Projected blockbuster bio products with potential launches in 2016

Dupilumab, Regeneron/Sanofi

Dupilumab is the first systemic therapy to demonstrate positive Phase III results in patients with moderate-to-severe atopic dermatitis. The serious, chronic inflammatory skin disease is marked by widespread rash, itching and associated psychosocial comorbidities.

Dupilumab inhibits interleukin-4 and interleukin-13, which are small anti-inflammatory proteins secreted by cells that are thought to play a role in eczema.

Regeneron Pharmaceuticals and Sanofi announced in early April 2016 that two placebo-controlled Phase III trials evaluating investigational dupilumab in adult patients with inadequately controlled moderate-to- severe atopic dermatitis met their primary endpoints. In the trials, known as LIBERTY AD SOLO 1 and SOLO 2, treatment with dupilumab as monotherapy significantly improved measures of overall disease severity, skin clearing, itching, quality of life, as well as mental health.

The first in a new class of immunotherapies, FDA granted dupilumab breakthrough therapy designation in atopic dermatitis in November 2014. A U.S. filing for the biologic agent is on track for third-quarter 2016.

Empliciti (elotuzumab), Bristol-Myers Squibb

Empliciti gained U.S. regulatory approval in November 2015 in combination with two other therapies to treat people with multiple myeloma who have received one to three prior medications. A type of blood cancer that occurs in infection-fighting plasma cells, multiple myeloma may result in a weakened immune system and cause other bone and kidney problems.

Empliciti activates the body’s immune system to attack and eliminate multiple myeloma cells. The drug is approved in combination with the marketed multiple myeloma medicine Revlimid (lenalidomide) and dexamethasone (a type of corticosteroid).

The immunostimulatory antibody specifically targets signaling lymphocyte activation molecule family member 7 (SLAMF7), a cell-surface glycoprotein. With a dual mechanism-of-action, Empliciti directly activates the immune system through natural killer cells via the SLAMF7 pathway. The drug additionally targets SLAMF7 on myeloma cells, tagging these malignant cells for natural killer cell-mediated destruction by way of antibody-dependent cellular toxicity.
Bristol-Myers Squibb and AbbVie are co-developing Empliciti, with Bristol-Myers Squibb solely responsible for marketing activities.

Taltz (ixekizumab), Eli Lilly

The immunology drug Taltz during March 2016 received FDA clearance for treating psoriasis. In Phase III studies, 87–90 percent of patients treated with ixekizumab experienced at least a 75 percent improvement in their skin clearance at 12 weeks, and 35–40 percent saw 100 percent clearance at week 12.

Taltz injection 80 mg/mL was introduced in the United States in early May 2016 for treating moderate-to-severe plaque psoriasis in adult patients who are candidates for systematic therapy or phototherapy. Lilly anticipates additional regulatory approvals for ixekizumab during 2016: for psoriasis in Europe as well as for psoriasis and psoriatic arthritis in Japan.

The new product is designed to specifically target IL-17A, a protein that plays a role in driving underlying inflammation in psoriasis. The humanized IgG4 monoclonal antibody selectively binds with interleukin 17A cytokine and inhibits its interaction with the IL-17 receptor. The naturally occurring cytokine IL-17A is involved in normal inflammatory and immune responses. Taltz inhibits the release of pro-inflammatory cytokines as well as chemokines.

Ocrelizumab, Roche

The investigational, humanized monoclonal antibody ocrelizumab is designed to selectively target CD20-positive B cells. Those are a specific type of immune cell believed to be a key contributor to myelin (nerve cell insulation and support) and axonal (nerve cell) damage, which can lead to disability in people with multiple sclerosis. Based on preclinical studies, ocrelizumab binds to CD20 cell surface proteins expressed on certain B cells, but not on stem cells or plasma cells, and therefore significant functions of the immune system may be preserved.

The Phase III clinical development program for ocrelizumab (ORCHESTRA) includes three trials: OPERA I, OPERA II, and ORATORIO. OPERA I and OPERA II are identical Phase III, randomized, double-blind, double-dummy, global multi-center trials that evaluated the efficacy and safety of ocrelizumab (600 mg administered by intravenous infusion every six months) versus interferon beta-1a (44 mcg administered by subcutaneous injection three times per week) in 1,656 people with relapsing forms of MS (i.e., relapsing-remitting MS and secondary-progressive MS with relapses). ORATORIO is a Phase III, randomized, double-blind, worldwide multi-center trial that evaluated the efficacy and safety of ocrelizumab (600 mg administered by intravenous infusion every six months; given as two 300 mg infusions two weeks apart) compared with placebo in 732 people with primary progressive multiple sclerosis (PPMS).

The U.S. Food and Drug Administration during February 2016 granted breakthrough therapy designation to ocrelizumab for treating people with PPMS. Ocrelizumab is the first investigational medicine to receive breakthrough therapy designation for multiple sclerosis.

Roche intends to pursue marketing approval for PPMS and relapsing multiple sclerosis (RMS), a more common type of the disease. The company was anticipating submitting data from the three pivotal Phase III trials to worldwide regulatory authorities during first-half 2016.

Tecentriq (atezolizumab), Genentech

The monoclonal antibody atezolizumab is designed to bind with a protein called PD-L1. By binding to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, atezolizumab blocks its interactions with PD-1 and B7.1 receptors. By inhibiting PD-L1, atezolizumab may allow for the activation of T cells. The new drug may additionally affect normal cells.

During May 2016, Tecentriq gained U.S. regulatory clearance as the first FDA-approved treatment for people with a specific type of bladder cancer in more than 30 years. Tecentriq is also the first anti-PDL1 cancer immunotherapy to be approved by the FDA. Accelerated approval was granted for treating people with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-based chemotherapy, or whose disease has worsened within 12 months of receiving platinum-based chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant). Urothelial carcinoma accounts for nine-tenths of all bladder cancers and can be found in the renal pelvis, ureter, and urethra.

Genentech is additionally studying Tecentriq in a confirmatory Phase III trial (IMvigor 211) comparing the drug to chemotherapy in people whose bladder cancer has progressed on at least one prior platinum-containing regimen.

Uptravi (selexipag), Actelion

Gaining FDA approval at the end of 2015, Uptravi was given the green light for treating pulmonary arterial hypertension (PAH, WHO Group 1) to delay disease progression and reduce the risk of hospitalization for PAH. The potent, oral, selective IP prostacyclin receptor agonist was initially discovered and synthesized by Nippon Shinyaku.

Uptravi and its major metabolite selectively target the prostacyclin receptor (additionally known as IP receptor). The IP receptor is one of five major kinds of prostanoid receptor (IP, EP, DP, TP, FP). Prostacyclin activates the IP receptor to induce vasodilation as well as inhibit proliferation of vascular smooth muscle cells.

Uptravi was launched in the United States during January 2016. As of May 2016, marketing approval also had been received in Canada, New Zealand, Australia, South Korea, and the European Union. Regulatory reviews under way include Japan, Switzerland, Taiwan, and Turkey.