Key events in the development of PsA-TT, a new meningococcal conjugate vaccine

Transcription

1 Key events in the development of PsA-TT, a new meningococcal conjugate vaccine Meningi's Vaccine Project Closure Conference Addis Abeba, Ethiopia, February 22, 2016 F Marc LaForce, MD Serum InsCtute of India Pvt. Ltd.

2 Three pivotal events The Meningi)s Vaccine Project becomes a virtual vaccine company in March 2002 A new conjuga)on method is transferred from FDA/NIH to Serum Ins)tute in December 2003 Serum Ins)tute successfully accepts tech transfers and scales up produc)on from laboratory to commercial scale (04-07) and licenses a new PsA-TT vaccine, MenAfriVac (2009)

3 Availability of Group A Meningococcal Vaccines for Sub-Saharan Africa in 2001 Only polysaccharide A vaccines were available and they were used in reac)ve campaigns Over 100 million doses of A/C PS vaccine were purchased by meningi)s belt countries from The reac)ve campaigns were expensive, largely ineffec)ve, but poli)cally necessary. There were no plans to develop meningococcal A conjugate vaccines for Africa.

4 CreaCon of the MeningiCs Vaccine Project The terrible meningi)s epidemic in 1996 lead African public health officials to ask WHO to help them address this problem. Interna)onal mee)ngs organized by WHO in 2000 and 2001 recommend that conjugate meningococcal vaccines be developed for Africa. An informal collabora)on between PATH, WHO and CDC/Atlanta further assess the problem. In June 2001 the Meningi)s Vaccine Project (MVP) is created with Gates Founda)on support as a 10 year partnership between WHO and PATH. Goal: to eliminate epidemic meningi's in Africa as a public health problem through the development, tes'ng, licensure, and widespread use of conjugate meningococcal vaccines

5 Informing African partners while beler understanding the problem Fall 2001 MVP discussions with African public health officials and WHO/AFRO (Harare, Niger, Burkina Faso, Nigeria) yielded consistent informa)on Cost of vaccine was the most important limi)ng factor to the introduc)on of new vaccines in Africa Meningi)s belt countries are among the poorest in the world Success of MVP (widespread use of a conjugate meningococcal vaccine in mass campaigns) would not be possible unless vaccines were priced less than $US 0.50 per dose

6 Early pressures in 2001 Discussions with Pharma had already begun with WHO in 2000 and WHO/PATH in early General expecta)on that MVP would nego)ate a contract with a mul)na)onal for the development of an A/C conjugate vaccine

7 Product development with established vaccine manufacturers MVP Provides funds and monitors Vaccine company Development, production, regulatory, clinical, fill/finish Finished Product

8 MVP negocacons with Pharma (01-02) Mee)ngs with Chiron, Baxter and GSK (September 2001 March 2002) Key issues in the nego)a)ons included: Vaccine price Guaranteed purchase (effect of volume on price) Investments to increase manufacturing capacity Crea)ng a no risk model

9 MVP becomes a virtual vaccine company March 2002 MVP could not reach an agreement with major vaccine manufacturers and nego)a)ons end in March 02 Acer consulta)ons with MVP Technical and Management Commidees and the Gates Founda)on, MVP elects to become a virtual vaccine company with the goal of developing a Group A conjugate vaccine. Crucial elements in making this decision included Inputs from African public health officials on the importance of vaccine price Availability of a business plan commissioned by Teresa Aguado and Luis Jodar at WHO indica)ng that cost of goods for making million doses of a Men A conjugate vaccine could be as low as $US 0.18 per dose. Input from four consultants, Costante Ceccarini, Jean Petre, Art Elliot and Dan Granoff whose opinions were highly valued.

10 MVP product development plan Contract manufacturer PsA and TT Tech transfer MVP Funding, technology development Tech transfer Developing country manufacturer Scale up, fill finish Clinical and regulatory Licensed vaccine

11 Challenges and opportunities with new development model Challenges Greater risk More complex technical and managerial issues Identifying technology Technology transfer Clinical trials Changes in Nm epidemiology Non A meningitis Bivalent product Opportunities Low vaccine cost IPR issues straightforward Opportunity cost issue resolved Tailor-made vaccine for Africa Strengthens developing country capacity Model for other vaccines

12 ConjugaCon of PSA to carrier protein SynCo BioPartners, a contract manufacturer from Amsterdam, chosen as a PSA manufacturer TT selected as the preferred carrier protein Iden)fying a conjuga)on method to prepare a PsA-TT conjugate vaccine Pharma uninterested in sharing/sublicensing IP In June 2002 MVP began working with European biotech company with extensive experience developing PS conjugate vaccines

13 Emerging vaccine manufacturers expressing interest and visited BioFarma (Indonesia) BioManguinhos (Brasil) BirMex (Mexico) Finlay (Cuba) Serum Ins)tute of India (India)

14 Troubles with conjugacon IP (June 2003) Novel conjuga)on method developed by Biotech; test lots of PsA-TT (laboratory scale) made and successfully tested in mice At a UK mee)ng in March 2003 the MVP Technical Advisory Group approved tech transfer of method to Serum Ins)tute in June The development Biotech partner withdrew from the project in June 2003.

15 Fallout from failed development partnership (Summer 2003) Major blow to the project Several vaccine experts opined We told you so these are only amateurs Open cri)cism of the project at July 2003 WHO SAGE Mee)ng Significant morale problems in the project Internal review at MVP in late June concluded that the development strategy was sound but that a poor partner choice had been made

16 Product development work restarted In July 2003 MVP requested proposals from 2 public laboratories and 4 vaccine manufacturers MVP received 4 proposals that were evaluated by the MVP Expert Panel in October 2003 No final recommenda)on made but two avenues were chosen for further evalua)on Transfer a conjuga)on method from CBER (FDA) to Serum Ins)tute of India Ask Baxter, a US-based Pharma company, to make bulk Men A conjugate for fill/finish at Serum Ins)tute.

17 FDA and the NIH step up Carl Frasch had indicated in May 2003 that a robust conjuga)on method for NmA had been developed by Robert Lee at CBER/FDA and was available Discussions with FDA begin in late June Much of the background work had already been done by Drs. Lee and Frasch Confirmatory tes)ng of the CBER/FDA vaccine was done by Dan Granoff in October He concluded this is the most potent Men A conjugate J had ever tested. Transfer formali)es were rapidly nego)ated at the NIH Office of Technology Transfer (P Soukas and C Odoson) Technology transfer to a Serum Ins)tute team began in Bethesda, MD during the 2003 Christmas holiday.

18 Serum InsCtute successfully accepts transfer of FDA conjugacon technology Preclinical lots of PsA-TT prepared in March 2004 Formal agreement between PATH and Serum Ins)tute signed in June of 2004 GMP produc)on is gradually scaled up Analy)c techniques developed A dedicated facility is built in Pune with costs shared between MVP and Serum Ins)tute

19 Product development decisions PsA-TT from Serum Ins)tute using the FDA conjuga)on method were tested at NIBSC (Poders Bar, UK) in November 2004 Results were reviewed and approved by MVP Expert Panel and WHO SAGE members in November 04 Go decision rendered Clinical trials of the PsA-TT vaccine begin in MenAfriVac is licensed by the Drugs Controller General of India in December 2009

20 Lessons learned PDP vaccine partnerships can solve important public health problems but the scien)fic base must be solid Expect cri)cism if you are doing something new Recognize and accommodate to cultural reali)es Choose consultants who are smart and candid but also have sound interpersonal skills The business model must be acceptable to all partners Face to face )me with partners is essen)al; when in doubt go visit Iden)fy and pay aden)on to the key players, work to understand what they want Be transparent and communicate, communicate, communicate

21 The Meningitis Vaccine Project The 2001 MVP values statement The project is about public health impact and not simply making vaccines available Decisions about candidate vaccines linked to introduc)on strategies and likely financial constraints African public health officials to be closely involved with MVP