Pulmonary hypertension in the family - Wicked Local Watertown

Pulmonary hypertension in the family - Wicked Local Watertown
PAH Candidate Sotatercept Granted FDA's Breakthrough Therapy Status - Pulmonary Hypertension News
NORD Webinar Outlines COVID-19 Response on Financial, Policy Fronts - Pulmonary Hypertension News

Posted: 19 Apr 2020 12:00 AM PDT

Question: My sister died of pulmonary hypertension. Does this run in families?

Answer: Pulmonary hypertension (PH) is a serious disease, affecting up to 100 or more per 100,000 people, and is more common in women than men. There are many causes, and only a small percentage of cases are familial.

PH is when the blood pressure in the arteries of the lungs is elevated to over 25 mmHg at rest; normal is 8 to 20 mmHg. It is thought that this may be caused when something happens to the layer of cells that line the blood vessels in the lungs. These vessels then scar and so blood does not flow easily through them. It is vital that blood get to the lungs to be recharged with oxygen, and so the body reacts to this inhibited flow by increasing the blood pressure to push the blood through these compromised vessels. The need for this high blood pressure also puts a severe strain on the right side of the heart, since the right side of the heart is responsible for pumping the blood to the lungs (the left side of the heart pumps the blood around the body), causing right-sided heart failure to develop.

PH is classified by the cause, being primary PH (PPH) or being due to one or more contributing conditions (data from the PH Association):

Group 1, primary pulmonary hypertension (PPH), is diagnosed in about 5% of all PH cases and is when the primary cause seems to be some mechanism in the arteries themselves, whether from an inherited condition (10% of Group 1 cases), from toxicity to a drug or toxin, due to a systemic connective tissue disease such as scleroderma, lupus or other, due to an infection such as HIV or others, due to a liver disease causing portal hypertension such an infection or other causes, or due to some other condition.
Group 2, contributing to around two thirds of cases, is when PH occurs secondary to a condition in the left side of the heart.
Group 3, contributing to about 10% of cases, is when PH is due to some chronic lung disease that causes chronic low oxygenation.
Group 4, identified in less than 5% of cases, is when PH is due to repeated blood clots blocking some of the arteries in the lungs.
Group 5 is when PH is due to unclear causes, and is diagnosed in about 15% of cases.

Most patients with PH present with increasing shortness of breath on exertion, chest pain, fainting, or fatigue, and in more advanced cases symptoms from the right side of the heart being compromised such as leg swelling or other symptoms. These symptoms are not specific to PH and may occur from many other diseases, making the diagnosis of PH challenging. On a physical exam your doctor may appreciate signs of right-sided heart failure, which include changes in your heart sounds (an increased P2) as well as certain heart murmurs (pulmonic regurgitation or the Graham Steell murmur).

The evaluation for PH will include checking for other conditions that may be associated with it (see above), including blood tests, lung function tests, a chest CT and/or other tests. An echocardiogram will help verify the diagnosis, and a right sided heart catheterization may be indicated to check the actual pressures involved. Occasionally a lung biopsy may be needed as well.

About half of PH patients die within three years if left untreated. Treatment is aimed at addressing the underlying condition, and the prognosis for these patients is determined by the prognosis for the underlying condition and how severe the PH is at diagnosis. Advanced treatments that directly address the increased pulmonary high blood pressure, such as with certain medications that dilate these vessels or with other treatments, may be indicated for Group 1 patients and sometimes for patients in other Groups when other treatments are not helping.

Unfortunately, even with aggressive treatment, about one-third of PH patients die within 5 years. Risk factors for a poor prognosis include age over 50, failure to respond to initial treatments, as well as other factors. Lung transplantation may improve survival for some patients.

There is research being done to better understand this devastating disease, and new treatment options are being sought. For now the best thing is to seek care from a doctor who specializes in this disease to improve the patient's quality of life as well as improve their overall survival.

Jeff Hersh, Ph.D., M.D., can be reached at DrHersh@juno.com.

PAH Candidate Sotatercept Granted FDA's Breakthrough Therapy Status - Pulmonary Hypertension News

Posted: 13 Apr 2020 12:00 AM PDT

The U.S. Food and Drug Administration (FDA) has granted the designation of breakthrough therapy to Acceleron Pharma's investigational molecule sotatercept for the treatment of pulmonary arterial hypertension (PAH).

Breakthrough designation is given to medications that have the potential to provide significant advantages over currently available options. It is intended to accelerate the development, review, and approval of treatments for serious or life-threatening conditions.

This designation follows sotatercept's inclusion in the FDA's orphan drug program in 2019 which, among other incentives, provides a seven-year period of marketing exclusivity if the treatment receives regulatory approval.

"[W]e're thrilled that the FDA has granted this Breakthrough Therapy designation — a first for an Acceleron-discovered medicine and for a therapeutic candidate in PAH — as it supports and aligns with our mission to deliver novel therapeutic options to patients in need as quickly as possible," Habib Dable, president and CEO of Acceleron, said in a press release.

Sotatercept is an investigational compound that works to counteract the abnormal bone morphogenic protein (BMP) signaling in the lungs, believed to be a critical driver of the vascular remodeling processes that contribute to PAH development and progression.

It does so by binding and trapping proteins of the transforming growth factor-beta (TGF-beta) family — which control numerous aspects and effects of cell functions — especially those directly involved in the BMP pathway.

By restoring the balance of BMP signaling, sotatercept is believed to improve the health of pulmonary arteries and reduce pulmonary arterial pressure, ultimately lowering the risk of heart failure.

An ongoing Phase 2 trial, named PULSAR (NCT03496207), is assessing the safety and efficacy of sotatercept as an add-on treatment for people with PAH.

The double-blind trial enrolled 106 participants, who were randomly assigned to receive one of two doses of sotatercept — 0.3 or 0.7 mg/kg — or a placebo, while continuing their standard of care therapies. Treatment was given once every three weeks via a subcutaneous (under-the-skin) infusion, for a total of 24 weeks (about six months).

The trial's main goal was to demonstrate whether sotatercept is better than placebo at reducing pulmonary vascular resistance — a measure of heart strain assessed through right heart catheterization — after six months.

That goal was met, according to topline data announced earlier this year, along with several other secondary endpoints of PULSAR. In addition to inducing a significant drop in patients' heart strain compared to placebo, sotatercept also significantly improved the patients' exercise tolerance (a key secondary measure), reduced disease severity, and lowered markers of heart failure.

Sotatercept was generally well-tolerated, and had a safety profile consistent with previous reports. Detailed results from the study will be presented at a medical meeting later this year.

"In January of this year, we reported positive topline results from our PULSAR Phase 2 placebo-controlled trial of sotatercept in patients with PAH," said Dable. "Based on the results, we believe that sotatercept has the potential to shift the current treatment paradigm, and provide significant benefit to patients with PAH on top of currently available therapies."

Apart from PULSAR, Acceleron is also conducting another Phase 2 study, called SPECTRA (NCT03738150), assessing sotatercept in PAH patients.

NORD Webinar Outlines COVID-19 Response on Financial, Policy Fronts - Pulmonary Hypertension News

Posted: 30 Apr 2020 08:00 AM PDT

As the number of Americans infected with COVID-19 surpasses one million, it's no surprise that people with rare diseases — whose immune systems were generally compromised even before the outbreak — are particularly terrified of this pandemic.
That fear is evident in an online survey conducted by the National Organization for Rare Diseases (NORD), an umbrella coalition of some 280 rare disease patient advocacy groups.

About two-thirds of the 772 people who responded are rare disease patients; the rest are caregivers. Three-fourths of those who took part in the survey are age 40 or older, said Vanessa Boulanger, NORD's director of research.
Boulanger spoke April 21 during a half-hour webinar that also featured three other NORD officials: Jill Pollander, director of patient services; Rachel Sher, vice-president of policy and regulatory affairs; and Katie Kowalski, senior manager of education programs.
Initial findings show that 98% of survey participants are afraid of catching COVID-19 (with 67% saying they are "very" or "extremely" worried).
In addition, 95% of respondents have been affected to some degree by the pandemic, and 60% worry about shortages of medication and medical supplies.
The poll also showed that:

39% have had challenges accessing medical care or treatment
74% had medical appointments canceled due to COVID-19
59% have been offered phone or video calls as alternatives to in-office appointments
29% have lost jobs temporarily or permanently due to COVID-19
40% of households have been affected by loss of income
11% of job losses also have resulted in loss of health insurance

"I think this crisis underscores the critical need for standardized measures," said Boulanger, adding that this is the first in a series of surveys NORD is conducting in order to address the rare disease community's biggest concerns. "There's also an opportunity to re-envision clinical trial design, which may reduce geographic and time-related barriers for patients. Virtual design may also present new opportunities for rare-disease patients moving forward," she said.

NORD offers advice, financial aid

NORD's webinar took place as the number of people infected worldwide surpassed 2.5 million, making this the worst pandemic in more than a century. As of April 22, the disease had infected more than 800,000 Americans and killed nearly 45,000 — with the U.S. accounting for more than a quarter of the world's total deaths.
Pollander said NORD currently fields an average 1,148 emails and 1,736 phone calls per week.

"We answer lots and lots of questions, some related to coronavirus and living through this pandemic, and others more typical of living with rare diseases in general," she said. "We are not providers of care, but we can help patients maneuver through this obstacle course."
Pollander added: "We're asked to decipher a plethora of information circulating online. Lots of websites, links and webinars are out there, but for reliable, user-friendly information that's all in one place, visit the NORD landing page with current, reliable and reputable content."
On April 15, NORD established its COVID-19 Rare Disease Critical Needs Non-Medical Assistance Fund, which provides financial aid to rare disease patients who qualify.
"We are committed to providing immediate help for the things that many of our community members so desperately need — things like travel, lodging, rent and mortgage payments, utilities, support during school closures and emergency repairs to cars, homes and appliances," Pollander said.
Assistance is based on eligibility and available funds. Review criteria includes: confirmation of a rare disease diagnosis; evidence that the need is driven by the COVID-19 pandemic; financial eligibility and confirmation that the aid requested is consistent with non-medical program criteria.
"Life is challenging enough these days, so we try to make the applications as easy as possible," Polander said. "In a phone call that can take 10 minutes, we can determine if you're eligible for assistance, and move forward from there."
NORD's RareCare network currently covers 57 rare diseases ranging from acute lymphocytic leukemia to Zellweger spectrum disorders. It has active programs in all 50 states and the District of Columbia, with 6,025 people enrolled in such programs this year.
For more specific information on the fund, call NORD at 203-242-0497, or send an email to [email protected].

Getting Congress to act

But NORD also is active on the legislative front, Sher said.
"Our policy team has been extremely active since the beginning of the coronavirus crisis," she said. "As we all know, social distancing has had some particularly challenging effects, and access to healthcare for patients who have been told to stay home is a major concern."

Among other things, the coalition has written to Congress, asking key Democrats and Republicans to remove burdensome barriers to obtaining medications so they can avoid hospitals and doctors' offices.
"It is a particular concern to maintain a consistent supply for people who take an approved medication that is being studied for use in COVID-19, such as hydroxychloroquine, which is used to treat lupus and rheumatoid arthritis," said a March 20 letter signed by NORD and 94 other nonprofit groups.
"So far, CMS [Centers for Medicare & Medicaid Services] has encouraged flexibility in Medicare, and states have flexibilities through 1135 waivers to relax refill limits," the letter reads. "However, implementation is uneven, and plans and states cannot relax controlled substance guidelines on their own. Congress must take immediate, national action to ensure access to medications."
According to Sher, "for patients who obtain critical infusion therapies, it's become necessary to get treatments at home instead. But for many, there have been impediments to getting insurance. Some private and public health insurers have placed limits on refills, so we're calling on congressional leaders to expand refill access during this crisis."
Sher said NORD also has been working to ease state licensing restrictions on telemedicine, thereby reducing the need for rare-disease patients to travel to see their doctors.
"We've all heard concerns about hospital systems becoming overwhelmed. States and hospitals have been trying to develop guidelines on triage in the event critical lifesaving equipment becomes scarce," she said. "For the rare disease community, this is a frightening prospect indeed."
NORD's webinar series are funded by Sanofi Genzyme, Biogen, Horizon Therapeutics and Strongbridge Biopharma.
The next webinar, set for May 5 at 2 p.m. EST, will feature Rishi Desai, MD, on testing and treatments for COVID-19, as well as the search for a vaccine.

Search This Blog

Pulmonary Hypertension