Replies to post #103985 on Biotech Values

[DewDiligence]

NVS Reports Positive Phase-3 Menveo Data in Infants

[Menveo, a vaccine for meningococcal disease types A, C, Y and W-135, is currently approved in the US and EU for age 11-55 (#msg-46901962). The new data should allow a label expansion to the medically important infant group (age 2 months to 2 years), and NVS plans to submit data later for age 2-11. Though unlikely to be a blockbuster, Menveo figures to be a nice midsized product for NVS. (Menactra, a similar product from SNY that is not approved for infants, sells $600M annually.) Note: Menveo is distinct from NVS’ 4CMenB vaccine for type B meningococcal disease (#msg-54312729).]

http://www.novartis.com/newsroom/media-releases/en/2010/1454719.shtml

›October 25, 2010 07:15 CET

• New pivotal phase III data show Menveo induced immune responses in a high percentage of infants against four important meningococcal disease-causing serogroups

• The highest rates of meningococcal disease, a sudden, serious and often deadly disease, occur early in the first year of life

• Menveo has the potential to be the first meningococcal quadrivalent conjugate vaccine that induces high levels of protective antibodies in infants vaccinated from 2 months of age

Basel, October 25, 2010 - New Phase III data indicate that Menveo (Meningococcal Group A, C, W135 and Y conjugate vaccine) demonstrated robust immunogenicity in infants potentially offering protection against four major serogroups of meningococcal disease. These data were presented during an oral presentation at the 48th annual meeting of the Infectious Disease Society of America (IDSA) held in Vancouver, Canada.

This pivotal trial, including more than 4,500 infants worldwide, met its primary endpoints. Results show that a high percentage of infants vaccinated with four doses achieved robust immune responses against meningococcal serogroups A, C, W135 and Y. Menveo was generally well tolerated when given either alone or co-administered with other pediatric vaccines. Menveo has the potential to be the first meningococcal quadrivalent conjugate vaccine that induces high levels of protective antibodies against serogroups A, C, W135 and Y in infants vaccinated from 2 months of age. Infants under one year of age are at greatest risk for meningococcal disease and currently no broad-coverage vaccine is licensed for this population.

"In my practice I have seen the devastating effects of meningococcal disease in infants," said Stan Block, MD, FAAP, an investigator for the study. "Meningococcal vaccines are being developed that can provide broad protection against the disease in this vulnerable population."

Menveo has the potential to fulfill an unmet medical need as a vaccine that can help protect people, from early infancy to adulthood, against four major causes of meningococcal disease (serogroups A, C, W135 and Y) , a sudden, unpredictable and often life-threatening illness. Together these four serogroups cause the majority of meningococcal disease cases in the United States (US), Africa, and the Middle East and are also present in Europe, Asia and Latin America.

"As the most vulnerable age group, infants should be directly protected from this unpredictable and devastating disease," said Andrin Oswald, Division Head of Novartis Vaccines and Diagnostics. "These data are another step in the significant progress Novartis is making toward our goal of protecting all age groups against meningococcal disease."

In the US, Novartis intends to submit a supplemental Biologics License Application (sBLA) based on these pivotal data to the US Food and Drug Administration (FDA) by year-end. If approved, Menveo will be the only meningococcal quadrivalent conjugate vaccine that could be administered to infants 2 months of age and older. This label claim extension will be also submitted in Europe and in other parts of the world.

Menveo Clinical Trial Results and Design

The Phase III, randomized, open-label, multi-center, parallel-group study is the first to evaluate and present results for a meningococcal quadrivalent conjugate vaccine in infants. The study involved 4,545 healthy infants in trial sites throughout the US and Latin America. Only data from the US trial sites were presented at IDSA. Infants were randomized 2:1 to receive routine infant vaccinations (DTaP, IPV, HBV, Hib, pneumococcal) alone or together with Menveo at 2, 4, 6 and 12 months of age. The primary objectives of the study were to assess the safety and tolerability of four doses of Menveo when given alone or co-administered with routine infant vaccines and, in a subset, to assess the immune response to the vaccine.

The percentage of infants who achieved a protective immune response was 67 percent for serogroup A, 97 percent for serogroup C, and 96 percent for serogroups W135 and Y when measured at 7 months of age, one month after the third dose. One month after the fourth dose at 12 months of age, the percentages were 94 percent for serogroup A, 98 percent for serogroup C, and 100 percent for serogroups W135 and Y. The immune response was measured by the percentage of participants achieving serum bactericidal antibody titers >1:8, using human complement (hSBA). In addition, responses to routine infant vaccine antigens, when co-administered with Menveo, were generally similar, except for a slightly lower immune response to pneumococcal serotype 6B after the infant series.

When given alone, Menveo was well tolerated, with a reactogenicity and safety profile similar to routine infant vaccines. Co-administration of Menveo with routine infant immunizations neither resulted in increased frequency nor severity of systemic reactions or other safety events. The most common side effects in both groups were sleepiness, irritability, persistent crying, changed eating habits, rash, and gastrointestinal events. Rates of fever >38° C were similar in both groups with the majority of cases resolving within 24-48 hours. Incidence of serious adverse events was not different between the groups.‹

[DewDiligence]

Booster shot of NVS’ Bexsero (f/k/a 4cMenB) enhances efficacy in toddlers:

http://www.novartis.com/newsroom/media-releases/en/2011/1522283.shtml

This Phase III, open-label immunogenicity and tolerability extension analysis included more than 1,500 toddlers who had been administered a three-dose primary series of Bexsero at 2, 4, 6 months. Toddlers were randomized to receive either a fourth (booster) dose of Bexsero concomitantly with measles, mumps, rubella, and varicella vaccine (MMR-V), or Bexsero at 12 months followed by MMR-V at 13 months. Immunogenicity was measured using the hSBA assay and was assessed one month post booster dose.

This study met all primary endpoints. The data show Bexsero to be highly immunogenic in this age group against all vaccine antigens in all MenB strains tested (H44/76, 5/99, NZ98/254), with 11-19 fold increases in hSBA titers.

The PR above also reports data from two other Bexsero studies. Some analysts are predicting blockbuster status for this meningitis-B vaccine, which is a separate product from NVS’ Menveo.

[DewDiligence]

NVS reports additional Bexsero data in infants:

http://www.bloomberg.com/news/2012-02-07/novartis-s-bexsero-guards-infants-against-brain-swelling-malady-in-study.html

Bexsero is a meningococcal-B vaccine previously known as 4cMenB. As noted in #msg-54312729, there is no comparable product from any company, which is why NVS thinks it Bexsero can be a big seller.

[DewDiligence]

What makes a meningitis B vaccine especially challenging (author is head of vaccines at NVS):

http://the-scientist.com/2012/09/17/opinion-eliminating-meningitis/

The capsular polysaccharide of MenB cannot be used to create a universal vaccine because it has a chemical composition identical to a polysaccharide present in our body (polysialic acid), and is therefore not recognized as foreign by our immune system. MenB is the final frontier of meningococcal meningitis prevention.

To overcome this hurdle, Novartis researchers are using reverse vaccinology to develop our MenB candidate vaccine, Bexsero. We began exploring this technology in the late 1990s, after Craig Venter sequenced the first bacterial genome. We then began working with Venter to develop the process, which involves decoding the genetic makeup of a bacterium to predict the antigens that are likely to be on the surface of the bacteria. This approach provides instant access to entire antigen repertoire and allows fast identification even of those antigens that would be difficult or impossible by the conventional methods involving the time-consuming and expensive processes of growing the bacteria in culture and purifying their components. In the case of MenB, however, one of the antigens discovered by us was also identified by conventional approaches by scientists at Pfizer, and they are also using it to develop a MenB vaccine.

…Our MenB candidate vaccine was submitted for regulatory approval in Europe in December 2010, and Pfizer’s vaccine candidate continues to be vetted for safety and efficacy. I remain confident that in the future, we can eradicate meningococcal disease, including the elusive MenB, on a global level.

Note: NVS’ Bexsero was formerly known as 4MenB.