Special Access Program Research Articles

Psilocybin-Assisted Therapy for Brain Cancer Related Existential Distress: A Case-Report.

Introduction: Psilocybin-assisted therapy (PAT) has gained traction in palliative care as a treatment for existential distress in the last decade. Patients with brain cancer have been excluded from studies, yet they stand to benefit as much as other patients with cancer-related psychological distress. Case description: In this report, we discuss the case of a patient with end-of-life distress secondary to stage 4 astrocytoma that received PAT through Health Canada's Special Access Program. The patient had a positive response to PAT without adverse events. Discussion: Standard treatment for existential distress is often inefficacious and PAT is rarely available, especially for patients with brain cancer. We highlight the importance of making PAT more available as many patients with unresolved existential distress resort to medical assistance in dying without ever knowing of the existence of PAT. Conclusion: PAT was effective in partially alleviating the patient's existential distress. Access to PAT needs to be expanded urgently.

Pritelivir for the treatment of nucleoside analogue–resistant orolabial herpes simplex virus 2 in a person living with HIV

Background: Nucleoside analogue–resistant herpes simplex virus infections are increasingly observed especially in immunocompromised patients. Currently, other options for treatment such as foscarnet and cidofovir are limited by difficulty of administration and significant risk of toxicity. Our report describes use of pritelivir, a novel helicase-primase inhibitor, in the treatment of nucleoside analogue–refractory orolabial HSV-2 infection. Methods: In 2017, a 53-year-old male with HIV on therapy presented with swelling of the right upper lip and a solid lesion inferior to the right nostril. Biopsy revealed cytopathic effects and immunohistochemistry staining confirming herpes simplex virus infection. The patient received multiple treatment courses including nucleoside analogue therapy, topical and intravenous foscarnet and cidofovir, and topical imiquimod but these failed to establish a significant and durable therapeutic response. Results: A swab of the lesion tested positive for HSV-2 via PCR. Subsequent genotyping revealed a M183X mutation in UL23 expected to convey resistance to acyclovir and penciclovir. The patient was started on oral pritelivir 400 mg once followed by 100 mg daily for 27 days, obtained through Health Canada's Special Access Program, resulting in near complete resolution of the lesion. Conclusion: Pritelivir is a novel helicase-primase inhibitor that appears to be an attractive option for management of resistant herpes simplex infections due to its unique mechanism, excellent oral bioavailability, and minimal toxicity. To our knowledge, this is the first described case of treatment of nucleoside analogue–resistant orolabial herpes simplex 2 infection with pritelivir and the first documented use of pritelivir in Canada.

LGG-19. SLIPPED CAPITAL FEMORAL EPIPHYSIS (SCFE): A RARE ADVERSE EVENT ASSOCIATED WITH FGFR TYROSINE KINASE INHIBITOR THERAPY IN A CHILD

Abstract BACKGROUND FGFR tyrosine kinase inhibitors (FGFR-TKIs) are being increasingly used off-label in children with hard-to-treat tumors harboring specific FGFR alterations. We report a case of Slipped Capital Femoral Epiphysis (SCFE), an on target skeletal toxicity of a pan-FGFR TKI inhibitor, erdafitinib. METHODS Data was extracted from chart review of the patient and literature search for the use of FGFR-TKIs in children and their side effects. RESULTS A 13-year-old boy was diagnosed to have a optic pathway/ hypothalamic glioma with signs of increased intracranial pressure and obstructive hydrocephalus requiring placement of ventriculo-peritoneal (VP) shunt. Sequencing of the tumor showed FGFR1-Tyrosine kinase domain internal tandem duplication (FGFR1-KD-ITD) and was negative for BRAF mutation/ fusion. Two weeks later, he was treated for a VP shunt infection (surgical revision and 6 weeks antibiotics). He developed hypothalamic obesity with rapid weight gain and BMI >30. After a four-month delay from the initial diagnosis, he was started on erdafitinib a pan-FGFR1-4 inhibitor, through a special access program. At 12 weeks of treatment, he developed persistent knee pain. X-ray of the hips showed slipped capital femoral epiphysis (SCFE) of the right hip. Erdafitinib was discontinued and he underwent surgery with in-situ pinning of the right hip and prophylactic pinning of the left hip. MRI at the time of stopping the medication showed a 30% decrease in the size of the tumor, which has remained stable at 6 months follow up. CONCLUSIONS Based on our experience and literature review of pediatric patients who are treated with pan-FGFR TKIs, we recommend: a) monitoring both rate of weight gain/ BMI for obesity and growth velocity while on therapy and b) update the drug toxicity profile of FGFR TKIs to include skeletal toxicities and inform parents/ patients of these toxicities at the time of consent for therapy.

C.3 Retrospective study of sulthiame in treatment of pediatric epilepsy

Background: This retrospective study assessed the efficacy and tolerability of sulthiame as a treatment in children with epilepsy. In Canada, sulthiame is only available through Health Canada’s Special Access Program. Methods: Patients who received sulthiame at the Montreal Children’s Hospital from April 2012 to March 2023 were included. Patients’ medical charts were reviewed, and clinical data was extracted from neurology clinic notes and electroencephalogram (EEG) reports. Efficacy was assessed by comparing seizure frequency and frequency of EEG epileptiform abnormalities before and after initiating sulthiame, while also noting any reported changes in cognition or behaviour. Results: Sixteen patients were included (10 males, 6 females), all of whom had drug-resistant epilepsy and continuous spike-wave in sleep (CSWS) on EEG. Sulthiame starting dose ranged from 0.74 to 6.75 mg/kg/day. Improvement, either in terms of seizure control, cognition, or reduction in EEG epileptiform abnormalities, was reported in 8/16 children (50%). Two patients (13%) became seizure free, while three more (19%) had reduced seizure frequency. Three other patients (19%) had reported improvements in concentration, learning abilities or behaviour. No serious adverse event was reported. Conclusions: These data indicate that sulthiame is effective and well-tolerated in children with CSWS, regardless of the etiology and type of epilepsy.

Improving Access to Psilocybin-Assisted Therapy: Barriers, Challenges, and Recommendations

IntroductionPsilocybin-assisted therapy (PAT) has demonstrated significant potential in alleviating anxiety, depression, and psychological distress among individuals with terminal illnesses. However, numerous barriers prevent equitable access to this transformative treatment.ObjectivesThis study seeks to gather the perspectives of patients on the waitlist of PAT.MethodsSemi-structured interviews highlight the challenges faced by patients seeking PAT and their care providers and propose recommendations to enhance accessibility.ResultsThrough a case study of Roots to Thrive, a non-profit healthcare practice offering group-based PAT, obstacles such as complex application processes, fear of judgement, logistical and financial constraints, and systemic inequities are revealed. Moreover, Health Canada’s stringent control of PAT access via clinical trials and the Special Access Program (SAP) presents challenges for primary care providers and hinders the involvement of trained practitioners. The moral distress experienced by patients and providers due to delayed or denied access further emphasizes the urgency of addressing these barriers.ConclusionsAdvocates are calling for streamlined referral systems, expedited services for end-of-life patients, formal billing infrastructure, practitioner education, expanded coverage, legislative adjustments, post-therapy support, and collaboration with non-profit organizations and Indigenous Healers to promote equitable and effective PAT. By implementing these recommendations, barriers to PAT can be overcome, allowing more individuals to benefit from this therapy and find relief from the psychological distress associated with their conditions.Disclosure of InterestNone Declared

Soigner au seuil de la mort : l’expérience mystique d’un patient avec la thérapie assistée par la psilocybine

<p>Patients with serious illnesses like advanced cancer often experience existential and psychospiritual distress. Alleviating this form of pain and suffering has proven to be very challenging using conventional treatments. Psilocybin-assisted therapy (PAT) employs the psychoactive effects of psilocybin as a catalyst for a psychotherapeutic process grounded in indigenous traditions and within the context of a therapeutic mindset and environment (“set and setting”). This carefully curated experience of an altered state of consciousness can promote healing and psychospiritual growth independently of the disease trajectory. Current research supports the use of this form of therapy as a safe and effective therapeutic tool for such patients. This narrative case report, based upon and written from the perspective of the treating physician, describes the therapeutic journey of a patient with the fictitious name Martin, as he receives his diagnosis of a terminal illness, engages in PAT, and on to his deathbed. Martin was the first patient in Quebec to receive psilocybin treatment through Canada’s Special Access Program (SAP) and chose to end his life with medical assistance in dying (MAID), both done in the context of homecare and paid for in its entirety by the public healthcare system of Quebec.</p>

Evaluating the patient‐perceived impact of a neratinib special access program in an Australian community pharmacy

AbstractBackgroundIn Australia, breast cancer is the most commonly diagnosed cancer in women, and improved survival rates have placed an increased burden on the healthcare system. To better utilise community pharmacists in anticancer therapy, a medicine management service for neratinib was initiated in an Australian community pharmacy for patients with breast cancer.AimTo explore the experience and satisfaction of Australian breast cancer patients who received a pharmacist medicine management service for their neratinib treatment through a community pharmacy.MethodPatients enrolled in the neratinib special access program were invited to complete an electronic survey between February–September 2019. A mixed‐methods approach was utilised in data analysis. Ethics approval was granted by the University of Canberra Human Research Ethics Committee (Project No: 20181648).ResultsThirty‐three individuals completed the survey. A majority of participants (94%) were either ‘very satisfied’ or ‘satisfied’ with the time the pharmacist spent with them. As part of the service, 88% of participants viewed the first pharmacist session as ‘absolutely’ worthwhile and 79% believed that the pharmacist interaction increased their understanding of neratinib therapy. Many participants supported the continued provision and expansion of the service (88%).ConclusionThis pilot study provided valuable insights into participants' experiences of a pharmacist medicine management service for neratinib therapy. The unique preferences and health information needs of patients were highlighted. Further investigation is needed to explore how community pharmacists may be best utilised to improve breast cancer care and support patient needs.

Retrospective review of 250 gallium-68 PSMA scans in prostate cancer patients in Health Canada Special Access Program.

e17035 Background: Prostate Cancer is the most common malignancy in men, and until recently has been staged using standard imaging tests, such as ultrasound, CT, bone scan, and MRI. A novel imaging test targeting the membrane receptor, Prostate Specific Membrane Antigen (PSMA) using the PET tracer Ga-68 PSMA-11 has recently been approved in several countries for staging and assessing potential for radionuclide therapy. This agent was only recently approved in Canada, but has been available through the Health Canada Special Access (SA) Program for over a year, until it was approved (Illuccix, Telix Pharmaceuticals). Methods: In the past year, 275 prostate cancer patients were scanned at our facility (INITIO Medical Imaging, Burnaby BC) through Health Canada SA. All patients were required to have positive prostate cancer biopsies, with negative or indeterminate CT and bone scan, and rising PSA (prostate specific antigen) blood test in order to qualify for SA, or high risk Gleason Score prostate cancer. Results: Of the 275 patients, 71 had high risk cancers and 28/71 had positive PSMA studies (39%). 185 of the patients had biochemical evidence of recurrence and negative /indeterminate conventional imaging tests, and 101/185 or 55% had positive PSMA scans. All other patients were scanned for metastatic castrate resistant prostate cancer (MCRPC). Conclusions: Ga-68 PSMA scans are highly sensitive for upstaging patients at high risk of prostate cancer metastasis or recurrence, even with negative conventional imaging studies.

Ensuring access to innovative therapies for children, adolescents, and young adults across Canada: The single patient study experience.

Innovative therapeutic approaches are needed to alleviate the burden of life-limiting, rare, and chronic conditions affecting children, adolescents, and young adults (CAYA). This includes a need for improved access to both clinical research and to non-approved or off-label therapies, together with, ultimately, more therapies achieving regulatory approval in Canada. The single patient study (SPS), also known as an open label individual patient (OLIP) study, was introduced by Health Canada to open access to non-marketed drugs where a clinical trial is not readily available, but the drug is considered too investigational to be managed on a standard Special Access Program. SPS is designed for patients who have a serious or life-threatening condition and have exhausted available treatment options. Our report summarizes this relatively new development in the Canadian regulatory environment and highlights the opportunities and challenges as identified by regulators, pharmaceutical representatives, academic researchers, and patient/parent advocates.

High time? Psychedelics on cannabis-like fast track to legalization.

Alberta will soon become the first province to regulate psychedelic-assisted therapy. But, as with cannabis, momentum for medical access to psychedelics is outpacing research to guide their use. Earlier this year, Health Canada amended its Special Access Program to allow physicians to request

Treatment patterns and outcomes of second-line rituximab and thrombopoietin receptor agonists in adult immune thrombocytopenia: A Canadian retrospective cohort study

BackgroundThe optimal choice of second-line treatment for immune thrombocytopenia (ITP) is unclear. Guidelines recommend either rituximab, splenectomy, or thrombopoietin receptor agonists (TPO-RA). There is, however, scarce data comparing treatment patterns, outcomes and resource utilization across second-line treatments. Despite Canada's universal healthcare system, publicly funded access to second-line ITP therapies is highly variable across provinces/territories. ObjectivesTo describe treatment patterns and compare health service utilization and outcomes among recipients of second-line rituximab and TPO-RA for ITP. MethodsIn this multicentre retrospective cohort study, we included adults who received second-line ITP therapies rituximab, eltrombopag and romiplostim (2012-2020) in Alberta, Canada. Patients were identified through a provincially-funded special drug access (STEDT) program. We examined treatment patterns, predictors of second-line treatment, hospitalizations, blood product utilization, and outcomes. Kaplan-Meier survival curves were used to estimate the cumulative incidence of ITP-related hospitalizations (bleeding or infections), overall survival (OS) and relapse-free survival (RFS). Cox proportional hazards regression was used to examine the impact of second-line therapy on OS. Results223 patients received rituximab (67 %), eltrombopag (29 %), and romiplostim (4 %). TPO-RA recipients experienced significantly longer time from ITP diagnosis to second-line therapy compared with rituximab recipients (15.9 vs 6.7 months, P < 0.0001), accompanied by significantly higher platelet and IVIG utilization prior to second-line therapy. Age (adjusted odds ratio [aOR] 1.04, 95 % CI 1.02–1.07, P < 0.0001) and prior intracranial hemorrhage (aOR 12.7, 95 % CI 1.6–272.8, P = 0.03) were significant predictors of second-line TPO-RA. TPO-RA is associated with a trend towards longer median RFS (6.3 vs 3.8 years, P = 0.06) compared with rituximab, and similar rates of ITP-related hospitalizations, major bleeding, and thromboembolism. Age, time period, and Charlson comorbidity index, but not second-line ITP therapy, were significant predictors of OS. ConclusionsOur study identified older age and intracranial hemorrhage as predictors of second-line TPO-RA prescription in a real-world practice. There were no significant differences in hospitalizations and outcomes between second-line rituximab and TPO-RA, although delayed initiation of TPO-RA was associated with higher blood product utilization.

Surgical Considerations for an Osseointegrated Steady State Implant (OSIA2®) in Children.

Surgical Considerations for an Osseointegrated Steady State Implant (OSIA2®) in Children.

Navigating the complex realm of drug access in paediatric care.

A Drug Access Navigator (DAN) is a role that has been established in patient care settings with the goal of expediting the process by which patients obtain drugs through the Health Canada Special Access Program (SAP), individual drug companies' patient access programs (PAP), and public and private drug plans. In the paediatric setting, the process of accessing many drugs has grown increasingly complex. The majority of paediatric prescriptions involve 'off-label' drug use. This leads to an increased need for drug access through the SAP and/or PAPs and demonstrates that the need for a DAN may be particularly prominent in the paediatric population. To our knowledge, there is no evidence in the literature of a DAN functioning in a paediatric setting, though there is a demonstrable need. We plan to address this need by introducing a DAN for shared use at BC Children's Hospital, a paediatric tertiary care centre.

Targeting mutated isocitric dehydrogenase 1 (mIDH 1) in acute myeloid leukemia (AML): story of ivosidenib

In 2008, mutations in isocitric dehydrogenase 1 &amp; 2 (mIDH 1 &amp; 2) was first detected in glioblastoma multiforme (GBM) from among many types of solid tumour. Next year i.e. in 2009 acute myelogenous leukemia (AML) showed presence such mutation. mIDH 2 blocker enasidenib came into market for the first time for adult recurrent and relapsed AML in 2017. But mIDH 1 blocker ivosidenib (AG-120) is approved in 2019 in recurrent and relapsed AML. In the end 2019 it was approved for untreated adult AML. When it was in early phase trial it became eligible for special expanded access program as it showed encouraging results. Drug molecule's progress through preclinical and regulatory path is interesting. It is worthwhile to look into how it received market authorization while phase III trial was not over. Trial of both GBM and AML started in March 2014. Circumstances behind ivosidenib being first approved in adult recurrent and relapsed AML rather than in glioma where the mutation was first found are also discussed.

The Impact of Special Access Programs (SAP) on Prescribing Patterns in Metastatic Castration Resistant Prostate Cancer (mCRPC)

Background: Special access programs provide physicians in Canada access to new drugs before they are publicly funded, but little is known about how they impact prescribing practices. For men with metastatic castration-resistant prostate cancer post-docetaxel chemotherapy, a special access program for enzalutamide was open from June-December 2013. To better understand how this impacted prescribing practices, we surveyed medical oncologists at our institution. Methods: All four genitourinary medical oncologists at the Princess Margaret Cancer Centre completed an anonymous paper or electronic survey for each patient enrolled. The survey consisted of seven multiple-choice questions (with free text option) asking about disease characteristics, prior treatments, and reasons for prescribing enzalutamide. Results: Surveys were completed on all 155 patients; 92% (142/155) had metastatic disease, with 20% (28/142) having visceral disease; 8% (13/155) had non-metastatic disease; and the majority (92%) had progressive disease. All patients were on androgen deprivation therapy, 60% had prior prednisone, 30% had prior abiraterone, and 34% had prior docetaxel. Most (50%) used enzalutamide because it was supported by available data; 35% reported free drug was the motivating factor; 10% indicated their patients were unfit for chemotherapy; and in 5%, all other options were exhausted. Over half reported feeling enzalutamide was the appropriate treatment option for their patient at that time. Conclusions: During the special access program, most patients received enzalutamide in settings supported by available evidence. A minority did, however, received enzalutamide outside of the formally studied setting, suggesting that funding and accessibility can impact prescribing practices.

A Review of Black Widow (Araneae: Theridiidae) Envenomation, Epidemiology, and Antivenom Utilization in Canada.

Two species of black widow spider (BWS-Latrodectus hesperus Chamberlin & Ivie and Latrodectus variolus Walckenaer) naturally occur in Canada and are capable of causing deleterious envenomation to humans. No Canadian literature exists on the frequency of envenomations by these species or the use of antivenom in the treatment of those patients. A review of primary Canadian arachnology data was undertaken to identify BWS populations. A retrospective review of the Health Canada Special Access Program records generated epidemiology and the utilization of antivenom for BWS envenomations in Canada. The geographical distribution of BWS species is limited to along the southern Canadian border. From January 2009 to December 2015, there were five BWS envenomations that required treatment with antivenom and all cases occurred in British Columbia. An average patient age of 41 yr ± 21 SD (range 7-59) was observed, along with three of the five patients being female. The average number of vials used for treatment was 2 ± 1 SD (range 1-3). BWS Antivenin was also obtained by facilities in Alberta, Ontario, and Nova Scotia, but not used in any of these jurisdictions. Further investigation is necessary to determine the annual incidence of BWS envenomations and if treatment with BWS antivenin is required.

Stability of Methadone Hydrochloride for Injection in Saline Solution

Until October 2014, methadone hydrochloride for injection (10 mg/mL) was available in Canada through Health Canada's Special Access Programme. Diluted to 5 mg/mL in saline, it was used in pediatrics for acute and cancer-related pain. More recently, the department of pharmacy of the Centre hospitalier universitaire Sainte-Justine in Montréal, Quebec, proposed compounding a solution of methadone hydrochloride for injection (5 mg/mL) from bulk powder and saline solution for pediatric administration. To assess the stability of the proposed compounded preparation. Solutions of methadone hydrochloride in saline were prepared from bulk powder and stored in clear glass vials for up to 180 days at room temperature (25 °C) or with refrigeration (5 °C), with testing on days 0, 7, 14, 30, 60, 90, and 180. The appearance of the solutions and presence of particulate matter were assessed. A stability-indicating high-performance liquid chromatography (HPLC) method was developed to assay the concentration of methadone over time. No notable changes in appearance of the methadone solution were observed, particle counts did not exceed limits specified by the United States Pharmacopeia, and no microbial growth was observed. The HPLC analysis showed that the concentration of methadone remained above 90% on all study days. Methadone hydrochloride for injection prepared from bulk powder in saline solution at a concentration of 5 mg/mL remained chemically stable for at least 180 days when stored in clear glass vials at 5 °C and at 25 °C.

Targeting Mutated Isocitric Dehydrogenase 1 (mIDH 1) in Acute Myeloid Leukemia (AML): Story of Ivosidenib

In 2008, mutations in isocitric dehydrogenase 1 & 2 (mIDH 1 & 2) was first detected in glioblastoma multiforme (GBM) from among many types of solid tumour. Next year i.e. in 2009 acute myelogenous leukemia (AML) showed presence such mutation. mIDH 2 blocker enasidenib came into market for the first time for adult recurrent and relapsed AML in 2017. But mIDH 1 blocker ivosidenib (AG-120) is approved in 2019 in recurrent and relapsed AML. In the end 2019 it was approved for untreated adult AML. When it was in early phase trial it became eligible for special expanded access program as it showed encouraging results. Drug molecule's progress through preclinical and regulatory path is interesting. It is worthwhile to look into how it received market authorization while phase III trial was not over. Trial of both GBM and AML started in March 2014. Circumstances behind ivosidenib being first approved in adult recurrent and relapsed AML rather than in glioma where the mutation was first found are also discussed.

Real-world use of trifluridine/tipiracil for patients with metastatic colorectal cancer in Canada.

Outcomes for patients with metastatic colorectal cancer (mcrc) are improving with the introduction of new treatments. Treatment for patients who are still fit after failure of all available therapies represents a significant unmet need. In the present study, we analyzed real-world treatment patterns for patients enrolled in Health Canada's trifluridine/tipiracil (ftd/tpi) Special Access Program (sap) and Taiho Pharma Canada's Patient Support Program (psp). Demographic information and clinical treatment data were collected from adults with mcrc who were previously treated with, or were not candidates for, available therapies and who were enrolled in the sap and psp. For all patients, ftd/tpi treatment status, discontinuation reasons, and prior therapies were examined. The analysis included 717 Canadian patients enrolled in the ftd/tpi sap and psp from September 2017 to October 2018. In that cohort, 59.7% were men, median age was 65 years, and median duration of therapy was 77 days (25%-75% interquartile range: 43-106 days). Of treated patients, 67.1% maintained the same dose for the duration of therapy; 28.0% had a dose reduction.On multivariable analysis, duration of therapy was not influenced by sex, age, province, RAS mutation status, or prior therapies. However, prior oxaliplatin-based chemotherapy (capox or folfox) appeared to be associated with higher rates of discontinuation because of death or disease progression. In advanced mcrc, ftd/tpi is a well-tolerated therapy. The large number of patients enrolled in the access programs within a short period of time is reflective of major clinical need in this area, with many patients being eligible and interested in pursuing treatment in the refractory setting.

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