The list of "breakthrough" therapy designations continues to grow as FDA deems a second peanut allergy desensitization treatment worthy of the status, while Keeping Track also notes new submissions for autoimmune disease, acromegaly and migraine.

Two Approaches To Peanut Allergy Race To Phase III

FDA has granted its second "breakthrough" therapy designation for a peanut allergy treatment in three months, setting the stage for a race to Phase III for two desensitization strategies: Aimmune's oral AR101 and DBV Technologies SA's Viaskin Peanut transdermal patch. Both DBV and Aimmune (formerly known as Aimmune Therapeutics Inc.) hope to start pivotal trials by the end of 2015.

While the principle of allergen desensitization – exposing a patient to gradually increasing amounts of an allergen over time – is well accepted, its use for food allergens has been limited and ad hoc. Aimmune and DBV Technologies see significant commercial opportunity from a standardized, clinically tested regimen, with the added benefit of a well-defined target market of allergists that a small company could serve without a bigger partner.

Peanut allergies affect an estimated 1.5%-2% of the U.S. population. Aimmune calculates that 40%-50% of peanut allergic patients are sensitized to an exposure of 100 mg of peanut protein or less; a typical peanut kernel has 250-300 mg. Desensitization regimens aim to allow patients to tolerate an accidental exposure, and would not obviate the need for regular avoidance and emergency epinephrine pens.

Aimmune touts the "precise control" that its characterized oral desensitization immunotherapy (CODIT) platform brings to allergen desensitization. CODIT offers "accurately quantified dosages" of food protein – characterized peanut flour in AR101 – ranging from 0.5 mg to 300 mg. In the Phase II ARC001 study, patients followed a 20-week desensitization regimen. Up-dosing took place in the allergist office once every two weeks; daily dosing was at home.

Aimmune set its primary endpoint for Phase II at a 300 mg challenge dose, equivalent to a cumulative amount of peanut protein of 443 mg. All of the 23 patients in the AR101 arm tolerated that level of exposure on a double-blind, placebo-controlled food challenge, compared with five of 26 placebo patients.

Aimmune noted that the AR101 arm started out with 29 patients, but six discontinued early due to gastrointestinal adverse events and compliance issues.

DBV touts the safety of its epicutaneous immunotherapy (EPIT) approach. In the 221-patient Phase IIb VIPES study, the compliance rate for Viaskin Peanut was 97%, DBV said ([A#14150617001]). Analyses of the VIPES data and Aimmune's ARC001 Phase II study were presented at the European Academy of Allergy and Clinical Immunology Congress in early June. Aimmune announced the "breakthrough" designation June 18.

The antigenic protein delivered by the electrostatic patch is not absorbed systemically, DBV explained. Langerhans cells in the skin capture antigens and take them to the lymph nodes. VIPES found a low rate of drop-outs due to EPIT-related AEs – 0.9% – but more than 90% of subjects had local cutaneous reactions, mostly mild to moderate. VIPES met its primary endpoint, a responder rate based on patients reaching a reactive dose of 1,000 mg peanut protein or a reactive dose that is 10 times or more the initial reactive dose.

As DBV prepares for its Phase III PEPITES trial and Aimmune designs its pivotal study, the increased interaction with FDA provided for by the "breakthrough" designation could be very valuable. Neither sponsor has Phase III experience, and food allergy desensitization regimens have not yet been tested in pivotal clinical trials.

(See the 'Breakthrough Therapy' chart on the FDA Performance Tracker for detailed information on products receiving the designation.)

Novartis Seeks Two New Uses For Cosentyx

Novartis AG predicts FDA action in the second half of 2016 for two new indications for its anti-interleukin-17A monoclonal antibody Cosentyx (secukinumab): ankylosing spondylitis and psoriatic arthritis. That timeline exceeds the regular user fee timetable; Novartis completed the sBLA filings in the second quarter, which would put a 10-month standard review user fee goal for such submissions at April 2016 or earlier. The company explained that it is "very common" for "FDA to request additional data and/or analyses which may extend the approval timeline." The new indications are building blocks for the blockbuster status that analysts believe Cosentyx, the first IL-17 blocker approved, can achieve. Cosentyx launched in February into the very tightly controlled psoriasis market ([A#00150601003]).

Chiasma Submits First Oral Somatostatin Analog NDA

Chiasma Inc. announced the first NDA submission for an oral formulation of a somatostatin analog for treatment of acromegaly on June 15. The oral capsule formulation of octreotide, a peptide available for intramuscular injection generically and as Novartis AG's Sandostatin line, uses Chiasma's Transient Permeability Enhancer technology, which facilitates gastrointestinal absorption of unmodified drug. The company reported that 65% of Phase III patients taking twice-daily oral octreotide met the primary endpoint's responder classification based on circulating IGF-1 and growth hormone concentrations after seven months. The Chiasma product, which is in line for FDA action by April 2016, will also compete with Ipsen's subcutaneously injected somatostatin analog Somatuline Depot (lanreotide).

(See the User Fee Goals chart on the FDA Performance Tracker for information on pending applications.)

Avanir/OptiNose Intranasal Migraine Therapy Returns To FDA

The NDA for drug-device combo AVP-825 has been resubmitted to FDA and carries a Nov. 6, 2015 user fee goal, Avanir Pharmaceuticals Inc. disclosed June 17. The product, which delivers a low-dose (22 mg) powder formulation of the 5-HT1 agonist sumatriptan using OptiNose Inc.' Breath Powered intranasal delivery technology, is designed for fast-acting acute treatment of migraine. FDA issued a "complete response" letter in November 2014 asking for improvements to the device to address root causes of device use errors, supported by a new human factors validation study.

(See the Complete Response Letters chart on the FDA Performance Tracker for information on applications that have received action letters from FDA.)

Keeping Track: Dueling 'Breakthroughs' For Peanut Allergy

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