PTC Appeals Decision in Gunvalson Case

The blogging Drug and Device lawyers are now directly involved in the case of Gunvalson v. PTC Therapeutics, in which a teenager with muscular dystrophy is pursuing access to the biotech's experimental drug PTC124. Consequently they won't be commenting further on the case, but they will provide milestone legal docs, like PTC's opening brief in its appeal to Judge Martini's opinion (read background posts here and here).

PTC's brief is useful to the interested public, because it provides answers to several, previously unanswered questions about particulars in the case and specifically about the illness of the teenager, Jacob Gunvalson (which is now an open book, given the Gunvalson's suit against PTC).

For instance:

• Jacob has muscular dystrophy that is indeed characterized by a nonsense mutation (which causes a premature stop codon) in the gene encoding for dystrophin. Therefore the use of PTC124, which overrides the translation of stop codons, makes theoretical sense in the proposed treatment of Jacob's disease.
• Jacob's mother is a registered nurse.
• One outcome of PTC's 28-day phase 2a trial of PTC124 was the expression of dystrophin. Because patients with Becker muscular dystrophy (BMD) make limited amounts of dystrophin (unlike patients with Duchenne muscular dystrophy [DMD], who do not produce dystrophin), individuals with BMD were excluded from this trial.
• Jacob's Minnesota pediatrician, John Parkin, apparently requested access to PTC124 on behalf of Jacob. PTC's chief medical officer, Langdon Miller, evidently denied this request in a letter dated April 2006, "stating that no [emphasis in brief] access would be given outside of clinical trials until an appropriate time." Therefore Jacob's attempt to access PTC124 antedates his attempt to enroll in PTC's phase 2a trial of the drug (see below).
• Richard Finkel, CHOP neurologist and a principal investigator of the phase 2a trial, reviewed Jacob's medical records in late 2006 to determine the teenager's eligibility for enrollment. Jacob's records, as documented by his pediatrician (presumably Parkin), revealed an 8-year diagnosis of BMD, along with renal dysfunction and a "racing heart" (ie, tachycardia). Finkel evidently reviewed a "muscle biopsy," which was compatible with the diagnosis of BMD (It is not clear if the biopsy report or the actual biopsy specimen was reviewed by Finkel). Jacob was denied enrollment in the phase 2a trial, not only on the basis of his BMD diagnosis, but also as a result of his renal impairment and cardiac condition. Therefore Jacob and his parents did not forgo enrollment in the phase 2a trial on the advice of PTC vice president Claudia Hirawat, as previously indicated; Jacob was ineligible for trial enrollment.
• Jacob's mother sent e-mails to Hirawat on January 30, 2007, expressing deflation at Finkel's decision and indicating that she knew Jacob produced dystrophin, which precluded his phase 2a trial enrollment. Also in December 2006, Jacob's mother sent an e-mail to Hirawat expressing concern that Jacob might receive placebo should he be enrolled in another PTC124 trial (the phase 2a trial was not placebo controlled).
• Jacob became nonambulatory in March 2007, a condition that precluded enrollment in PTC's phase 2b trial of PTC124.
• In May 2007, Cincinnati child neurologist and principal investigator Brenda Wong concluded that Jacob had DMD after a "comprehensive medical evaluation." Her examination, which presumably included a review of Jacob's medical records, also confirmed his history of tachycardia (although there is no mention in the brief of her acknowledgement of his previously noted renal impairment). The timing of Wong's review is interesting, because it suggests that Jacob may still have been attempting to enroll in the phase 2a trial of PTC124 (via Wong) after being rejected for enrollment by Finkel. Addendum: Jacob's recent confinement to a wheelchair probably contributed to Wong's opinion that Jacob had the more severe diagnosis of DMD, in contradistinction to the previous diagnosis of BMD.

The strong subtext of the PTC brief is that Jacob's mother, in understandable desperation, likely heard what she wanted to hear from a number of PTC employees regarding her son's potential access to PTC124. What is evident is that she was concerned about (and wanted to avoid) the possibility that Jacob might receive placebo in a controlled trial of the agent. The brief also implies that Jacob's pediatrician, Parkin, possibly boosted the Gunvalson's unfounded hopes for access to PTC124.

It's a disheartening case all around, but so is every case portending a premature death.

And as the brief argues, Jacob's access to PTC124 would be "monumentally unfair" to those children in PTC's phase 2b trial, who risk the chance of receiving placebo for the sake of advancing medical science.