1. Brief Description of Patient Group(s) Supplying Input

Input was received from two patient groups. The submission was developed jointly by both organizations.

The Pulmonary Hypertension Association of Canada (PHA Canada) is a federally registered charity established by patients, caregivers, and health care professionals whose goal is to empower the Canadian pulmonary hypertension (PH) community through awareness, advocacy, education, research, and patient support. PHA Canada receives funding from members of its Standing Corporate Committee, which consists of pharmaceutical companies (including Actelion). Funding is provided through membership dues and grants. The Board Chair, who helped prepare the submission, has received consulting and speaking fees, research grants, and investigator fees from pharmaceutical companies, including Actelion.

The Scleroderma Society of Canada (SSC) is the national organization representing all scleroderma organizations and groups in Canada. The SSC works to improve the quality of life of those with scleroderma through promoting public awareness, supporting those affected by scleroderma, and funding research to find a cure. The SSC has received unrestricted funding from pharmaceutical companies, including Actelion. The SSC made no statement with regard to potential conflicts of interest for the individuals who prepared the submission.

2. Condition-Related Information

Information for the submission was gathered through telephone interviews with three patients who had experience with Uptravi as part of the GRIPHON clinical trial, and an online survey of pulmonary arterial hypertension (PAH) patients and caregivers (available March 21 to April 6, 2016), which was completed by 94 PAH patients, 21 caregivers, and three parents of pediatric PAH patients. Additional information was obtained from PHA Canada’s 2013 Burden of Illness Survey, the Canadian Scleroderma Research Group’s patient registry, previous CADTH submissions, and stories collected through each organization’s work.

PAH is a form of PH caused by a narrowing of the pulmonary arteries of the lungs. PAH is a common complication of scleroderma and can be very severe in patients affected by this progressive connective tissue disease. PAH has a significant impact on the lives of patients and caregivers, and can affect patients’ ability to work, raise a family, and participate in everyday activities. Of the patients surveyed, 87% to 90% reported fatigue and difficulty breathing upon exertion, while one-third of patients reported swelling of feet, ankles, or belly; chest pain; fainting or light-headedness; heart palpitations; and coughing.

One patient remarked:

“I have always been an active person; it was hard for me to sit down. Now I have to space out my activities. If I do too much on one day, I pay for it the next. I am still able to take care of myself, to do laundry, go grocery shopping, and take care of the cooking, but I am not able to clean my house anymore.... It’s hard to stay positive. It’s difficult because you don’t know how much longer you have to live.”

Most patients surveyed reported limitations to recreational activities (88%), household chores (76%), and travel (74%). More than half of patients reported decreased income as a result of PAH, and 43% were no longer able to work. Half of the patients reported social isolation. Patients commonly experience depressed mood, anxiety, feelings of helplessness and hopelessness, and may also face social stigma because they do not appear sick when resting or seated. Women have to give up their dreams of becoming pregnant, as pregnancy is contraindicated in those with PH.

Caregivers are often the main support for patients, taking on the brunt of the work around the home (including caring for any children), often while being sole financial providers. They attend medical appointments, help to administer medication and manage side effects, and give much of their personal time. Many caregivers also feel isolated from society and face “burnout.” Relationships may be strained and the prospect of losing a loved one places a heavy burden on everyone.

3. Current Therapy-Related Information

There are currently nine Health Canada–approved therapies available in Canada to treat PAH, including six oral drugs: ambrisentan (Volibris), bosentan (Tracleer), macitentan (Opsumit), sildenafil (Revatio, Viagra), tadalafil (Adcirca, Cialis), and riociguat (Adempas); and three infusion therapies: epoprostenol (Flolan), treprostinil (Remodulin), and thermostable epoprostenol (Caripul). Responses to PH monotherapy are often limited, such that many patients require two or more PH medications used concurrently. This is especially true for patients with more advanced, moderate-to-severe PH. For patients with pre-existing and ongoing damage to the vascular system and fibrosis (i.e., scleroderma), PAH treatment is especially complicated and quality of life is profoundly affected.

Among the survey respondents, the most common treatments (alone or in combination) were bosentan (35%), sildenafil (35%), or tadalafil (31%), macitentan (22%), or an infusion therapy (approximately 30%). Most patients reported some benefit from current therapies, including improving breathing on exertion (somewhat effective: 60%, highly effective: 20%), improving fatigue (somewhat effective: 56%, highly effective: 8%), or improving breathlessness at rest (highly effective: 31%). In terms of disease progression, 35% felt current treatments were somewhat effective, while 25% reported high effectiveness and another 22% reported no effectiveness.

The available treatments are associated with a number of adverse effects than can affect patients’ quality of life. The adverse events most frequently cited by the PAH patients surveyed included headaches (52%), digestive problems (45%), sleeping difficulties (44%), nausea and/or stomach pain (42%), and stuffy/runny nose (42%), flushing, fainting, or dizziness (33%).

Barriers to accessing treatments also exist, and one-quarter of patients surveyed reported difficulties in accessing their current PAH therapies due to lack of access to a PH specialist close to home; paying out of pocket for supplies necessary to administer treatment; and relying solely on a manufacturer’s compassionate access program. Initial approval for combination and/or dual therapies can be difficult to obtain, which adds additional stress on patients and their families. Co-payments may not be affordable due to the high cost of treatments. Treatments to manage adverse effects of therapy may be expensive and may not be covered by government programs.

While treatments may help control symptoms and stabilize their condition, they are not a cure, and patients face the prospect of more complex and invasive medications, possible lung transplantation, and shortened life expectancy. One-third of respondents identified both disease progression and the physical impacts of PAH as areas not being addressed by current treatments, and at least half stated that their symptoms (breathing difficulties, fatigue) or social or psychological needs are not being adequately addressed by treatments.

4. Expectations About the Drug Being Reviewed

Patients and caregivers stated that oral therapy with selexipag offers advantages over injectable treatments in terms of treatment burden, and they are willing to tolerate serious adverse effects (especially scleroderma patients) if selexipag slows disease progression or improves quality of life.

Of the four patients with prior experience with selexipag (three telephone interviews, one survey respondent), all reported positive experiences with the drug. This included reduced shortness of breath and fatigue, more stamina, and improved ability to be active. One patient reported substantial improvements that allowed her to resume many activities, while another patient stated that her symptoms stabilized for one year, but she later needed to switch to treprostinil and then underwent a double-lung transplant. Another patient reported having to persevere through serious adverse effects at the start of therapy but thought the benefits outweighed the negative effects.