Krystal Biotech (KRYS) : First gene therapy for skin

• The first gene therapy that can be applied to the skin was able to heal the blistering wounds endured by children with a structural skin deficiency. In addition to being the first topical gene therapy, the treatment from Krystal Biotech would be the first gene therapy that can be repeated because it doesn’t trigger an immune response.

 

 

 

 

Krystal Biotech announces positive topline results from GEM-3 pivotal trial for VYJUVEK for treatment of dystrophic Epidermolysis Bullosa

The primary endpoint of the trial evaluated complete wound healing of topical VYJUVEKTM compared to placebo at six-month timepoints and met statistical significance. VYJUVEKTM is the first non-invasive, topical and redosable gene therapy in development, and the only genetically corrective approach to treat dystrophic EB that has successfully completed a double blinded Phase 3 trial.

• 31 patients (31 primary matched-wound pairs) were enrolled and evaluable for safety and efficacy per the primary intent-to-treat (ITT) analysis.
• 67% of wounds treated with VYJUVEKTM achieved the primary endpoint of investigator assessed complete wound healing at the six-month timepoints as compared to 22% of wounds treated with placebo.
• 71% of wounds treated with VYJUVEKTM achieved the secondary endpoint of investigator assessed complete wound healing at the three-month timepoints as compared to 20% of wounds treated with placebo.
• In an ad-hoc analysis, the trial also demonstrated a statistical difference between the active and placebo groups for wounds that demonstrated complete wound healing at both the three- and six-month timepoints .
• VYJUVEKTM was well tolerated. No drug-related serious adverse events or discontinuations due to treatment were reported. One mild drug-related adverse event was reported during the trial.
• The immunogenicity profile of VYJUVEKTM (as measured by anti-HSV-1 and anti-COL7 antibodies) was consistent with the prior GEM-1/2 study where we observed no meaningful change in anti-HSV-1 or anti-COL7 antibodies.

Based on these results, Krystal intends to file a Biologics License Application (BLA) with the U.S. Food and Drug Administration (FDA) in the first half of 2022 as the first step in executing its global regulatory and commercialization strategy to bring this investigational therapy to patients in need. The Company expects to submit a Marketing Authorization Application (MAA) in Europe shortly after the BLA. Exploration of the potential regulatory path forward in other geographies, including Japan, is underway. Krystal will continue to manufacture VYJUVEKTM using the commercial scale process at its in-house cGMP manufacturing facility, ANCORIS, which was designed to support potential launch. The Company is currently constructing its second, larger, facility ASTRA, which is expected to come on-line in 2022 to help support a potential global launch and the pipeline.

-= Sarepta Therapeutics (SRPT) : Disappointing gene-therapy study results

 

Sarepta Therapeutics announces top-line results for Part 1 of Study 102; primary functional endpoint did not achieve statistical significance

Sarepta Therapeutics today announced top-line results from Part 1 of Study SRP-9001-102 (Study 102), an ongoing, randomized, double-blind, placebo-controlled clinical trial to evaluate the safety, efficacy, and tolerability of a single dose of SRP-9001 in 41 patients with Duchenne muscular dystrophy.

• SRP-9001 is an investigational gene transfer therapy intended to deliver its micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein.

At 12 weeks post-treatment compared to baseline, the study met its primary biological endpoint of micro-dystrophin protein expression.

• Participants who received SRP-9001 had mean micro-dystrophin expression of 28.1%, as measured by western blot.
• Accompanying secondary biological endpoints including vector genome copies per nucleus, percent positive fibers, intensity, and reduction in creatine kinase (exploratory) were also met.

In the primary functional endpoint, SRP-9001-treated participants showed an increase in NSAA total score compared to placebo at 48 weeks; however, the difference was not statistically significant.

• At every time point measured, the cohort of SRP-9001 treated participants outperformed the placebo group, and, at 48 weeks, participants in the treatment group demonstrated a statistically significant increase of 1.7 points in NSAA total score compared to baseline, while participants in the placebo group saw an increase of 0.9 points on the NSAA total score compared to baseline, which was not statistically significant.

In the pre-specified analysis by age-group, by which the randomization was stratified, participants aged 4-5 years at time of treatment with SRP-9001 demonstrated a statistically significant improvement in NSAA total score versus the age-matched placebo cohort, achieving a 4.3-point improvement on NSAA at 48 weeks post-treatment from baseline.

The results from Study 102 reinforce the "favorable" safety and tolerability profile of SRP-9001, with no new safety signals identified.

-=Sarepta Therapeutics (SRPT) : positive results with Duchenne Muscular Dystrophy drug

Sarepta Therapeutics announces that at its first R&D Day, Jerry Mendell, M.D. presented positive preliminary results from the first three children dosed in the Phase 1/2a gene therapy micro-dystrophin trial to treat patients with Duchenne Muscular Dystrophy 

At the Company's R&D Day, Jerry Mendell, M.D. of Nationwide Children's Hospital presented positive preliminary results from its Phase 1/2a gene therapy clinical trial assessing AAVrh74.MHCK7.micro-Dystrophin in individuals with Duchenne muscular dystrophy (DMD). Dr. Mendell presented the following preliminary data on the first three patients enrolled in the study:

• All patients showed robust expression of transduced micro-dystrophin, which is properly localized to the muscle sarcolemma, as measured by immunohistochemistry. Mean gene expression, as measured by percentage of micro-dystrophin positive fibers was 76.2% and the mean intensity of the fibers was 74.5% compared to normal control.
• All post-treatment biopsies showed robust levels of micro-dystrophin as measured by Western blot, with a mean of 38.2% compared to normal utilizing Sarepta's method, or 53.7% compared to normal pursuant to Nationwide Children's quantification of Sarepta's method that adjusts for fat and fibrotic tissue.
• A mean of 1.6 vector copies per cell nucleus was measured in patients, consistent with the high micro-dystrophin expression levels observed.
• All patients showed significant decreases of serum creatine kinase (CK) levels, with a mean reduction of CK of over 87% at Day 60. CK is an enzyme associated with muscle damage and patients with DMD uniformly exhibit high levels of CK. Indeed, significantly elevated CK is often used as a preliminary diagnosis tool for DMD, which is then followed by confirmatory genetic testing.
• No serious adverse events (SAEs) were observed in the study. Two patients had elevated gamma-glutamyl transferase (GGT) that resolved with increased steroids within a week and returned to baseline levels. There were no other significant laboratory findings. Patients had transient nausea generally during the first week of therapy coincident with increased steroid dosing.
• Peers: PTCT -6% and SLDB +16%.

=AveXis (AVXS) to be acquired by Novartis (NVS) for $218/share

• Novartis agreed to acquire Chicago-area company AveXis for $8.7 billion to gain a promising drug to treat a rare disease that afflicts infants, hastening a shift toward gene therapy and precision medicines.
• AveXis, incorporated in 2010, sold shares in an initial public offering in 2016 at $20 a share. CEO Sean Nolan is a former executive at InterMune and Ovation Pharmaceuticals.
• The transaction is Novartis' second deal to advance in gene therapy this year—and the first led by new CEO Vas Narasimhan. The Swiss drugmaker is redeploying some of the $13 billion in proceeds from the sale of its stake in a consumer-health joint venture to partner GlaxoSmithKline to gain more firepower in prescription medicines before some of its existing best-sellers lose patent protection.
• AveXis is developing a product to treat spinal muscular atrophy, an inherited neurodegenerative disease caused by a defect in a single gene, which shows the potential to become a blockbuster, according to Novartis.
• Roche Holding and Biogen are other drugmakers that may be interested in acquiring the U.S. company, Biren Amin, an analyst for Jefferies in New York, said in a report.
• AVXS-101 helped a small group of babies with spinal muscular atrophy hit development milestones at a rate previously unseen, a study showed in November. The first medication for the disease, Biogen's Spinraza, won approval less than a year ago. Babies with the most severe form of the disease typically die before age two.
• The first gene therapy approved in Western Europe, UniQure's Glybera, turned out to be a flop. The company withdrew it from the market last year and is shifting its focus to hemophilia treatments.

• AVXS +81.23%, BOLD +9.57%, ADVM +7.25%, ABEO +7.14%, CRSP +5.27%, NTLA +5.04%, SGMO +4.42%, BLUE +4.39%, VYGR +3.34%, EDIT+3.01%, IONS +1.77%, ONCE +1.60%, ALNY +1.13%; other gene therapy stocks: QURE, SELB, AGTC, NITE

AveXis to be acquired by Novartis (NVS) for $218/share in cash, or approximately $8.7 bln 

AveXis has several ongoing clinical studies for the treatment of spinal muscular atrophy (SMA), an inherited neurodegenerative disease caused by a defect in a single gene, the survival motor neuron (SMN).

• Assuming mid 2018 completion, the acquisition impact would be slightly negative to Core Operating Income in 2018 and 2019, mainly due to R&D investments. As of 2020, Novartis would expect the acquisition impact to strongly contribute to Core Operating Income and Core EPS accretion driven by a significant increase in sales.
• Novartis is permitted under specified antitrust related circumstances to extend the Outside Date to October 6, 2018. If Novartis elects to extend the Outside Date, the offer price will increase from $218 per share to $225 per share in cash.

Completion of the transaction is expected in mid-2018, pending the successful completion of the tender offer and all other closing conditions.