Date: 2015-02-02
Type of information: Development agreement
Compound: TD-4208 (biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester)
Company: Mylan (USA - PA) Theravance (USA - CA)
Therapeutic area: Inflammatory diseases - Respiratory diseases
Type agreement: development commercialisation
Action mechanism: long-acting muscarinic antagonist.TD-4208 (biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester) is an investigational long-acting muscarinic antagonist (LAMA) in development for the treatment of chronic obstructive pulmonary disease (COPD).
Disease: chronic obstructive pulmonary disease (COPD) and other respiratory diseases
Details: * On February 2, 2015, Theravance Biopharma and Mylan announced that the two companies will partner on the development and, subject to FDA approval, commercialization of TD-4208, a novel investigational once-daily nebulized long-acting muscarinic antagonist (LAMA) for chronic obstructive pulmonary disease (COPD) and other respiratory diseases. TD-4208 has shown positive top-line results in COPD patients in multiple Phase 2 studies, and the FDA recently agreed to the design of the Phase 3 registrational program, which is anticipated to begin this year. Under the terms of the agreement, Mylan and Theravance Biopharma will co-develop nebulized TD-4208 for COPD and other respiratory diseases. Theravance Biopharma will lead the U.S. registrational development program and Mylan will be responsible for reimbursement of Theravance Biopharma\'s costs for that program up until the approval of the first new drug application, after which costs will be shared. In addition, Mylan will be responsible for commercial manufacturing. In the U.S., Mylan will lead commercialization and Theravance Biopharma will retain the right to co-promote the product under a profit-sharing arrangement. Outside the U.S. (excluding China ), Mylan will be responsible for development and commercialization and pay Theravance Biopharma a royalty on net sales. Theravance Biopharma retains worldwide rights to TD-4208 delivered through other dosage forms, such as a metered dose inhaler or dry powder inhaler (MDI/DPI). In September 2014 , Theravance Biopharma announced positive top-line results from its Phase 2b dose-ranging study of TD-4208. TD-4208 met the primary efficacy endpoint (change from baseline in trough FEV1 [forced expiratory volume in one second] following the last dose on Day 28) with statistically significant responses at once-daily doses of 88, 175 and 350 mcg. The lowest dose of 44 mcg once-daily produced a sub-therapeutic response that was not statistically different from placebo. In November 2014 , Theravance Biopharma announced positive top-line results from the once- versus twice-daily (QD versus BID) study of TD-4208. The study compared 175 mcg once-daily against 44 mcg twice-daily in a 3-period, 7-day placebo-controlled crossover study conducted in 64 COPD patients. The study met its primary endpoint and demonstrated that the lower dose (44 mcg) administered twice-daily did not produce greater bronchodilation than the higher dose (175 mcg) administered once-daily. The frequency of adverse events was low and consistent across all three treatments including placebo. There was one death in the study that was assessed by the study investigator as unrelated to study medication.
Mylan and Theravance Biopharma believe that TD-4208 has the potential to be the only FDA -approved once-daily nebulized LAMA product for COPD patients in the near term and it may offer longer-term opportunities for combination with other nebulized products. In addition, the patent portfolio for TD-4208 is currently expected to provide a TD-4208 nebulized product with exclusivity in the U.S. until at least 2025, which does not include any potential patent term extensions. Given the short- and long-term potential of this differentiated product, and in an effort to optimize its uses of capital, Mylan has decided to redeploy resources from the development of its combination nebulized ICS/LABA product (Combo) to TD-4208.
Financial terms: In addition to funding the U.S. registrational development program, Mylan will pay Theravance Biopharma an initial payment of $15 million in cash and has agreed to make a $30 million equity investment in Theravance Biopharma by purchasing newly issued Ordinary Shares at a price of $18.92 per share, which is equal to a 10% premium over the 5-day trailing volume-weighted average price ending January 30 . Under the terms of the agreement, Theravance Biopharma is eligible to receive potential development and sales milestone payments totaling $220 million in the aggregate, with $175 million associated with TD-4208 monotherapy and $45 million for future potential combination products
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