AstraZeneca-BMS Diabetes Deal Done: What’s Next On Biocon’s Oral Insulin?

AstraZeneca has declined an option agreement from Bristol-Myers Squibb on Indian drug maker Biocon’s oral insulin, raising questions about the fate of the candidate Biocon hopes will be a blockbuster.

MUMBAI – AstraZeneca PLC has said it would not take responsibility for an option agreement signed by Bristol-Myers Squibb Co. to develop Biocon Ltd.’s oral insulin candidate coded IN-105. That decision brings into question the future development of a candidate the Indian firm sees as a potential blockbuster. BMS declined to respond to questions sent by PharmAsia News.

Notably, AstraZeneca’s decision in December to acquire BMS’ entire diabetes portfolio, signaled its keen interest to expand into the therapy. But at the time, neither BMS nor AstraZeneca shared details on future pipeline drugs including Biocon’s oral insulin (Also see "AZ Doubles Down On Diabetes, Buys Out Bristol’s Share in Alliance" - Pink Sheet, 19 Dec, 2013.).

Pipeline products listed by BMS include a Phase I metabolics compound coded PEG-FGF21 and Myalept (metreleptin) for generalized lipodistrophy in Phase III (Also see "FDA Panel Accepts Metreleptin For Generalized Lipodystrophy, No Further Criteria Needed" - Pink Sheet, 12 Dec, 2013.).

That apart, its marketed products include drugs like Forxiga (dapagliglozin), Onglyza (saxagliptin), Kombiglyze (saxagliptin/metformin XR), Symlin (pramlintide), Byetta (exenatide) and Bydureon (exanatide XR for injectable suspension).

Bet On Biocon Candidate Now In Doubt

For its part, BMS had bet on Biocon’s oral insulin in November 2012, and entered into an option agreement for its prandial oral insulin candidate IN-105.

“Under the terms of the agreement, Bristol-Myers Squibb will have the right to exercise an option to obtain an exclusive worldwide license to the program. Biocon will conduct clinical studies to further characterize IN-105's clinical profile according to a pre-agreed development program up to the completion of Phase II,” the Nov. 16, 2012, press release said.

If BMS exercises its option to license IN-105 following the successful completion of the Phase II trial, the company would assume full responsibility for the development program, including all development and commercialization activities outside India (Also see "BMS, Biocon Team Up To Rekindle Oral Insulin Hopes" - Scrip, 16 Nov, 2012.).

Biocon was to receive a license fee in addition to potential regulatory and commercial milestone payments and sales royalties on IN-105 outside India. Biocon would retain exclusive rights to IN-105 in India.

However, with the latest decision of BMS to part with its diabetes portfolio, the actual progress made on Biocon’s oral insulin molecule is not clear.

Biocon CEO Kiran Mazumdar Shaw told PharmAsia News that her plan to develop the product is on track and that she was awaiting the future direction on the product. A source said BMS had recently prepared for a clinical study on the product in the U.S., but clarification from sources on details of those plans and any progress, or lack thereof, was not available.

A Few Bright Spots

The website Clinicaltrials.gov, maintained by the U.S. National Institutes of Health, shows a (Phase I) study on oral insulin was initiated in December 2009. On the Indian clinical trials registry, data show Phase III clinical trials were conducted with 264 patients. The trial (Summary) said the study was planned to assess the safety and efficacy of post prandial oral insulin on diabetes control in patients with type 2 diabetes mellitus.

A senior researcher in the area of metabolics said Shaw may be encouraged to take the drug forward as there is “compelling evidence” that favors development of oral insulins and a renewed interest from big companies.

In fact, in October 2013, Novo Nordisk AS confirmed to Reuters that it would examine investments upwards of $3.7 billion through 2020 in developing insulin tablets as part of its newest approach to defend its traditional turf. A Novo Nordisk spokesperson estimated the oral diabetes market to be more than $18 billion by 2020.

Another company in the race to develop an insulin tablet is Israel’s Oramed Pharmaceuticals Inc. , which is in Phase II with its ORMD-801, while Novo has yet to enter Phase II (Also see "Tackling Oral Insulin: A Niche Development Space" - Pink Sheet, 1 Aug, 2011.).

Biocon In The Lead?

Industry sources still feel Biocon has a clear edge if a global race heats up, barring one drag when it failed to clear the Phase III India trials in 2011. The drug could not meet its primary endpoint of lowering HbA1c levels by 0.7% in the study. But Biocon said it had placed harsh conditions and there was a clear case for a review of the study design (Also see "Biocon's Oral Insulin Fails To Meet Primary Endpoint; Unfazed, Company Says Stage Set For Partnering Talks With Global Pharma" - Scrip, 11 Jan, 2011.).

Industry sources also said one question is whether BMS saw bright chances of success for the drug and decided not to include Biocon’s oral insulin in the agreement with AstraZeneca. But there has been no clarity on that speculation from the companies or sources and experts suggest the pendulum could swing either way.

A biotech M&A expert said in exceptional cases higher interest may be seen in pursuing a single program and following a generation of strong clinical data, paving the way for the candidate to potentially return larger paybacks and gain the interest of partners to share costs.

Another alternative under speculation is whether BMS exercises its option and hands back the drug to Biocon if the agreement provides clauses for transfer of rights back to the original owner of the drug for a higher premium.

“The negative side may be that AstraZeneca may have shown unwillingness to take up the development rights primarily due to the risks attached with developing a product that has no clear precedence of success,” the same expert said, declining to be named.

Biocon, which also collaborates with BMS on preclinical drug discovery projects through its CRO arm Syngene, may be open to taking the drug back as its prospective candidate.

Biocon’s Shaw has said that once developed, the product has the potential to significantly alter the paradigm of diabetes disease management.

BMS has been a close ally for Biocon. Through its partnership signed with Biocon’s Syngene in 2007, BMS has strengthened its drug discovery and development capabilities.

In 2009, the two companies inaugurated a dedicated research establishment further bolstering their research association. A decision on the future development of oral insulin may be an important turning point for the two companies (Also see "After 10-year Partnership, Biocon’s Syngene, Bristol-Myers Squibb Establish Largest Research Center In Asia" - Scrip, 23 Mar, 2009.).