading on the Nasdaq Global Select Market during Borges’ tenure, initially aiming to raise $86.9 million. Ultimately, the biotech put 6.25 million of its shares up for at $15 apiece for an initial public offering (IPO) of nearly $94 million.
The market was not impressed, however, and Metagenomi’s stocks crashed nearly 31% on the day of its debut. The biotech has recently been trading at around $5.
Metagenomi currently has no clinical-stage candidates, and its IPO highlights the difficulties preclinical biotechs may face should they seek to go public. The biotech is banking its business on what it calls “the most diverse gene editing toolbox,” which it envisions will be “capable of correcting any type of genetic mutation found anywhere in the genome.”
Despite its relatively young pipeline, Metagenomi is backed by several high-profile supporters, including Bayer, which led its $275 million Series B fundraising round in January 2023. A few months earlier, in November 2022, Metagenomi entered into a gene editing partnership with Ionis, which could potentially lead to a $3 billion haul for the biotech.
But months ago, Moderna backed out of its own gene editing contract with Metagenomi. In May 2024, the mRNA specialist announced that it would return full global rights to the primary hyperoxaluria type 1 program to Metagenomi, along with other base editors and RNA-mediated integration systems. The termination was “mutually agreed” upon by the two companies, Metagenomi announced at the time, although it noted that the change was prompted by a strategic prioritization by Moderna, which will stay on as a shareholder of the biotech.
Prompted by the pull out of Moderna, several law firms have filed class action law suits against Metagenomi for alleged violations of the federal securities laws on behalf of all persons and entities that purchased shares during the biotech’s IPO.
NovoSeven shortages are potentially more consequential because of the limited number of alternatives and the wide spectrum of indications. Novoseven is indicated for the treatment of bleeding episodes and for the prevention of bleeding in cases of undergoing surgery or invasive procedures for the following patient groups: - Patients with congenital haemophilia with clotting factor VIII or IX inhibitors >5 Bethesda Units (BU) - Patients with congenital haemophilia who are expected to have a high anamnestic response to factor VIII or factor IX administration - Patients with acquired haemophilia - Patients with congenital factor VII deficiency - Patients with Glanzmann’s thrombasthenia with previous or present reaction to platelet transfusions or where platelets are not readily available - Patients with severe postpartum haemorrhage when uterotonics are insufficient to achieve haemostasis
The European Haemophilia Consortium (EHC), National Bleeding Disorders Foundation (NBDF), and World Federation of Hemophilia (WFH) are closely monitoring the situation. Although no immediate supply issues have arisen, the full impact may become apparent by late 2024.
Patients currently using these treatments are advised to consult their healthcare providers.
The EHC, NBDF and WFH have stayed in touch with NovoNordisk and are expecting more details on the stocks under quarantine, the number of vials that could potentially be shipped and used and on the timeline to go back to normal for all three drugs.
Pfizer
At the 2024 Annual Meeting of the European Hematology Association, Pfizer presented findings of its long term investigational study of Marstacimab, a novel, investigational monoclonal antibody. Pfizer reports that Marstacimab shows long-term safety and efficacy in the prevention of bleeding events in patients with hemophilia A as well as B without inhibitors, potentially adding to the toolbox for hemophilia A and representing a first of its kind therapy for hemophilia B.
Marstacimab targets the tissue factor pathway inhibitor, a natural anticoagulation protein that prevents the formation of blood clots and is administered as a onceweekly subcutaneous injection. The therapy has been granted fast-track and orphan drug status in the United States, in addition to orphan drug status in the European Union for the prevention of hemophilia bleeding episodes. If approved, the therapy would become the first once-weekly subcutaneous therapy for either hemophilia A or B. Emicizumab (Hemlibra), which also is administered subcutaneously, is only approved to prevent or reduce bleeding in hemophilia A.
Industry Update cont’d.
Guardian Therapeutics
The Royal College of Surgeons in Ireland (RCSI) University of Medicine and Health Sciences has unveiled new research that shows a new medicine, Rondaptivon pegol, could help people living with the common bleeding disorder von Willebrand disease.
Currently people with von Willebrand disease may treat the condition by increasing von Willebrand factor in their bloodstream, through drug administration, encouraging the release of factor that is stored in cells near blood vessels or by injecting it into their veins.
RCSI’s research indicated that Rondaptivon pegol, also known as BT200, makes it harder for immune system cells to bind themselves to von Willebrand factor and remove it from the blood. The end result is that the factor will stay in the individual’s bloodstream for a longer amount of time. RCSI’s new discovery will clear the way for an increase in targeted treatments aimed at people living with the condition and for other disorders of the blood.
Guardian Therapeutics is an independent biotech enterprise specialized in discovery and development of aptamer therapeutics.
Sanofi
Full results from the XTEND-Kids phase 3 study published in The New England Journal of Medicine (NEJM) in July highlights the efficacy, safety, and pharmacokinetic profile of ALTUVIIIO [Antihemophilic Factor (Recombinant), Fc-VWFXTEN Fusion Protein]. ALTUVIIIO (efanesoctocog
alfa), a first-in-class, high-sustained factor VIII replacement therapy, is approved for adults and children with hemophilia A for routine prophylaxis and on-demand treatment to control bleeding episodes as well as for perioperative management (surgery).
The pivotal XTEND-Kids study published in NEJM shows ALTUVIIIO met primary and secondary endpoints, which included occurrence of factor VIII inhibitors and annualized bleed rates (ABRs). The results show no inhibitor development to factor VIII was detected. Additionally, 82% of the children treated with once-weekly ALTUVIIIO had zero joint bleeds, demonstrating ALTUVIIIO weekly prophylaxis has the potential to provide long-term preservation of joint health.
Octopharma
Octapharma USA, Inc. announced the U.S. Food and Drug Administration (FDA) has granted orphan drug exclusivity for wilate®, von Willebrand Factor/Coagulation Factor VIII Complex (Human) Lyophilized Powder for Solution for Intravenous Injection, for routine prophylaxis to reduce the frequency of bleeding episodes in adults and children 6 years of age and older with von Willebrand disease (VWD).
The FDA Orphan Drug Designation program provides orphan status to biologics and drugs for rare diseases. Wilate® is the first von Willebrand factor (VWF) concentrate indicated for prophylactic treatment across all forms of VWD, a significant patient treatment milestone for the most prevalent bleeding disorder in the United States.
Federal Update
FDA Plans Rare Disease Innovation Hub
The Federal Drug Administration announced in July plans to establish a Rare Disease Innovation Hub. The Hub will work across rare diseases but will especially focus on products intended for smaller populations or for diseases where the natural history is variable and not fully understood, as they recognize that development of therapies for these conditions can be particularly challenging. The Hub would have three primary functions:
Serve as a single point of connection and engagement with the rare disease community, including patient and caregiver groups, trade organizations, and scientific/academic organizations, for matters that intersect Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research. The Hub will help the larger rare disease community navigate important intersections across the FDAthat affect patients with rare diseases, such as medical devices, including diagnostic tests, and combination products.
• Enhance inter-center collaboration to address common scientific, clinical and policy issues related to rare disease product development, including relevant cross-disciplinary approaches related to product review, and promote consistency across offices and Centers.
• Advance regulatory science with dedicated workstreams for consideration of novel endpoints, biomarker development and assays, innovative trial design, real world evidence, and statistical methods.
The Hub will be co-led by the Directors of CDER and CBER, in close collaboration with the FDA’s Center for Devices and Radiological Health, Oncology Center of Excellence, Office of Orphan Products Development, and Office of Combination Products.
The Hub will promote collaboration among the FDA’s existing programs in the rare disease space, including the CDER Accelerating Rare disease Cures (ARC) Program and CBER Rare Disease Program. It will also provide a forum to understand and leverage what is learned from pilot programs currently being implemented across the agency, including the Rare Disease Endpoint Advancement (RDEA) Pilot Program and the Support for clinical Trials Advancing Rare disease Therapeutics (START) Pilot Program.
The FDA anticipates holding an open public meeting this fall, which will include the establishment of a public docket, to provide further information about their vision for the Hub and receive feedback from the community to help shape the Hub’s priorities and initiatives
CMS provides ACA Marketplace navigators with record funding
The Centers for Medicare and Medicaid Services (CMS) announced the availability last month of $500 million over the next five years to navigator programs in Affordable Care Act (ACA) Marketplaces that are facilitated by the federal government.
Community-based navigators play a critical role in enrollment assistance and outreach for the record 23.3 million consumers who get coverage through ACA Marketplaces, especially for hard-to-reach vulnerable populations. The $500 million grant is the largest funding allocation CMS has ever made for navigators. In 2021, the agency restored more than $80 million in navigator funding that was eliminated under the Trump Administration.
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Thank you to Octapharma and Infucare Rx for bringing Dr. Amber Federizo and Mackenzie Fly to an informative day long in-depth seminar on von Willebrand’s disease held at the Gideon Putnam in Saratoga Springs on September 7.
