Covis Pharma’s statement to The Times about Makena

The next combines a number of statements from Covis Pharma despatched by way of e mail. It has been organized for readability.

Covis Pharma’s response:

Makena is the one FDA-approved remedy to cut back the chance of preterm beginning in ladies with a historical past of spontaneous preterm beginning and its security profile for the mom and child are properly established. As such, Covis is concentrated on extra analysis to additional show the efficacy of Makena and to protect continued, inexpensive entry for indicated sufferers.

The present regulatory standing pertains particularly to conflicting efficacy information, because the product’s security was confirmed in each the unique scientific trial [known as the Meis trial] that resulted within the accelerated approval and within the subsequent confirmatory trial.

17P is the one FDA-approved class of branded and generic remedies to assist forestall the chance of preterm beginning in ladies with a historical past of spontaneous preterm beginning, and the totality of information on 17P and the branded model Makena helps its continued constructive benefit-risk profile and the necessity for continued affected person entry.

On condition that Makena quickly grew to become the usual of care within the U.S. following its approval primarily based on the outcomes of the Meis trial, it grew to become infeasible to enroll high-risk sufferers within the U.S. in a placebo-controlled confirmatory scientific trial. It was due to this fact essential to enroll sufferers outdoors of the U.S. within the confirmatory trial, referred to as PROLONG. Consequently, the demographics of enrolled sufferers in PROLONG had been considerably completely different from these enrolled within the U.S.-based Meis trial, together with an total decrease danger of preterm beginning (in each the placebo and remedy arms).

Extra particularly, Meis enrolled 59% U.S. black ladies whereas PROLONG solely enrolled 6.6% U.S. black ladies. PROLONG affected person inhabitants was overwhelmingly made up of white European ladies. The relevance of the distinction in demographics is the social determinants of well being and due to this fact the completely different degree of preterm beginning danger every group could also be topic to.

Whereas each trials demonstrated a constructive security profile for 17P, Meis — which had a various, U.S.-based participant inhabitants — and PROLONG — which had an overwhelmingly white, lower-risk European participant inhabitants — confirmed completely different efficacy outcomes.

In 2020, preterm beginning and its issues had been the second-largest contributor to toddler dying throughout the nation, disproportionately affecting folks of shade who’re regularly underrepresented in scientific research.

We’re dedicated to serving to suppliers and indicated sufferers entry Makena and the Makena Care Connection helps sufferers by connecting eligible sufferers to prescription assist and monetary help. Since 2018, ~115,000 sufferers have been directed to Makena Care Connection by their physicians. As well as, beneath Covis’ possession, Covis has diminished the web worth of Makena for its payer and state purchasers, which is reflective of Covis’ dedication to creating Makena accessible to at-risk sufferers.

We observe that the $700 worth per dose isn’t correct and the precise worth per dose for many payers and states is considerably much less.

Covis has urged the FDA to permit for additional research throughout the U.S. well being care system to grasp which, if any, populations could profit most from 17P. We’re happy that the FDA has granted our request for a listening to to deal with these crucial points.

Covis is unable to touch upon actions carried out by AMAG Prescribed drugs previous to Covis’ possession, together with any feedback made on the FDA Advisory Committee assembly in 2019.

Concerning the research by the Public Well being Institute in Oakland that discovered a most cancers danger: Excluding the formulation, this research affords no comparability to Makena, the one FDA-approved remedy to cut back the chance of preterm beginning in ladies with a historical past of singleton spontaneous preterm beginning, nor does it distinguish between an earlier model of the drug launched within the Nineteen Fifties to deal with a distinct affected person inhabitants for a distinct goal. Present scientific steering stays unchanged, as famous by the American School of Obstetricians and Gynecologists, which has acknowledged that “as a consequence of limitations within the design, the research’s findings usually are not conclusive and shouldn’t affect observe.”

We are able to additionally refer you to the next supplies for extra background on 17P:

• “Position of progestogens in ladies in danger for spontaneous preterm beginning: the ultimate phrase?” Ibrahim SA, Haas DM. Lancet; 397:1158-1159. (2021)

• “Security evaluate of hydroxyprogesterone caproate in ladies with a historical past of spontaneous preterm beginning” Sibai B, Saade GR, AF Das AF, Gudeman J. J Perinatol. (2020)

• “Re-examining the Meis Trial for Proof of False-Constructive Outcomes” Sibai B, Saade GR, Das AF. Obstet Gynecol; 136(3):622-627. (2020)

• ACOG Assertion on 17p Hydroxyprogesterone Caproate (2019)

• “17-OHPC to Forestall Recurrent Preterm Start in Singleton Gestations (PROLONG Examine): A Multicenter, Worldwide, Randomized Double-Blind Trial” Blackwell SC et al. J Perinatol; 37(2):127-136. (2019)

• “4-12 months follow-up of youngsters uncovered to 17alpha hydroxyprogesterone caproate (17P) in utero” Northern A. Am J Obstet Gynecol; 195(6,56). (2006)

• “Prevention of Recurrent Preterm Supply by 17 Alpha-Hydroxyprogesterone Caproate” Meis PJ et al., N Engl J Med; 348:2379-2385. (2003)