Top 5 Rare Disease News of the Week—September 23, 2018

#5: Hartmann Wellhoefer, MD, on Challenges Faced & Advances Made in Fight Against MPS

In a recent interview with Rare Disease Report^®, Hartmann Wellhoefer, MD, vice president of medical affairs, Rare Diseases and Internal Medicine, at Shire, discussed the biggest challenges faced and advances being made in the fight against mucopolysaccharidosis (MPS), a group of rare, hereditary, and incurable conditions for which only a handful of treatments are available.

Dr. Wellhoefer also highlights key takeaways from the 15th International Symposium on MPS and Related Diseases (ISMPS) which was held from August 2-4, 2018 in San Diego, California. Through the symposium, the MPS community was provided with an opportunity to learn more about the latest research being conducted in the field as well as share personal experiences to boost awareness and improve patient care.

Rare Disease Report ^®: You recently attended the 2018 International Symposium on Mucopolysaccharidosis (MPS) and Related Diseases. Can you tell me about this conference?

Dr. Wellhoefer: The ISMPS is one of the most unique congresses I’ve ever attended because of the presence of patient advocacy groups, patients, their families, and caregivers, as well as physicians and industry representatives. You actually hear children chatting and laughing in the hallways of the Congress, and more importantly, in the scientific sessions. It is these sounds that remind you it is all about the patient. This mix gives the event a very different atmosphere—almost a lightness, despite the fact that we’re talking about very serious and often life-threatening diseases.

At this Congress, there is also a tangible sense of hunger for new information. You walk the hallways and you see a global medical expert speaking with a patient and/or caregiver, having earnest conversations about MPS and sharing their perspectives.

The experience of attending and participating in this conference reinforces some of the major challenges of working in rare diseases, like MPS. Each of the MPS diseases—7 in total—are all very different in terms of the onset and type of symptoms. At ISMPS, because of the patient presence, you are able to see the individuality in each patient—or, to put it in medical terminology—the different phenotypes within each of the MPS diseases. This high level of variability within the same disease is the very challenge we have across almost all of the 7,000 or so rare diseases, some of which have treatments, most of which do not. This reminds us that there is much work to be done and that we have our work cut out for us—as an industry, and as a leader in rare diseases.

#4: Children with Acute Lymphoblastic Leukemia May Be Immunologically Disparate at Birth

Read the full interview with Hartmann Wellhoefer, MD, on challenges faced and advances made in the fight against MPS.Investigators in Denmark have found new evidence suggesting that children who develop acute lymphoblastic leukemia may be predisposed from birth, and their immune responses to early childhood infections may offer clues to how the disease develops.

Childhood acute lymphloblastic leukemia (ALL) is a cancer of the blood and bone marrow originating in the T and B lymphoblasts in the bone marrow. In children with ALL, the bone marrow makes too many immature lymphocytes, and the immune system weakens. With a decrease in healthy red blood cells, white blood cells, and platelets, children can experience infections and anemia and may bleed easily. According to the National Cancer Institute, rates of childhood ALL have been on the rise along with other childhood cancers since 1975. It is the most commonly diagnosed cancer in children, making up about 25% of all cancer diagnoses in children under the age of 15 years.

With remission rates of about 98% and a 90% survival rate at 5 years, children with ALL today benefit from advances in treatment. Many symtpoms of ALL are similar to other conditions and can include aches in the arms and legs, unexplained bruising, enlarged lymph nodes, unexplained fever, tiredness, unexplained weight loss, and prolonged bleeding from minor injuries. Risk factors for children developing ALL include prenatal exposure to x-rays, post-natal exposure to high levels of radiation, chemotherapy treatment, inherited genetic variants, and genetic conditions including Down syndrome.

In a new study published in the journal Cancer Research, a research team led by scientists at the Statens Serum Institut in Copenhagen, Denmark, explored the hypothesis that children with ALL are born with a dysregulated immune function that together with postnatal environmental exposures causes the development of the disease in childhood. Previous studies had indicated that children could develop ALL due to an overreaction to childhood infections.

#3: Positive Preliminary Phase 2 Data Reported for DLBCL Combination Therapy

Read more about how children with acute lymphoblastic leukemia may be immunologically disparate at birth. IMV Inc. recently announced positive preliminary data collected from its phase 2 clinical trial evaluating a combination therapy consisting of anti-cancer immunotherapy, DPX-Survivac, in combination with low dose cyclophosphamide and Merck’s pembrolizumab (Keytruda) for the treatment of diffuse large B-cell lymphoma (DLBCL). The therapy was found to have an acceptable safety profile, with patients showing tumor regression and/or stable disease.

“This type of lymphoma remains a significant unmet medical need in today’s treatment landscape,” Frederic Ors, BSc, MSc, chief executive officer of IMV Inc., told Rare Disease Report^®. “There is a poor prognosis for DLBCL patients who are not cured by first-line chemotherapy, and there is an increasing incidence of the disease in elderly patients who often cannot tolerate the current standard-of-care.”

Investigators anticipate enrolling 25 participants whose DLBCL expresses survivin—a tumor antigen expressed in more than half of patients with the cancer—in the phase 2, interventional, open-label, single group assignment trial. Data pertaining to the first 4 evaluable participants were included in the announcement.

“DLBCL has an overexpression of the survivin protein—in approximately 60% of patients, I believe,” Ors explained. “DPX-Survivac’s mechanism of action targets survivin and elicits a cytotoxic T cell immune response against cells presenting survivin peptides. Survivin, recognized by the National Cancer Institute (NCI) as a promising tumor-associated antigen, is broadly over-expressed in many cancer types, and plays an essential role in antagonizing cell death, supporting tumor-associated angiogenesis, and promoting resistance to anti-cancer therapies.”

#2: Myeloproliferative Neoplasms Impair Patient Employment Status & Work Productivity

Read more about the positive preliminary phase 2 data reported for the potential DLBCL combination therapy. While a pronounced symptom burden is not remarkable for patients with myeloproliferative neoplasms (MPNs), a recent study investigating the impact of MPNs on employment status, career potential, and work productivity is since few studies have investigated the rare blood cancers’ effects on patients’ professional lives.

In a recent study published in BMC Cancer, investigators found patients with MPNs experience changes in employment status and meaningful impairments on work productivity and activities of daily living, with the degree of impairment reflecting the severity of symptom burden.

For their research, the investigators recruited US respondents aged 18 to 70 years of age who have been diagnosed with MPNs, including myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET) to participate in their cross-sectional Living with MPNs survey. The survey included 100 questions related to MPN diagnosis, disease-related medical history, MPN-related symptoms and functional status, changes in employment and work productivity, and impact on daily activities since diagnosis.

Symptom burden was assessed by The MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS), while the effects of MPNs on work productivity and activity (7-day recall) among currently employed respondents was assessed by The Work Productivity and Activity Impairment Specific Health Problem questionnaire (WPAI-SHP). Spearman’s coefficients were used to calculate correlations between MPN-SAF TSS and WPAI-SHP scores.

#1: Robert J. Kreitman, MD, on New Kind of Treatment for Hairy Cell Leukemia

Read more about how myeloproliferative neoplasms impair patient employment status and work productivity.This month, the US Food and Drug Administration (FDA) approved the first new treatment option for hairy cell leukemia (HCL) in over 20 years—AstraZeneca’s moxetumomab pasudotox (Lumoxiti), a new kind of treatment developed to fulfill an unmet need for patients with the rare blood cancer whose disease has progressed after trying other approved therapies.

In an exclusive interview with Rare Disease Report^® (RDR^®), Robert J. Kreitman, MD, lead investigator on the drug’s phase 3 clinical trial, provided insight on what makes the CD22-directed cytotoxin so unique as well as the clinical implications of its approval.

RDR^®: Can you discuss Lumoxiti? What makes the treatment unique?

Dr. Kreitman: It’s an idea that goes back several decades—taking an antibody or part of an antibody and partnering it with a toxin so that the antibody will bind to a target on the cancer cell, go inside, and then the toxin [will] kill the cell. In Lumoxiti, the toxin comes from Pseudomonas aeruginosa bacteria—it’s a very powerful toxin.

Can you discuss the phase 3 trial of Lumoxiti?

We had a preliminary meeting with the FDA back in 2012 where we planned out what we needed to achieve in order to have the drug approved. We knew back then that it had good activity, but we received good feedback from the FDA about what kind of trial would be acceptable to design.

We designed a trial where everyone who entered into the trial would receive Lumoxiti at a fixed dosing level. We decided we would observe the treated patients for toxicity and efficacy, and if they achieved a certain complete remission rate that was durable enough. In other words, we observed whether the patient had improved blood counts for at least 6 months—that counted towards what we called the primary endpoint.

We met the primary endpoint, and the FDA, therefore, approved the drug.

Read the full interview with Robert J. Kreitman, MD, on new HCL treatment, moxetumomab pasudotox (Lumoxiti).