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New Medicines

Palforzia Severe peanut allergy in children and adolescents ages 4 to 17 years

Information

Palforzia
New molecular entity
Aimmune Therapeutics
Nestle Health Science

Development and Regulatory status

Approved (Licensed)
Approved (Licensed)
Launched
Dec 20Nestle plans for UK launch in May 21 [25]
Dec 20Approved in EU and UK [24].
Oct 20Recommended for EU approval by CHMP - the full indication is "for the treatment of patients aged 4 to 17 years with a confirmed diagnosis of peanut allergy. Palforzia may be continued in patients 18 years of age and older." It should be used in conjunction with a peanut-avoidant diet. This medicine should be administered under the supervision of a healthcare professional qualified in the diagnosis and treatment of allergic diseases. [22]
Mar 20Launched in US [20].
Feb 20Analysts predict this will be one of the top 10 most-anticipated new US drug launches of 2020 based on estimated global sales in 2024 [19].
Jan 20The FDA has approved Palforzia for treatment of peanut allergy in 4-17 year olds indicated for the mitigation of allergic reactions, including anaphylaxis [18]
Sep 19Aimmune restated plans to submit an MAA for AR101 to the EMA in mid-2019. Its BLA to the US FDA has a target action date of late January 2020 [11].
Jun 19Filed in EU to to reduce the frequency and severity of allergic reactions following exposure to peanuts in children and adolescents ages 4 to 17 [14].
Mar 19AR101 was filed in the US in Dec 18 [13].
Mar 19A new market research report identifies AR101 as one of seven new drugs it believes will hit sales of $1 billion or more, the so-called “blockbuster” mark, by 2023 [12].
Jan 19Aimmune Therapeutics intends to file in EU in the first half of 2019, for the treatment of peanut-allergic in children, adolescents, and adults. It will include data from the PALISADE, ARC004, RAMSES and ARTEMIS trials [10].
Oct 15EMA approves a Paediatric Investigation Plan (PIP) for AR101 for treatment of peanut allergy [3].
Jun 15US FDA grants Breakthrough Therapy Designation status to AR101 for oral treatment of children and adolescents (4 - 17 years) with peanut hypersensitivity. AR101 has been granted Fast Track designation by the US FDA [3].

Category

An oral immunotherapy (OIT) containing pharmaceutical-grade formulated peanut protein in a flour formulation. With OIT, a very small amount of an allergen (insufficient to cause a reaction) is administered in a gradual, controlled updosing manner.
Food allergy is thought to affect 5 in 100 young children and 3-4 in 100 adults in westernised countries [1].
Severe peanut allergy in children and adolescents ages 4 to 17 years
Oral

Further information

Yes

Trial or other data

Oct 20Nestlé completes acquisition of Aimmune Therapeutics [23].
Jul 20ARTEMIS RCT (n=175) found that more children with peanut allergy given AR101 oral immunotherapy tolerated a food challenge (1000 mg peanut protein) than those given placebo (58% vs 2%, p<0.0001). Adverse event rates were similar [21].
Jul 20ARTEMIS RCT (n=175) found that more children with peanut allergy given AR101 oral immunotherapy tolerated a food challenge (1000 mg peanut protein) than those given placebo (58% vs 2%, p<0.0001). Adverse event rates were similar [21].
Nov 19Nov 19: Additional analysis from the PIII PALISADE and PIII ARTEMIS trials have been released. Pooled results from both studies found that the median tolerated dose of peanut protein increased from 10mg to 1000mg between entry and exit food challenges, about two thirds of patients tolerated 600mg and more than half tolerated 1000mg of peanut protein. In PALISADE approximately 14% patients required administration of adrenaline to treat TEAEs; in ARTEMIS 6.8% patients required administration of adrenaline. The authors report that the difference in proportions administered adrenaline may be indicative of different practices in Europe and the USA [16,17].
Jun 19Results from open-label extension study of the PIII PALISADE trial (the ARC004 study) shows the potential benefits of continued daily AR101 dosing after 1 year. An extension of daily therapy with AR101 by 28 weeks led to improved tolerability with lower numbers of adverse events compared to the PALISADE therapeutic dosing period. Initial PIII data showed AR101 was effective in >67% of children/ adolescents. The study showed that 80% of pts who continued taking AR101 could tolerate doses of at least 1000mg of peanut protein. Nearly half tolerated a dose of 2000mg during the exit food challenge [13].
Mar 19Positive topline data announced from PIII ARTEMIS trial (n=175 children aged 4-17) in Europe. The children went through about 6 months of dose escalation and then 3 months of a daily therapeutic dose of AR101 300 mg or placebo followed by an exit double-blind, placebo-controlled food challenge. The trial met its primary efficacy endpoint which was pts ability to tolerate a 1000-mg single dose of peanut protein (equivalent of ~3-4 peanut kernels). The median tolerated dose of peanut protein for pts receiving AR101 improved 100-fold, from 10 mg at baseline to 1,000 mg at exit. No cases of anaphylaxis or of eosinophilic esophagitis (EoE) were observed [11].
Nov 18The PIII PALISADE trial enrolled 496 children aged 4 to 17 years of age with peanut allergy; the results show that treatment with AR101 (12% defatted peanut flour) resulted in more subjects able to ingest 600 mg or more of peanut protein, without dose-limiting symptoms vs placebo (67.2% vs 4.0%; P<0.001) [9].
Oct 18AR101 contains the complete range of natural peanut proteins, which are combined with pharmaceutical-grade ingredients to ensure that each dose has consistent amounts of peanut protein with well-defined concentrations of peanut allergens, especially the three key allergenic proteins (Ara h1, h2 and h6). Patients ingest AR101 mixed into small amounts of palatable, age-appropriate food. AR101 is part of Aimmune approach to treating food allergies using its CODIT™ (characterized oral desensitization immunotherapy) system. The CODIT system is based on extensive independent scientific research on oral immunotherapy demonstrating that food allergy patients can be desensitised to food allergens by being administered well-defined, gradually increasing doses of the allergen over a period of months [2].
Feb 18PIII PALISADE study (n=499) eports 67.2% of those receiving AR101 vs 4% of those on placebo were able to tolerate exposure of at least a 600-mg dose of peanut protein. A Biologics License Application is to be submitted to the US FDA by the end of 2018 [8].
Oct 17Aimmune Therapeutics will collaborate with Sanofi/Regeneron to trial AR101 with adjunctive dupilumab in peanut-allergic pts. The planned PII trial is expected to begin in 2018. It will explore desensitisation with AR101 treatment with adjunctive dupilumab (or placebo) in peanut-allergic pts, with a proposed primary endpoint of tolerating a certain dose of peanut protein in a double-blind, placebo-controlled food challenge (DBPCFC) that will include dose matching and exceeding those being tested in current AR101 studies. The study also includes a proposed exploration of sustained unresponsiveness (when peanut-allergic pts can tolerate a defined amount of peanut protein with only mild allergic symptoms) after discontinuation of therapy in another DBPCFC [7].
May 17RAMSES (ARC007, NCT03126227) is a randomized, double-blind, placebo-controlled trial enrolling approximately 440 peanut-allergic patients aged 4–17 in US and Canada. The trial will monitor treatment-emergent adverse events during a six-month up-dosing period, and then, after unblinding, follow patients for at least six months on the maintenance dose of 300 mg of AR101 per day[6].
Dec 16NCT02993107 is a PIII follow-on from the PALISADE study due to start Dec 16 and complete Dec 20 after recruiting 500 subjects and following them for 38 months [5].
Mar 16PIII PALISADE trial is expected to complete collection of primary outcome data in Nov 17 [4].
Mar 16Aimmune Therapeutics announce data from the open-label ARC002 PII trial. All patients who completed 12 weeks of low-dose maintenance therapy were desensitized to levels of peanut protein beyond the 250-300 mg typically found in one peanut kernel. In ARC002, 40 patients completed 12 weeks of post–up-dosing maintenance therapy at a daily dose of 300 mg of AR101. Those patients were then administered a double-blind, placebo-controlled food challenge (DBPCFC), in which 100 percent, 90 percent, and 60 percent tolerated cumulative amounts of peanut protein of 443 mg, 1,043 mg, and 2,043 mg, respectively (corresponding to 85 percent, 77 percent, and 51 percent on an intent-to-treat basis). Patients who passed the highest challenge level demonstrated protection against a challenge equivalent to seven or eight peanuts [2].
Mar 16Aimmune has previously released positive data from the PII ARC001 study (NCT01987817) in 55 patients aged 4-21 years with a clinical history of allergy to peanuts or peanut-containing foods. The primary endpoint of the proportion of patients achieving desensitisation to cumulative amounts of peanut protein of 443mg and 1 043mg at 6 - 9 months, was met. Patients followed a slow, steady up-dosing regimen to at least 20 times (and up to 200 times) the amount of peanut protein that would originally have caused a reaction [3].
Dec 15Aimmune Therapeutics initiates the PIII PALISADE trial of AR 101 for desensitisation of children and adults with peanut hypersensitivity (ARC003; NCT02635776). The randomised, double-blind, placebo-controlled trial intends to enrol approximately 500 children, adolescents and adults aged 4 to 55 years in the US and is expected to expand to Canada and some European countries. The company expects to complete the enrolment in the study H2 2016 and complete the trial in the H2 2017. The study will be followed by an expansion phase, which will include one year old allergic patients [3].

Evidence based evaluations

Palforzia Peanut allergy in children aged 1 to 3 years

Information

Palforzia
Licence extension / variation
Aimmune Therapeutics
Nestle Health Science

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Oral immunotherapy (OIT) containing peanut protein. With OIT, a very small amount of an allergen (insufficient to cause a reaction) is gradually up-titrated (followed by ongoing daily maintenance) until de-sensitisation to a certain amount of the allergen
UK prevalence of peanut allergy in children varies from 200 to 1,900 per 100,000 [1]. In 2004, 250,000 children in England had a peanut allergy [2]. The number of people with peanut allergy is increasing but about 20% of children outgrow their allergy [1,3].
Peanut allergy in children aged 1 to 3 years
Oral

Viaskin Peanut Severe IgE-mediated peanut allergy in children aged 4 to 11 years

Information

Viaskin Peanut
New formulation
DBV Technologies
DBV Technologies

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Not approved
Nov 20DBV Technologies announces filing and validation of MAA for Viaskin Peanut by EMA [22].
Aug 20FDA have not approved Viaskin patch. In the FDA´s complete response letter, the FDA say that the patch’s design would need to be modified, with a focus on site adhesion and how that affects the treatment’s efficacy. The company will need to conduct a new human factor study and deliver supplementary clinical data and manufacturing information. No safety concerns were raised. The company will collaborate with the FDA to resolve these issues and plan to scale down other programs aimed at using the Viaskin patch for milk and egg allergies in children.[21]
Mar 20FDA has identified questions regarding efficacy, including the impact of patch-site adhesion. Therefore, the Allergenic Products Advisory Committee (APAC) meeting to discuss the BLA will no longer take place as previously scheduled on May 15, 2020. DBV is in communication with the FDA about submitting additional information on patch-site adhesion from its clinical program as well as long-term efficacy results from the three-year open-label extension study, PEOPLE, to answer FDA’s questions. As far as DBV knows, the target action date of August 5, 2020 remains unchanged. However, submission of additional information to the FDA may constitute a major amendment to the BLA and could extend the target action date [20].
Oct 19FDA annouced acceptance of DBV’s Biologics License Application for Viaskin Peanut immunotherapy for treatment of peanut-allergic children ages 4 to 11 years with a target action date of Aug 2020.[18]
Feb 19DBV Technologies announces intention to re-submit Biologics License Application to the US FDA for Peanut hypersensitivity in children 4 to 11 years of age in third quarter of 2019 [17].
Dec 18The Biologics License Application was withdrawn based on verbal and written correspondence which stated lack of sufficient details regarding manufacturing procedures and quality controls. Following the feedback from the US FDA, the company intends to resubmit the application for Viaskin Peanut as soon as possible [16]
Oct 18Filed for Peanut hypersensitivity in children 4 to 11 years of age in the USA [13]
Oct 17Viaskin Peanut has been granted fast track designation by the FDA as well as breakthrough status. [9,10]
Jun 15EMA issues positive opinion on the paediatric investigation plan for Viaskin for treatment of children with peanut allergy [4].
Apr 15The FDA has awarded a breakthrough status for Viaskin Patch treatment for peanut allergies following positive Phase IIb results. [1]

Category

Epicutaneous immunotherapy (EPIT) containing peanut protein. EPIT maintains allergen on the skin for prolonged periods to achieve desensitisation.
UK prevalence of peanut allergy varies from 200 to 1,900 per 100,000 children [19]. Number affected is increasing but about 20% of children outgrow their allergy [19].
Severe IgE-mediated peanut allergy in children aged 4 to 11 years
Transdermal

Further information

Yes

Trial or other data

Jan 20Positive long-term data announced from PIII PEPITES trial - ater 3 years, 85.9% of children increased their eliciting dose (ED) from baseline. And about 51.8% hit an ED of at least 1,000 mg peanut protein by the 3rd year.[19]
Jun 19PIII PEOPLE trial (NCT03013517) is a follow up study that enrolled 300 children who completed PEPTIDES study. After children completed the 12 month placebo-controlled period in PEPITES, they were eligible to enrol to receive up to 36 months of peanut allergy immunotherapy 250µg . The PEPITES study is due to complete February 2020 [15].
Feb 19PIII PEPITES trial (n=356) is published. The authors reported a statistically significant difference in treatment response rate after 12 months of treatment with peanut-patch therapy, vs placebo, (35.3% vs 13.6%), but did not meet a pre-specified criterion for a positive trial result [14].
Nov 18PIII trial (PEPITES) results announced. Patients were randomized 2:1 to receive either Viaskin Peanut 250 mcg or placebo for 12 months. 62.6% of patients who were treated for 12 months in the PEPITES trial increased their peanut Eliciting Dose (ED), compared to 28.0% of patients in the placebo group, Odds Ratio 4.3 (95% CI 2.7- 7.0), p<0.001 [12].
Oct 18NHSE commissions services (including procedures and treatments) for patients with complex drug allergy – investigation including drug challenges, and desensitisation (antibiotics, analgesics (NSAID/aspirin/opiates), anaesthetics, contrast media, biologics) - but not food [PSS Manual 2013/14]. A number of similar products are in development for peanut and other food allergies. The aim is not necessarily to enable unrestricted consumption of the food involved, but to reduce sensitivity thresholds so that affected individuals are at lower risk of suffering clinically significant reactions to contact with small amounts of the allergen in day to day life. If effective, such products could not only reduce mortality and morbidity, but would markedly improve quality of life for affected individuals.
Nov 17Positive topline results from PIII REALISE (N=400) trial announced. The double-blinded period compared safety of Viaskin Peanut 250 µg vs. placebo for 6 months. The trial met its primary objective, demonstrating that Viaskin Peanut was well-tolerated with no new or unexpected adverse events. In the blinded period, the discontinuation rate was 2.5%, with a 1.0% dropout related to adverse events. Mean patient compliance was above 95%. Only 3 serious adverse events in 3 pts occured and only in the Viaskin Peanut arm which was a case of moderate anaphylaxis that responded to standard outpatient therapy. Local application site reactions were more common but only of mild to moderate severity. This was the only PII trial to study Viaskin Peanut in the absence of food challenges which reflects a real-life setting.[11]
Oct 17DBV announced topline data from the PEPITES (NCT02916446) PIII trial;35.3% of pts responded to Viaskin Peanut 250 μg after 12months vs. 13.6% of pts on placebo (difference in response rates = 21.7%; p=0.00001; 95% CI = 12.4% -29.8%). Safety and tolerability were similar between grps; serious adverse events (SAEs) were noted in 12 cases in 10 pts in the active arm (4.2%), and 6 cases in 6 pts in the placebo arm (5.1%). The primary endpoint did not reach the 15% lower bound of the CI that was proposed in the statistical analysis plan submitted to the US FDA. However, DBV will continue discussions with the FDA and await data from the REALISE study.[9,10]
Mar 17the company has announced that due to greater than expected patient demand, enrolment into the REALISE study (NCT02916446) has completed with a higher number of patients randomised than expected (n=394 vs. 335). Topline results from this and the PEPITES study are expected in the second half of 2017 [8]
Dec 16NCT02916446 (REALISE) is a PIII 3-year safety study in 335 children; enrolment started in Oct 16 and the study is due to complete Sep 20 with collection of primary data by Sep17 [7].
Oct 16DBV Technologies announces data from a two-year follow-up to a PIIb trial. Response rates remain above 80% among children who have received three years of treatment with the 250-μg formulation, and median compliance across the study continues at around 96%. When the Phase IIb trial ended, DBV enrolled 21 of the 28 children who received the 250-μg Viaskin Peanut formulation during the study into a follow-up program. After losing one patient to follow-up during the first stage of the extension, DBV closed out the first year of the study with a response rate of 80% among this group. In the second year, DBV lost track of another three patients and emerged with a response rate of 83%. The mean and median cumulative reactive dose (CRD) of peanut protein, respectively, rose and stayed constant over the course of the second year. DBV also reported the maintenance of peanut-specific immunoglobulin E levels and continued high levels of immunoglobulin G4, although it has yet to provide numbers on either. DBV also looked at what happens when patients who have become unresponsive to a CRD of 1,440 mg or more of peanut protein stop taking Viaskin Peanut. The top-line finding is that all 19 of the children were still unresponsive to a CRD of 1,440 mg two months after stopping treatment, suggesting the response to the drug may be durable [6].
Dec 15NCT02636699 (PEPITES) is a double-blind, placebo-controlled, randomized PIII pivotal trial to assess the efficacy and safety of peanut epicutaneous immunotherapy with viaskin peanut in 330 peanut-allergic children (aged 4-11 years). The combined primary endpoint is based on a responder analysis after 12 months of treatment with Viaskin Peanut 250mcg. For patients with a baseline peanut protein eliciting dose (ED) ≤ 10mg, a responder is defined as a patient with a peanut protein ED ≥ 300mg peanut protein; for subjects with a baseline ED >10mg, a responder will be defined as a patient with a peanut protein eliciting dose ≤1,000 mg of peanut protein. The study starts in Dec 15 and is due to complete Jul 17 [5].
Apr 15The primary endpoint was met in the phase IIb VIPES trial, in July 2014, to investigate the efficacy and safety of Viaskin® Peanut immunotherapy in patients with a history of immediate hypersensitive reaction to peanut (NCT01675882). Results showed 250 micrograms of Viaskin Peanut significantly (statistically different) positively impacted peanut allergies in children; 50% of patients responded positively to the patch, compared to 25% of those who received a placebo. Overall, Viaskin Peanut 250 micrograms showed better results than Viaskin Peanut 100 micrograms or 50 micrograms. [1,3]

Evidence based evaluations

Viaskin PeanutSevere IgE-mediated peanut allergy in children aged 1 to 3 years

Information

Viaskin Peanut
Licence extension / variation
DBV Technologies
DBV Technologies

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials

Category

Epicutaneous immunotherapy (EPIT) containing peanut protein. EPIT maintains allergen on the skin for prolonged periods to achieve desensitisation.
UK prevalence of peanut allergy varies from 200 to 1,900 per 100,000 children [4]. Number affected is increasing but about 20% of children outgrow their allergy [4].
Severe IgE-mediated peanut allergy in children aged 1 to 3 years
Transdermal

Further information

Yes